An anti-infective pharmaceutical composition, its preparation method and application

Abstract

The invention belongs to the field of pharmaceutical preparation technology, and specifically relates to an anti-infective pharmaceutical composition, a preparation thereof, a preparation method thereof and an application thereof. The pharmaceutical composition of the invention comprises the following components: bifonazole, quercetin, matrine, natamycin, 2% iodine tincture and ethanol. The pharmaceutical composition of the invention combines bifonazole with quercetin and matrine, and through the synergistic coordination between the components of bifonazole, quercetin and matrine, has the advantages of strong antibacterial activity, wide antibacterial spectrum, wide range of indications, low toxicity and side effects, and is not easy to cause the body to produce drug resistance. The pharmaceutical composition of the invention belongs to non-antibiotic and non-hormone preparations, has simple components, and is easy to obtain raw materials, and overcomes the defects of slow wound healing, incomplete treatment, easy recurrence, etc. of traditional pharmaceutical preparations, and has a simple preparation process, which is suitable for wide production and application.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine preparation, and specifically relates to an anti-infection medicine composition, a preparation thereof, and a preparation method and application thereof. Background Art

[0002] There are many drugs for treating infections caused by pathogenic microorganisms such as bacteria and viruses, and each has its own indications and application characteristics. Bifonazole is one of the drug ingredients that has been studied and reported. Bifonazole is an imidazole derivative with a broad antibacterial spectrum and has an inhibitory effect on 90% of pathogenic fungi. It can inhibit a variety of skin fungi (such as Trichophyton and Microsporum), yeasts (such as Candida, Flask-shaped yeast, and Toruloplasma glabrata), molds (such as Aspergillus) and various fungi (such as Coccidioides, Blastomyces, and Histoplasma). It also has activity against certain Gram-positive bacteria (such as Staphylococcus, Streptococcus, etc.).

[0003] At present, the treatment of fungal infections mainly uses oral antibiotics. Pure Western medicine preparations account for a large proportion of oral preparations, and Chinese medicine preparations are rare. After years of clinical application, the shortcomings of Western medicine preparations have gradually emerged. For example, the treatment principle for dermatophytosis and its secondary infectious diseases is mainly "oral sensitive antibiotics, topical berberine solution 1:2000 wet compress, and then topical Leifan paste, zinc oxide oil plus chloramphenicol, mupirocin cream and other antibiotic preparations, and antifungal preparations after the infection is controlled". The long treatment process and long-term and extensive use of antibiotics are extremely unfavorable to patients and do not conform to the principles of antibiotic use. Clinical treatment results have shown that specific anti-infective drugs are difficult to cure stubborn infections such as bacteria and fungi. Long-term inability to heal the infected area and repeated attacks will lead to mixed infections of multiple pathogens. There is basically no specific drug for stubborn diseases caused by mixed infections of two or more pathogens.

[0004] Chinese invention patent CN1254242A discloses an anti-infective drug composition and its pharmaceutical use. The composition is composed of an antifungal component and an antibacterial component, especially including bifonazole and chlorhexidine. The anti-drug composition provided by the invention can be used as an external medicine. Compared with ordinary external antibacterial drugs, it has a wider treatment range and is clinically used in the treatment of superficial fungal and bacterial infections of the skin, syphilis spirochete infections, onychomycosis, athlete's foot and other infectious diseases. It has the characteristics of high efficacy, low recurrence rate, low toxicity, etc.

[0005] Another Chinese invention patent CN1739507A discloses a pharmaceutical composition for treating mixed infectious diseases. The compound anti-infective pharmaceutical composition of the invention contains at least metronidazole, bifonazole and chlorhexidine acetate as main drug components, and preferably the mass ratio of metronidazole, bifonazole and chlorhexidine acetate is 1-10:10-1:1-10. It can effectively treat mixed infectious diseases, especially effectively treat mixed infectious vaginitis, liver abscess and the like caused by multiple pathogens, and amoebiasis and acute and chronic amoebic dysentery.

[0006] The shortcomings of the above-mentioned pharmaceutical compositions are that they all combine bifonazole with chemical drugs to treat infectious diseases. The effects are obvious in the short term, but they have certain effects on the body, some people will cause some side effects after taking the medicine, the disease recurrence is high, the raw material cost is high, and the preparation process is relatively complicated.

[0007] In view of this, there is an urgent need in the art for an anti-infective pharmaceutical composition that can solve the above-mentioned technical problems. Summary of the invention

[0008] In view of the problems existing in the prior art, the present invention provides an anti-infective pharmaceutical composition, a preparation thereof, a preparation method thereof and an application thereof.

[0009] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0010] An anti-infection pharmaceutical composition comprises the following components: bifonazole, quercetin, matrine, natamycin and 2% iodine tincture and ethanol.

[0011] Preferably, the composition comprises the following components by weight: 0.1-10 parts of bifonazole, 2-10 parts of quercetin, 2-10 parts of matrine, 0.02-0.04 parts of natamycin, 30-50 parts of 2% iodine tincture, and 150-200 parts of ethanol.

[0012] More preferably, the composition comprises the following components by weight: 3-6 parts of bifonazole, 5-8 parts of quercetin, 5-8 parts of matrine, 0.02-0.03 parts of natamycin, 35-45 parts of 2% iodine tincture, and 170-190 parts of ethanol.

[0013] More preferably, the composition comprises the following components by weight: 4 parts of bifonazole, 6 parts of quercetin, 6 parts of matrine, 0.03 parts of natamycin, 40 parts of 2% iodine tincture, and 180 parts of ethanol.

[0014] Preferably, the volume concentration of the ethanol is 75-85%.

[0015] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition, comprising the following steps: firstly, by weight, ultrasonically mixing bifonazole, quercetin, matrine and ethanol to obtain solution 1; then, mixing natamycin and 2% iodine tincture to obtain solution 2; and finally, mixing solution 1 and solution 2 evenly to obtain the pharmaceutical composition.

[0016] The present invention also provides an anti-infection preparation, comprising the above-mentioned pharmaceutical composition or the pharmaceutical composition prepared by the above-mentioned preparation method.

[0017] Preferably, the preparation is in the form of a solution.

[0018] The present invention also provides the use of the above-mentioned pharmaceutical composition or the pharmaceutical composition prepared by the above-mentioned preparation method or the above-mentioned anti-infection preparation in the preparation of drugs for preventing and treating bacterial infectious diseases.

[0019] Preferably, the bacterial infectious disease includes dermatophytosis.

[0020] Preferably, the pathogens include at least one of Staphylococcus aureus, Staphylococcus haemolyticus, Escherichia coli, Streptococcus, Enterococcus faecalis and Candida albicans.

[0021] Preferably, the dermatophytosis comprises at least one of tinea manuum, tinea corporis, tinea unguium and tinea capitis.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] (1) The pharmaceutical composition of the present invention combines bifonazole with quercetin and matrine. Through the synergistic cooperation among the components of bifonazole, quercetin and matrine, the composition has the advantages of strong antibacterial activity, a wide spectrum of antibacterial bacteria, a wide range of indications, low toxic and side effects, and is not easy to cause the body to develop drug resistance. It can effectively prevent and treat bacterial infectious diseases such as dermatophytosis and its secondary infectious diseases.

[0024] (2) The pharmaceutical composition of the present invention is a non-antibiotic and non-hormone preparation with simple components and readily available raw materials. It overcomes the defects of traditional pharmaceutical preparations such as slow wound healing, long treatment time, incomplete treatment, easy recurrence and narrow scope of application. The preparation process is simple and suitable for wide production and application. DETAILED DESCRIPTION

[0025] It is worth noting that the raw materials used in the present invention are all common commercially available products, among which quercetin, purity HPLC ≥ 98%, was purchased from Shanghai Yuanye Biotechnology Co., Ltd.; matrine, purity 98%, was purchased from Aladdin; Escherichia coli (CICC 10389), hemolytic Staphylococcus (ATCC 29970), Streptococcus (CICC B0182) and Candida (ATCC 2091) were all purchased from China Industrial Microbiological Culture Collection Management Center.

[0026] Example 1

[0027] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 4 parts of bifonazole, 6 parts of quercetin, 6 parts of matrine, 0.03 parts of natamycin, 40 parts of 2% iodine tincture, and 180 parts of ethanol with a volume concentration of 80%.

[0028] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, bifonazole, quercetin, matrine and ethanol with a volume concentration of 80% are ultrasonically mixed according to weight, and the ultrasonic power is set to 80W, the ultrasonic time is 0.5h, and the ultrasonic temperature is 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are mixed evenly to obtain the composition.

[0029] Example 2

[0030] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 0.1 parts of bifonazole, 2 parts of quercetin, 2 parts of matrine, 0.02 parts of natamycin, 30 parts of 2% iodine tincture, and 150 parts of ethanol with a volume concentration of 75%.

[0031] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, bifonazole, quercetin, matrine and ethanol with a volume concentration of 80% are ultrasonically mixed according to weight, and the ultrasonic power is set to 80W, the ultrasonic time is 0.5h, and the ultrasonic temperature is 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are mixed evenly to obtain the composition.

[0032] Example 3

[0033] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 10 parts of bifonazole, 10 parts of quercetin, 10 parts of matrine, 0.04 parts of natamycin, 50 parts of 2% iodine tincture, and 200 parts of ethanol with a volume concentration of 85%.

[0034] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, bifonazole, quercetin, matrine and ethanol with a volume concentration of 80% are ultrasonically mixed according to weight, and the ultrasonic power is set to 80W, the ultrasonic time is 0.5h, and the ultrasonic temperature is 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are mixed evenly to obtain the composition.

[0035] Example 4

[0036] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 3 parts of bifonazole, 5 parts of quercetin, 5 parts of matrine, 0.03 parts of natamycin, 40 parts of 2% iodine tincture, and 170 parts of ethanol with a volume concentration of 85%.

[0037] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, bifonazole, quercetin, matrine and ethanol with a volume concentration of 80% are ultrasonically mixed according to weight, and the ultrasonic power is set to 80W, the ultrasonic time is 0.5h, and the ultrasonic temperature is 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are mixed evenly to obtain the composition.

[0038] Comparative Example 1

[0039] The same as Example 1, except that bifonazole is not added to the formula.

[0040] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 8 parts of quercetin, 8 parts of matrine, 0.03 parts of natamycin, 40 parts of 2% iodine tincture, and 180 parts of ethanol with a volume concentration of 80%.

[0041] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, by weight, quercetin, matrine and ethanol with a volume concentration of 80% are ultrasonically mixed, the ultrasonic power is set to 80W, the ultrasonic time is set to 0.5h, and the ultrasonic temperature is set to 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are evenly mixed to obtain.

[0042] Comparative Example 2

[0043] The same as Example 1, except that quercetin and matrine are not added to the formula.

[0044] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 16 parts of bifonazole, 0.03 parts of natamycin, 40 parts of 2% iodine tincture, and 180 parts of ethanol with a volume concentration of 80%.

[0045] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, bifonazole and ethanol with a volume concentration of 80% are ultrasonically mixed according to weight, the ultrasonic power is set to 80W, the ultrasonic time is 0.5h, and the ultrasonic temperature is 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are mixed evenly to obtain the composition.

[0046] Comparative Example 3

[0047] The same as Example 1, except that quercetin is not added to the formula.

[0048] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 4 parts of bifonazole, 12 parts of matrine, 0.03 parts of natamycin, 40 parts of 2% iodine tincture, and 180 parts of ethanol with a volume concentration of 80%.

[0049] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, bifonazole, matrine and ethanol with a volume concentration of 80% are ultrasonically mixed according to weight, and the ultrasonic power is set to 80W, the ultrasonic time is 0.5h, and the ultrasonic temperature is 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are mixed evenly to obtain the composition.

[0050] Comparative Example 4

[0051] The same as Example 1, the only difference is that matrine is not added into the formula.

[0052] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 4 parts of bifonazole, 12 parts of quercetin, 0.03 parts of natamycin, 40 parts of 2% iodine tincture, and 180 parts of ethanol with a volume concentration of 80%.

[0053] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, bifonazole, quercetin and ethanol with a volume concentration of 80% are ultrasonically mixed according to weight, and the ultrasonic power is set to 80W, the ultrasonic time is 0.5h, and the ultrasonic temperature is 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are mixed evenly to obtain the composition.

[0054] Comparative Example 5

[0055] The same as Example 1, the only difference is the number of components in the formula.

[0056] An anti-infection pharmaceutical composition is composed of the following raw materials in parts by weight: 4 parts of bifonazole, 20 parts of quercetin, 20 parts of matrine, 0.01 parts of natamycin, 40 parts of 2% iodine tincture, and 300 parts of ethanol with a volume concentration of 80%.

[0057] A preparation method of a pharmaceutical composition for treating fungal infection is as follows: firstly, bifonazole, quercetin, matrine and ethanol with a volume concentration of 80% are ultrasonically mixed according to weight, and the ultrasonic power is set to 80W, the ultrasonic time is 0.5h, and the ultrasonic temperature is 50°C to obtain solution 1; then, natamycin and 2% iodine tincture are mixed at room temperature to obtain solution 2; finally, solution 1 and solution 2 are mixed evenly to obtain the composition.

[0058] Experimental Example 1 In vitro antibacterial experiment

[0059] 1. Microbial inoculation

[0060] Bacteria: Escherichia coli (CICC 10389), Staphylococcus aureus (ATCC 29970) and Streptococcus (CICCB0182); Fungi: Candida albicans (ATCC 2091).

[0061] Adjust the OD of the liquid culture medium containing bacteria 595 to 0.30-0.35 (bacterial density is 10 8 CFU / mL), diluted 100-fold with sterile saline (10 6 CFU / mL), 100 μL of each bacteria was added to LB nutrient agar medium and spread evenly, the plate was covered and dried at room temperature for 5 min; fungi were counted by hemocytometer and diluted to 10 5 CFU / mL, take 100 μL of fungi and add it to Sabouraud glucose agar medium, spread it evenly, cover the plate, and dry it at room temperature for 5 minutes.

[0062] 2. Experimental Procedure

[0063] The anti-infective pharmaceutical compositions prepared in Examples 1-4 and Comparative Examples 1-5 of the present invention were diluted 2 times with physiological saline as samples, added to the sterilized and dried filter paper, and soaked for 1 hour. The soaked filter paper was placed on the culture medium inoculated with bacteria, 20 μL of the sample was added to the Oxford cup, and it was left to stand for 30 minutes, and then placed in an incubator for constant temperature and wet culture (36°C, 24 hours for bacteria; 30°C, 24 hours for fungi), and cultured horizontally for 7 days. The plate that reached the culture time was taken out, and the diameter (mm) of the antibacterial zone was measured by the cross method. Each embodiment and comparative example corresponded to different strains, and the experiment was repeated three times. The antibacterial results are shown in Table 1.

[0064] The calculation formula of the antibacterial rate is as follows:

[0065]

[0066] The experimental results are shown in Table 1. The pharmaceutical compositions prepared in Examples 1-4 of the present invention have strong antibacterial and bactericidal effects on Escherichia coli, hemolytic Staphylococcus, Streptococcus and Candida. It can be seen from Example 1 and Comparative Examples 1-4 that the synergistic effect of bifonazole, quercetin and matrine significantly enhances the antibacterial effect (P<0.01).

[0067] Table 1 In vitro antibacterial test results

[0068]

[0069] Note: Compared with Comparative Example 1, * indicates P < 0.05, ** Indicates P<0.01.

[0070] Experimental Example 2 Clinical Experiment

[0071] A total of 180 cases of tinea corporis and cruris were divided into 9 groups according to the time of consultation, with 20 cases in each group. Medication: After local cleaning, the pharmaceutical composition solutions prepared in Examples 1-4 and Comparative Examples 1-5 were evenly applied to the affected area, once a day, and any other treatment was stopped during the treatment period. The course of treatment: 2 weeks of tinea corporis and cruris. The comprehensive efficacy evaluation results are shown in Table 2.

[0072] Clinical efficacy evaluation: There are four levels of evaluation: basic cure (basic recovery), marked effect, improvement, and ineffectiveness; among which, the percentage of improvement of symptom / sign indicators (efficacy index) a = (pre-treatment score - post-treatment score) / pre-treatment score × 100%.

[0073] Basic recovery: The improvement rate of symptoms / signs is ≥90%;

[0074] Significant effect: 60%≤a<90%;

[0075] Improvement: 20%≤a<60%;

[0076] Ineffective: a<20% or continues to worsen.

[0077] Clinical effective rate = (number of clinically effective cases + number of cured cases) / total number of cases × 100%.

[0078] The experimental results show that the efficacy of the pharmaceutical compositions prepared in Examples 1-4 of the present invention on tinea corporis and cruris is higher than that in Comparative Examples 1-5.

[0079] Among them, bifonazole, quercetin and matrine synergistically promoted the therapeutic effect of tinea corporis and cruris.

[0080] Table 2 Comprehensive efficacy evaluation results

[0081]

[0082] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. An anti-infective pharmaceutical composition, characterized in that: The invention is composed of the following components by weight: 0.1-10 parts of bifonazole, 2-10 parts of quercetin, 2-10 parts of matrine, 0.02-0.04 parts of natamycin, 30-50 parts of 2% iodine tincture and 150-200 parts of ethanol.

2. The pharmaceutical composition according to claim 1, characterized in that The invention is composed of the following components by weight: 3-6 parts of bifonazole, 5-8 parts of quercetin, 5-8 parts of matrine, 0.02-0.03 parts of natamycin, 35-45 parts of 2% iodine tincture and 170-190 parts of ethanol.

3. The pharmaceutical composition according to any one of claims 1 to 2, characterized in that The volume concentration of the ethanol is 75-85%.

4. A method for preparing the pharmaceutical composition according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: firstly, by weight, ultrasonically mixing bifonazole, quercetin, matrine and ethanol to obtain solution 1; then, mixing natamycin and 2% iodine tincture to obtain solution 2; and finally, mixing solution 1 and solution 2 to obtain.

5. An anti-infective preparation, characterized in that: The invention comprises the pharmaceutical composition according to any one of claims 1 to 3 or the pharmaceutical composition prepared by the preparation method according to claim 4.

6. The anti-infective preparation according to claim 5, characterized in that: The dosage form of the preparation is a solution.

7. Use of the pharmaceutical composition according to any one of claims 1 to 3, the pharmaceutical composition prepared by the preparation method according to claim 4, or the anti-infective preparation according to any one of claims 5 to 6 in the preparation of drugs for preventing and treating bacterial infectious diseases.

8. The use according to claim 7, characterized in that: The bacterial infectious diseases include dermatophytosis.

9. The use according to claim 8, characterized in that: The pathogens include at least one of Staphylococcus aureus, Staphylococcus haemolyticus, Escherichia coli, Streptococcus, Enterococcus faecalis and Candida; the dermatophytosis includes at least one of tinea manuum and pedis, tinea corporis and cruris, tinea unguium and tinea capitis.

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