CN103638062B - Dashing agent of a kind of anti-dermatophytosis and preparation method thereof - Google Patents

Abstract

A pouring agent for anti-dermatophytes, characterized in that: the pouring agent is made according to the ratio of dissolving 0.56g to 5g of Galla gall extract per 100ml mixed solvent, and the 100ml mixed solvent consists of the following components : Penetration enhancer 2ml~6ml, solubilizer 0.5ml~2ml, solvent 30ml~50ml, the balance is auxiliary agent. The pouring agent prepared by the invention has uniform dispersion of main ingredients, transparent and slightly viscous liquid, convenient administration, long-lasting effect, less toxic and side effects, meets the requirements of Chinese Pharmacopoeia, and has controllable quality. Pharmacodynamic studies show that the present invention has preventive and therapeutic effects on skin mycosis caused by dermatophyte infection, and has auxiliary therapeutic effect on secondary inflammation caused by fungal infection.

Description

A kind of anti-dermatophyte pouring agent and preparation method thereof

technical field

The invention relates to an anti-dermatophyte pour-on and a preparation method thereof, in particular to a traditional Chinese medicine pour-on for preventing and treating dermatophytosis caused by dermatophyte infection and a preparation method thereof.

Background technique

Dermatophyte is one of the diseases harmful to the animal breeding industry caused by filamentous fungus invading the cuticle of the skin and its appendages. Highly contagious zoonotic contact skin disease, also known as "dermatophytosis". This disease mainly affects animal fur, and symptoms such as increased dander, scab, hair loss, exudation, folliculitis and itching appear, and severe cases can cause body malnutrition, growth retardation, and reduced feed remuneration, which directly affect the output and quality of fur. Quality, reduce the production performance of animals and the survival rate of cubs, causing serious economic losses to the breeding industry.

The treatment methods for fungal skin ringworm include general treatment, combination of traditional Chinese and western medicine, and physical therapy. In view of the wide application of broad-spectrum antibacterial drugs, immunosuppressants, and chemoradiotherapy drugs, the drug resistance of fungi is becoming stronger and stronger. Therefore, the most effective method among the above-mentioned treatment methods is the combination of Chinese and Western medicine. In this case, it is an inevitable trend to develop antifungal natural products with less toxic side effects, less drug resistance, and less environmental impact. It is necessary to find and use natural antifungal active ingredients in medicinal plants as the parent to design new antifungal drugs. Become a new hotspot of research and development. Single or compound traditional Chinese medicine has obvious curative effect and good antibacterial effect for external use, and has obvious curative effect in the treatment of fungal infection and mixed infection.

Gallnut is the gall on the leaves of the Anacardiaceae plant Saltella , Populus chinensis or Populus red bran, which is mainly formed by the gallnut aphid ( Melaphischinensis (Bell)Baker). Its main active ingredient, tannic acid, is a water-soluble polyphenolic compound with multiple activities of antioxidant, antibacterial, antiviral, and antitumor. Gallnut is often used to treat skin ringworm together with other various traditional Chinese medicines, and its compound process is complicated and the cost is high.

Contents of the invention

The purpose of the present invention is to provide a kind of anti-dermatophytes that has significant killing effect on dermatophytes, less toxic and side effects, low cost and simple process in view of the toxic and side effects of the existing antifungal western medicines and the high price and the complexity of the compound process. A pouring agent for skin mycosis caused by ringworm infection and a preparation method thereof.

The present invention adopts the extract of the Chinese medicine Galla chinensis, and strives to develop an external pouring agent for treating skin mycosis caused by dermatophyte infection with remarkable curative effect, low toxic and side effects, low cost and simple process.

The object of the present invention is implemented through the following technical solutions: a kind of anti-dermatophyte pouring agent, with single Chinese medicine extract as the main agent, under the effect of auxiliary agents such as transdermal accelerators, it is evenly dispersed in A slightly viscous off-white liquid preparation of single traditional Chinese medicine is formed in the matrix. Specifically:

A kind of anti-dermatophyte pour-on agent, this pour-on agent is made according to the ratio of the Galla gall extract of 0.56g～5g per 100ml mixed solvent is dissolved, and described 100ml mixed solvent is made up of the following components:

Transdermal accelerator 2ml～6ml

Solubilizer 0.5ml～2ml

Solvent 30ml～50ml

Auxiliary balance.

The Galla galla extract is prepared by the following preparation method: Take Galla galla powder and pass it through a 20-mesh sieve to obtain a coarse powder, use 20 times the amount of 50% ethanol to ultrasonically extract at 60°C for 30 minutes, filter and concentrate the filtrate to a paste , and put it in an oven at 55°C until it is dried to a constant weight to obtain Galla gall extract.

The skin penetration enhancer is one or more of azone, 0.5% borneol ethanol solution, and 1% sodium dodecylsulfonate aqueous solution.

The solubilizer is Tween-80 and/or Span.

The solvent is 1,2-propanediol.

The auxiliary agent is 60-100% ethanol.

In the present invention:

1) The ratio of transdermal enhancer, solubilizer, solvent and main drug is optimized by orthogonal test method, which is comprehensive and easy to operate.

2) The auxiliary agent ethanol makes up the remaining volume to reach the concentration level for the drug to exert its curative effect.

3) Dilute each level of pouring agent according to a certain dilution method, measure its absorbance under a certain wavelength condition, and determine the best ratio method of Galla gall pouring agent.

The pouring agent of the present invention is safe to humans, animals and the environment. The pouring agent of the present invention is a liquid preparation, which is characterized by off-white, slightly viscous liquid; the preparation process is simple, the administration is convenient, and the long-lasting effect; when used, it is diluted by a certain multiple and then poured on the body. , The drug enters the body through the skin and reaches the target organ to exert its curative effect.

Since external medicines for the treatment of dermatophytosis usually have very little transdermal penetration, we make them into a liquid preparation containing a transdermal enhancer, which is convenient for administration and has a long-lasting effect, so as to facilitate more penetration of the drug into the skin. Comes into contact with the fungus to function. The solvent 1,2-propanediol has a synergistic promoting effect on azone, and its addition can promote the penetration of the drug into the skin, so that it avoids the shortcoming of low drug utilization rate of general external preparations, and better exerts the therapeutic effect. Therefore, the pouring agent of the present invention has good permeability and high absorption rate, which is beneficial for medicines to enter the skin and improves the efficacy of medicines.

The pouring agent prepared by the invention has uniform dispersion of main ingredients, transparent and slightly viscous liquid, convenient administration, long-lasting effect, less toxic and side effects, meets the requirements of Chinese Pharmacopoeia, and has controllable quality.

Pharmacodynamic studies show that the present invention has preventive and therapeutic effects on skin mycosis caused by dermatophyte infection, and has auxiliary therapeutic effect on secondary inflammation caused by fungal infection.

detailed description

The present invention is further described by specific examples below, but the examples are only for illustration and cannot limit the scope of the present invention.

Example 1

Take 0.56g gallic gall extract and dissolve it in 30ml of 1,2-propanediol, then add 2ml of azone, 1ml of Tween-80, 67ml of 90% ethanol in succession, and mix well; then divide the finished product Sealed in vials, about 5~20ml per bottle. After testing, the properties of this pouring agent are off-white, transparent and slightly viscous liquid, and the pH, loading capacity and microbial limit are all qualified.

Example 2

Dissolve 1.67g of Galla Chinese medicinal extract in 40ml of 1,2-propanediol, then add 4ml of azone, 0.5ml of Tween-80, 55.5ml of 90% ethanol in succession, and mix well; then the finished product Packed in vials and sealed, about 5~20ml per bottle. After testing, the properties of this pouring agent are off-white, transparent and slightly viscous liquid, and the pH, loading capacity and microbial limit are all qualified.

Example 3

Take 5g of Galla Chinese medicinal extract and dissolve it in 50ml of 1,2-propylene glycol, then add 6ml of azone, 2ml of Tween-80, and 42ml of 90% ethanol in succession, and mix well; then distribute the finished product in Sealed in vials, about 5~20ml per bottle. After testing, the properties of this pouring agent are off-white, transparent and slightly viscous liquid, and the pH, loading capacity and microbial limit are all qualified.

1, the pouring agent that embodiment 1-embodiment 3 makes has carried out following anti-dermatophyte drug efficacy test:

The test temperature was 20°C, repeated 3 times, and the concentration of 100% pouring agent was used to act on Candida albicans, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypsum for 20 minutes. The killing effect is shown in Table 1.

Table 1 The killing effect of the pouring agents prepared in Examples 1-3 on Candida albicans, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypsumoides.

2. The MIC and MFC values of the Galla gall extract pouring agent made in Example 2 to Candida albicans, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypsum-like four fungi are:

The MIC and MFC values against Candida albicans are 0.0125mg/ml and 0.05mg/ml respectively;

The MIC and MFC values for Trichophyton mentagrophytes are 0.025mg/ml and 0.05mg/ml respectively;

The MIC and MFC values against Microsporum canis are 0.025mg/ml and 0.025mg/ml respectively;

The MIC and MFC values against Microsporum gypsumoides are 0.025mg/ml and 0.05mg/ml, respectively.

3. Observation of clinical symptoms

Select 50 rabbits infected with dermatophytes, and randomly divide them into 5 groups (group I blank control group, group II dacryline cream treatment control group, group III example 1 treatment group, group IV example 2 treatment group, group V example 3 treatment groups), 10 rats in each group; method of use: clean the affected area, then take an appropriate amount of therapeutic agent and apply it to the skin of the affected area, 2 times/day, use continuously for 14 days to observe the curative effect and count the effective rate; 1-5 days after stopping the drug The cure rate was counted, and the recurrence rate was counted 10-15 days after drug withdrawal. Before the medication, the rabbits infected with dermatophytes had skin lesions on the back, ears, limbs, etc., with erythema and severe hair loss; after 14 days of medication, the curative effects of each group were as follows:

Group Ⅰ blank control group: erythema and severe hair loss still existed in the skin lesions, and a small amount of dander appeared in some cases; the symptoms of dermatophyte infection did not improve.

Group II Daknine cream treatment control group: after 14 days of treatment, the erythema and hair loss in the skin lesions disappeared, and new hair grew. 1-5 days after drug withdrawal, 90% were cured, and 10-15 days after drug withdrawal, the recurrence rate was 10%.

Group III Example 1 Treatment group: after 14 days of medication, erythema and hair loss in the skin lesions basically disappeared, and occasionally new hairs grew out of the affected area, no adverse reactions occurred, and the effective rate was 70%; statistics were collected 1-5 days after stopping the drug 60% were cured, and the statistical recurrence rate was 30% in 10-15 days after drug withdrawal.

Group IV, Example 2 Treatment group: after 14 days of medication, erythema and depilation at the skin lesion disappeared, new hairs grew out of the affected area, no adverse reactions occurred, and the effective rate was 90%; 90% were cured 1-5 days after drug withdrawal %, the statistical recurrence rate was 10% 10-15 days after drug withdrawal.

Group V and Example 3 Treatment group: after 14 days of medication, erythema and depilation at the skin lesion disappeared, new hairs grew out of the affected area, no adverse reactions occurred, and the effective rate was 90%; 90% were cured 1-5 days after drug withdrawal %, the statistical recurrence rate was 10% 10-15 days after drug withdrawal.

It can be seen that, compared with the blank control group, the pour-on formulations of embodiment 2 and embodiment 3 all have a good curative effect, and the pour-on formulation of embodiment 1 has a certain curative effect; Example 3 pouring agent has played the same therapeutic effect, and can be used for clinical treatment of rabbit fungal dermatophytosis.

Claims (1)

1. A pour-on agent for anti-dermatophytes, characterized in that: the pour-on agent is made in a ratio of dissolving 0.56g～5g of Galla gall extract in every 100ml mixed solvent, and the 100ml mixed solvent is composed of the following amounts: grouped into: Transdermal accelerator 2ml～6ml Solubilizer 0.5ml～2ml 1,2-Propanediol 30ml～50ml 60%-100% ethanol balance; The Galla galla extract is prepared by the following preparation method: Take Galla galla powder and pass it through a 20-mesh sieve to obtain a coarse powder, use 20 times the amount of 50% ethanol to ultrasonically extract at 60°C for 30 minutes, filter and concentrate the filtrate to a paste , and put it in an oven at 55°C until it is dried to a constant weight to obtain Galla gall extract; Described transdermal accelerator is azone, 0.5% borneol ethanol solution, one or more in 1% sodium dodecylsulfonate aqueous solution; The solubilizer is Tween-80 and/or Span.