Compound beriberi powder as well as preparation method and medical application thereof

Abstract

The invention discloses compound beriberi powder as well as a preparation method and medical application thereof, and relates to the technical field of pharmaceutical preparations. The beriberi powder is prepared from 8 parts of salicylic acid powder, 6 parts of boric acid powder, 4 parts of benzoic acid powder, 1 part of tannic acid powder, 1 part of furacilin powder and 2 parts of radix sophorae flavescentis superfine powder, the radix sophorae flavescentis superfine powder is prepared by performing CO2 supercritical extraction on radix sophorae flavescentis and then performing spray drying, the particle size is smaller than or equal to 20 micrometers, and the mass content of radix sophorae flavescentis total alkaloids is larger than or equal to 15%. According to the invention, the ultra-fine pulverization and the high-content total alkaloid are cooperated with the organic acid and the antibacterial drug, so that the multi-target effects of bacteriostasis, itching relieving, convergence and cutin exfoliation are realized; the diameter of an in-vitro inhibition zone is greater than or equal to 22mm, the cure rate of a guinea pig model reaches 98%, and the skin irritation index is less than or equal to 0.2; the preparation is simple in process, stable in quality and suitable for treating and preventing dipping erosive, blister and keratinized beriberi.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a compound beriberi powder, a preparation method thereof and medical uses thereof. Background Art

[0002] Tinea pedis (commonly known as athlete's foot) is a chronic, recurring fungal infection caused by dermatophytes invading the stratum corneum of the feet. The primary causative agents are Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum. Clinical manifestations include interdigital maceration, blisters, keratinization, desquamation, and an unpleasant odor, severely impacting patients' quality of life.

[0003] Currently, the topical preparations available on the market can be roughly divided into three categories:

[0004] Single or compound chemical antifungal powders / tinctures, such as terbinafine powder and bifonazole powder. These preparations have a clear antifungal effect in the short term, but long-term use can easily lead to drug resistance, and the recurrence rate after discontinuation of the drug can reach over 20%;

[0005] Compound preparations containing hormones or keratin peels can quickly relieve itching and remove dandruff, but they are prone to skin atrophy, pigmentation, and secondary bacterial infection.

[0006] Traditional powders or effervescent tablets mainly composed of Chinese medicinal herbs such as Sophora flavescens, Phellodendron amurense, and Cnidium monnieri are mostly made of ordinary crushed or water-decocted concentrated raw materials, with low cell wall rupture rate, low release rate of total Sophora flavescens alkaloids, slow onset of effect, long course of treatment, and poor efficacy for blister and keratotic tinea pedis.

[0007] In summary, the existing technologies generally have the following deficiencies:

[0008] a) The antibacterial spectrum is narrow, and the effect on mixed infection or polymorphic tinea pedis is limited;

[0009] b) Traditional Chinese medicines such as Sophora flavescens have low active ingredient content, large particle size, and poor bioavailability;

[0010] c) Exfoliation and anti-inflammatory and astringent effects fail to work simultaneously, resulting in a long course of treatment and a high recurrence rate;

[0011] d) Some preparations contain organic solvents or hormones, which may potentially damage the skin barrier.

[0012] Therefore, developing an external-use powder that takes into account fast-acting, broad-spectrum, low recurrence rate and good safety remains a technical problem that needs to be urgently solved in this field. Summary of the Invention

[0013] (1) Technical problems solved

[0014] In view of the deficiencies in the prior art, the present invention aims to provide a compound athlete's foot powder which has a precise efficacy, a rapid onset of action, a low recurrence rate, low irritation and is easy to industrialize and produce.

[0015] (2) Technical solution

[0016] After in vitro antibacterial and animal model screening, it was determined that the composition of the compound beriberi powder of the present invention in parts by weight is:

[0017] 8 grams of salicylic acid, 6 grams of boric acid, 4 grams of benzoic acid, 1 gram of tannic acid, 1 gram of nitrofural, and 2 grams of Sophora flavescens superfine powder; wherein the Sophora flavescens superfine powder is obtained by the following steps:

[0018] a) Sophora flavescens slices are dried at a low temperature below 60°C until the moisture content is ≤10%;

[0019] b) using CO2 as the supercritical fluid, supercritical extraction was performed under the conditions of a pressure of 25 MPa, a temperature of 45°C, and an extraction time of 2 h;

[0020] c) The extract was spray-dried at an air inlet temperature of 160° C. and an air outlet temperature of 75° C. to obtain ultrafine Sophora flavescens powder with a particle size of ≤20 μm. The total alkaloid content of Sophora flavescens was ≥15% w / w as determined by HPLC.

[0021] (3) Beneficial effects

[0022] The present invention provides a compound beriberi powder, a preparation method thereof, and medical uses thereof. It has the following beneficial effects:

[0023] 1. Strong antibacterial activity: MIC of Trichophyton rubrum and Trichophyton mentagrophytes 90 ≤0.125 mg / mL;

[0024] 2. Short treatment course and low recurrence rate: A randomized controlled clinical trial of 200 cases showed that the cure rate was 98% within 7 days and the recurrence rate was ≤4% within 6 months;

[0025] 3. Low irritation: Rabbit skin irritation index is 0.18 (reversible mild erythema);

[0026] 4. The cell wall breaking rate of Sophora flavescens ultrafine powder is ≥98%, and the bioavailability is significantly improved, which can reduce the dosage and consumption of medicinal materials;

[0027] 5. The process is simple and is operated at room temperature throughout the process, making it suitable for industrialization. DETAILED DESCRIPTION

[0028] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of them. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0029] Embodiment 1 (best embodiment)

[0030] 800 g of salicylic acid (100 mesh), 600 g of boric acid (100 mesh), 400 g of benzoic acid (100 mesh), 100 g of tannic acid (120 mesh), and 100 g of nitrofural (120 mesh) were weighed and placed in a double-cone mixer and mixed at 15 rpm at room temperature for 12 min to obtain mixture A. 200 g of ultrafine Sophora flavescens powder (D90 = 18 μm, total alkaloids 16.2%) was added to mixture A and mixing was continued for 18 min. The mixture was then packaged into 10 g / bags, sealed in aluminum foil bags with heat pressure, and sterilized by cobalt-60 irradiation.

[0031] Example 2

[0032] Take 10 g of the compound athlete's foot powder obtained in Example 1 and sprinkle it evenly between the toes and soles of the affected feet, twice a day for 7 consecutive days.

[0033] Test Example 1 In vitro antibacterial test

[0034] The MIC of the present invention against Trichophyton rubrum ATCC 4438 was determined to be 0.125 mg / mL according to CLSIM38-A2, which was significantly better than the control commercial powder of 0.5 mg / mL.

[0035] Clinical efficacy of test example 2

[0036] Two hundred patients with keratotic tinea pedis were randomly divided into a treatment group (100 cases) and a control group (100 cases each). The treatment group received the product of Example 1, while the control group received commercially available 1% terbinafine. After 7 days, 98 patients in the treatment group were cured, 2 showed marked improvement, while 84 patients in the control group were cured, 11 showed marked improvement, and 5 showed no effect. The difference was statistically significant (P < 0.01).

[0037] The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention can be implemented in other specific forms without departing from the spirit or essential characteristics of the present invention. Therefore, the embodiments should be regarded as illustrative and non-restrictive in all respects. The scope of the present invention is defined by the appended claims rather than the foregoing description, and all changes that come within the meaning and range of equivalents of the claims are intended to be included therein.

[0038] In addition, it should be understood that although this specification is described in terms of implementation methods, not every implementation method contains only one independent technical solution. This narrative method of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment can also be appropriately combined to form other implementation methods that can be understood by those skilled in the art.

Claims

1. A compound beriberi powder, characterized in that: It is composed of the following components in parts by weight: 8 parts of salicylic acid powder; 6 parts of boric acid powder; 4 parts of benzoic acid powder; 1 part tannic acid powder; 1 part of nitrofurazone powder; 2 parts of Sophora flavescens superfine powder.

2. The compound beriberi powder according to claim 1, characterized in that The ultrafine powder of Sophora flavescens is obtained by spray drying after CO2 supercritical extraction, with a particle size of ≤20 μm and a total Sophora flavescens alkaloid content of ≥15%.

3. The compound beriberi powder according to claim 1, characterized in that The particle sizes of the salicylic acid powder, boric acid powder, benzoic acid powder, tannic acid powder and nitrofural powder are all sieved through 80-120 meshes.

4. The method for preparing the compound beriberi powder according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) Weigh each component by weight; (2) salicylic acid powder, boric acid powder, benzoic acid powder, tannic acid powder, and nitrofural powder were mixed at 25°C ± 5°C and relative humidity ≤ 45% for 10 to 15 minutes to obtain a mixture A; (3) Add ultrafine powder of Sophora flavescens to mixture A and continue mixing for 15 to 20 minutes; (4) Divide and seal.

5. The preparation method according to claim 4, characterized in that The mixing equipment for steps (2) and (3) is a double-cone three-dimensional motion mixer with a rotation speed of 12 to 15 rpm.

6. Use of the compound beriberi powder according to any one of claims 1 to 3 in the preparation of an external-use medicament for treating or preventing beriberi caused by dermatophytes.

7. The use according to claim 6, characterized in that The types of athlete's foot include maceration and erosion type, blister type and keratosis type.