Special compound Chinese herbal medicine ointment for treating onychomycosis and preparation method thereof

Abstract

The invention belongs to the technical field of Chinese herbal medicine preparations, and particularly relates to composite Chinese herbal medicine paste special for treating onychomycosis and a preparation method thereof. The composition comprises an active component and a matrix component, wherein the active component comprises the following components: cortex phellodendri, coptis chinensis, radix sophorae flavescentis, cortex dictamni, fructus kochiae, liquorice, fructus cnidii, rheum officinale, indigo naturalis, pseudo-ginseng powder, sesame oil, peppermint essential oil and folium eucalypti essential oil; the matrix component is prepared from the following components: chitosan, disodium glycerophosphate, hydroxypropyl methyl cellulose, potassium sorbate, citric acid, sodium citrate, an emulsifier, a humectant and an antioxidant. Various traditional Chinese medicines are used for synergistically inhibiting onychomycosis pathogenic fungi; cnidium monnieri and rheum officinale construct a multi-layer antibacterial and anti-inflammatory system, indigo naturalis and pseudo-ginseng promote blood circulation and tissue repair, mint and folium eucalypti essential oil improve the transdermal absorption rate, a chitosan-glycerophosphate system is in contact with body temperature to form a gel layer, and the drug residence time is prolonged.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese herbal medicine preparations, and particularly relates to a composite Chinese herbal medicine ointment for treating onychomycosis and a preparation method thereof. Background Art

[0002] Onychomycosis is a chronic disease of the nail plate or its surrounding tissues caused by fungal infection, mainly affecting fingernails and toenails. It is not only a cosmetic problem, but may also cause pain and other complications, such as paronychia and nail bed separation, which have a negative impact on the patient's quality of life. The disease is usually caused by dermatophytes, yeasts, or other non-dermatophyte fungi, the most common of which is Trichophyton rubrum. With the development of socioeconomic development and changes in personal hygiene habits, the incidence of onychomycosis has gradually increased worldwide, especially among people working or living in humid environments. It is estimated that about 2%-18% of the world's population is affected by onychomycosis, and this proportion is higher in the elderly. Humid environments, use of public bathrooms, and impaired immune systems are all risk factors for infection. Due to its high recurrence rate, the treatment of onychomycosis has become a long-term concern in the medical community. At present, the methods for treating onychomycosis mainly include topical medication, oral antifungal drugs and physical therapy. Although topical medication can reduce systemic side effects, it often requires long-term application and has limited effect on deep fungal infections; oral antifungal drugs have relatively good efficacy, but may cause serious side effects such as liver and kidney damage, and are not suitable for all patients. In traditional Chinese medicine, onychomycosis is regarded as caused by damp-heat evil spirits, and the treatment principle is to clear away heat and detoxify, dry dampness and stop itching. Many Chinese herbal medicines contain natural antibacterial ingredients that can inhibit fungal growth, while promoting blood circulation and metabolism, which helps to accelerate the recovery of nails to a healthy state. For example, medicinal materials such as Phellodendron chinense, Sophora flavescens, and Sanguisorba officinalis have been shown to have a good inhibitory effect on fungi; while Angelica sinensis and Chuanxiong can improve local blood supply and help repair damaged tissues. Based on the above problems, an efficient, safe and easy-to-use onychomycosis compound Chinese herbal ointment was developed. Summary of the invention

[0003] In view of the defects of the prior art, the object of the present invention is to provide a composite Chinese herbal ointment for treating onychomycosis and a preparation method thereof.

[0004] The technical effect of the present invention is achieved by the following technical scheme: a composite Chinese herbal ointment for treating onychomycosis, which comprises an active ingredient and a matrix component, wherein the active ingredient comprises the following components in parts by weight: 10 to 20 parts of Phellodendron amurense, 10 to 20 parts of Coptis chinensis, 5 to 10 parts of Sophora flavescens, 5 to 8 parts of Dictamni cortex, 5 to 10 parts of Kochia scoparia, 5 to 8 parts of Licorice, 5 to 10 parts of Cnidium monnieri, 5 to 10 parts of Rhubarb, 3 to 5 parts of Indigo naturalis, and 3 to 5 parts of Tripterygium wilfordii. Seven powder, 20-30 parts of sesame oil, 1-2 parts of peppermint essential oil, 1-1.5 parts of eucalyptus essential oil; the matrix component comprises the following components in parts by weight: 8-12 parts of chitosan, 4-8 parts of disodium glycerophosphate, 2-3 parts of hydroxypropyl methylcellulose, 0.3-0.5 parts of potassium sorbate, 1-1.5 parts of citric acid, 1.5-2 parts of sodium citrate, 1-2 parts of emulsifier, 1-3 parts of moisturizer and 0.3-0.5 parts of antioxidant.

[0005] Preferably, the emulsifier is any one of lecithin, Tween-80 and Span-80.

[0006] Preferably, the moisturizing agent is any one of glycerin, propylene glycol and hyaluronic acid.

[0007] Preferably, the antioxidant is any one of vitamin E, tea polyphenols, butylated hydroxyanisole and propyl gallate.

[0008] Preferably, another aspect of the present invention is to provide a method for preparing a composite Chinese herbal ointment for treating onychomycosis, and the specific preparation steps are as follows: S1: clean and dry Phellodendron chinense, Coptis chinensis, Sophora flavescens, Dictamni cortex, Kochia scoparia, Licorice root, Cnidium monnieri, Rhubarb, Indigo naturalis and Panax notoginseng powder, add them into 5wt% acetic acid solution, stir and mix thoroughly, soak at room temperature for 24h, stir every 6h, filter, centrifuge, filter and obtain acetic acid extract; S2: adding the acetic acid extract prepared in step S1 into a vacuum concentration device, setting the temperature to 40-50° C., stirring at 100-300 rpm, and concentrating for 2-4 hours under vacuum to obtain a Chinese medicine concentrate; S3: adding citric acid and sodium citrate into deionized water, stirring and dissolving them uniformly, and obtaining a citric acid-sodium citrate buffer solution; slowly dropping the citric acid-sodium citrate buffer solution into the concentrated Chinese medicine solution prepared in step S2, stirring and mixing them uniformly, and obtaining a mixed solution; S4: adding chitosan to a 5wt% acetic acid solution, stirring and dissolving uniformly to obtain a chitosan solution; adding disodium glycerophosphate to the chitosan solution, stirring and dispersing uniformly to obtain a chitosan-glycerophosphate system; adding hydroxypropyl methylcellulose to deionized water, heating to 50-60°C, stirring and dissolving uniformly to obtain a 1-2wt% hydroxypropyl methylcellulose solution; S5: slowly adding the mixed solution prepared in step S3 to the chitosan-glycerophosphate system prepared in step S4, stirring and mixing evenly, then adding the hydroxypropyl methylcellulose solution prepared in step S4, stirring and mixing, and then slowly adding the emulsifier, stirring continuously at 300-500 rpm for 1-2 hours to obtain an emulsified matrix; S6: Slowly add sesame oil, peppermint essential oil and eucalyptus essential oil to the emulsified base prepared in step S5, stir and mix evenly, then add potassium sorbate, moisturizer and antioxidant in sequence, continue stirring and disperse evenly, and then homogenize to obtain a composite Chinese herbal ointment; Preferably, in step S1, the amount of the acetic acid solution is 10 to 20 times the total weight of the substrate Chinese medicine; Preferably, in step S3, the amount of deionized water used is 5 to 8 times the total weight of citric acid and sodium citrate; Preferably, in step S4, the amount of the acetic acid solution is 30 to 50 times the weight of the substrate chitosan; Preferably, in step S6, the specific parameters of the homogenization treatment are: rotation speed 5000-6000 rpm, temperature 40-50° C., time 3-5 min, and the treatment is repeated 3 times.

[0009] The beneficial effects are as follows: The present invention adopts Phellodendron chinense and Coptis chinensis as core medicinal materials. Both are rich in berberine and other alkaloids, and have broad-spectrum antibacterial and antifungal effects. The combination of Phellodendron chinense and Coptis chinensis enhances the effects of clearing away heat and dampness, clearing away heat and detoxifying, effectively inhibiting the growth of pathogenic fungi (such as dermatophytes) of onychomycosis, and slowing down the deformation, thickening and discoloration of nails. Matrine in Sophora flavescens further enhances the antibacterial, antifungal and anti-inflammatory effects, while Dictamni can relieve itching and skin inflammation caused by fungal infection. These four medicinal materials work synergistically to form an efficient antifungal composition, which comprehensively inhibits the reproduction of pathogenic fungi. As a traditional Chinese medicine for treating skin fungal infections, Cnidium monnieri has obvious insecticidal, antipruritic and antibacterial effects, and constructs a multi-level, complementary antibacterial and anti-inflammatory system with Rhubarb; Rhubarb not only has the effects of clearing away heat and detoxifying, antibacterial and antifungal, but also promotes local blood circulation by promoting blood circulation and removing blood stasis. Indigo naturalis further plays the role of clearing away heat and detoxifying and detumescence, relieves the inflammation and swelling of the tissues around the nails, and enhances the overall anti-inflammatory and analgesic effect. Panax notoginseng mainly improves the nutrition supply and poor circulation of the nail bed in the affected area of ​​onychomycosis by promoting blood circulation and removing blood stasis and promoting microcirculation, and promotes the growth of new nails and tissue repair. As a matrix oil, sesame oil can not only dissolve and disperse the fat-soluble components in the medicinal materials, but also improve the ductility and permeability of the ointment. By adding citric acid and sodium citrate to form a stable citric acid-sodium citrate buffer system, it is effectively compatible with the chitosan-glycerophosphate system. When used, the local pH is adjusted to acidic, which not only helps the stability and activity of the effective ingredients of traditional Chinese medicine, but also enhances its solubility and permeability, ensuring the continuous and efficient effect of the drug in the affected area; in addition, using low-proportion concentrations of peppermint and eucalyptus essential oils as transdermal enhancers can enhance the penetration of drugs through the nail surface and surrounding skin, while improving the comfort of use, reducing local discomfort, and avoiding the excessive concentration of the essential oil itself, which may cause skin irritation, allergies or burning sensations, especially when the skin in the affected area has been inflamed or damaged. The addition of a low proportion of essential oils can moderately destroy the tight structure of the stratum corneum and increase the transdermal absorption rate of drug ingredients without excessively weakening the skin barrier function, thereby maintaining a state of gentle penetration and ensuring continuous and balanced release of drugs.

[0010] The present invention utilizes acetic acid to soak Chinese medicinal materials in the process. The acidic environment of acetic acid effectively destroys the cell structure of Chinese medicinal materials, promotes the dissolution of effective ingredients such as alkaloids, flavonoids and glycosides, and through its own antibacterial and antifungal capabilities, it is superimposed with Chinese medicinal ingredients to enhance the overall antifungal effect. Subsequently, low-temperature vacuum concentration technology is used to avoid thermal degradation of effective ingredients at high temperatures, maintain the integrity of active ingredients of Chinese medicine, remove moisture at the same time, retain water-soluble and alcohol-soluble effective ingredients, and reduce impurities and degradation products. Then, the extracted and concentrated Chinese medicinal ingredients are combined with a chitosan-glycerophosphate system, which is in a low-viscosity flow state at room temperature, which is convenient for preparation and application; after being applied to nails and skin, a dense gel layer is quickly formed when in contact with body temperature. Chitosan molecules are positively charged and interact with the negatively charged parts of bacterial or fungal cell walls, destroying the integrity of their cell membranes, causing leakage of cell contents, thereby achieving antibacterial and antifungal effects. At the same time, the good adhesion of chitosan and the transdermal promotion effect of peppermint and eucalyptus essential oils significantly improve the penetration efficiency of drugs through the stratum corneum. The formation of gel prolongs the retention time of drugs in the affected area, ensuring the continuous and efficient effect of the effective ingredients of traditional Chinese medicine and reducing the erosion and oxidation of drugs by the external environment. The entire ointment forms a stable drug film at body temperature to prevent the loss of drugs due to friction or washing. At the same time, the cool feeling of essential oils improves the comfort of users.

[0011] In summary, the present invention achieves the effects of comprehensively inhibiting fungal growth, reducing inflammation, etc. through the synergistic effect of multiple Chinese medicinal materials combined with chitosan gel matrix, and significantly improves the effect of treating onychomycosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings in the following description are only for the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0013] Figure 1 It is a graph showing the results of the permeation release test of the composite Chinese herbal ointment prepared in Example 2 of the present invention and Comparative Examples 2 and 3; Figure 2 It is a graph showing the stability test results of the composite Chinese herbal ointment prepared in Example 2 of the present invention and Comparative Examples 3 and 4. DETAILED DESCRIPTION

[0014] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. It should be noted that, unless otherwise specified, the raw materials involved in the present invention are purchased through conventional commercial channels.

[0015] Embodiment 1: A composite Chinese herbal ointment for treating onychomycosis, comprising active ingredients and matrix components, wherein the active ingredients comprise the following components in parts by weight: 10 parts of Phellodendron amurense, 10 parts of Coptis chinensis, parts of Sophora flavescens, 5 parts of Dictamni cortex, 5 parts of Kochia scoparia, 5 parts of Licorice, 5 parts of Cnidium monnieri, 5 parts of Rhubarb, 3 parts of Indigo naturalis, 3 parts of Panax notoginseng powder, 20 parts of sesame oil, 1 part of peppermint essential oil, and 1 part of eucalyptus essential oil; the matrix components comprise the following components in parts by weight: 8 parts of chitosan, 4 parts of disodium glycerophosphate, 2 parts of hydroxypropyl methylcellulose, 0.3 parts of potassium sorbate, 1 part of citric acid, 1.5 parts of sodium citrate, 1 part of emulsifier, 1 part of moisturizer and 0.3 part of antioxidant.

[0016] The specific preparation steps of the compound Chinese herbal ointment for treating onychomycosis are as follows: S1: clean and dry Phellodendron chinense, Coptis chinensis, Sophora flavescens, Dictamni cortex, Kochia scoparia, Licorice, Cnidium monnieri, Rhubarb, Indigo naturalis and Panax notoginseng powder, add them into 10 times of the total weight of 5wt% acetic acid solution, stir and mix thoroughly, soak at room temperature for 24h, stir every 6h, filter, centrifuge, filter, and obtain acetic acid extract; S2: adding the acetic acid extract prepared in step S1 into a vacuum concentration device, setting the temperature to 40°C, stirring at 100 rpm, and concentrating for 2 hours under vacuum to obtain a Chinese medicine concentrate; S3: adding citric acid and sodium citrate to deionized water in an amount of 5 times the total weight, stirring and dissolving them uniformly to obtain a citric acid-sodium citrate buffer solution; slowly dropping the citric acid-sodium citrate buffer solution into the concentrated Chinese medicine solution prepared in step S2, stirring and mixing them uniformly to obtain a mixed solution; S4: adding chitosan to 30 times the weight of a 5wt% acetic acid solution, stirring and dissolving uniformly to obtain a chitosan solution; adding disodium glycerophosphate to the chitosan solution, stirring and dispersing uniformly to obtain a chitosan-glycerophosphate system; adding hydroxypropyl methylcellulose to deionized water, heating to 50° C., stirring and dissolving uniformly to obtain a 1wt% hydroxypropyl methylcellulose solution; S5: slowly adding the mixed solution prepared in step S3 to the chitosan-glycerophosphate system prepared in step S4, stirring and mixing evenly, then adding the hydroxypropyl methylcellulose solution prepared in step S4, stirring and mixing, and then slowly adding lecithin, stirring at 300 rpm for 1 hour, to obtain an emulsified matrix; S6: Slowly add sesame oil, peppermint essential oil and eucalyptus essential oil to the emulsified base prepared in step S5, stir and mix evenly, then add potassium sorbate, glycerin and vitamin E in sequence, continue stirring to disperse evenly, and then homogenize, set the parameters to a speed of 5000 rpm, a temperature of 40°C, and a time of 3 min, repeat the process 3 times to obtain a composite Chinese herbal ointment.

[0017] Embodiment 2: A composite Chinese herbal ointment for treating onychomycosis, comprising active ingredients and matrix ingredients, wherein the active ingredients comprise the following components in parts by weight: 18 parts of Phellodendron amurense, 15 parts of Coptidis chinensis, 8 parts of Sophora flavescens, 6 parts of Dictamni cortex, 8 parts of Kochia scoparia, 7 parts of Licorice, 8 parts of Cnidium monnieri, 8 parts of Rhubarb, 4 parts of Indigo naturalis, 4 parts of Notoginseng powder, 25 parts of sesame oil, 1.5 parts of peppermint essential oil, and 1.2 parts of eucalyptus essential oil; the matrix ingredients comprise the following components in parts by weight: 10 parts of chitosan, 5 parts of disodium glycerophosphate, 2.5 parts of hydroxypropyl methylcellulose, 0.4 parts of potassium sorbate, 1.4 parts of citric acid, 1.8 parts of sodium citrate, 1.5 parts of emulsifier, 2 parts of moisturizer and 0.4 parts of antioxidant.

[0018] The specific preparation steps of the compound Chinese herbal ointment for treating onychomycosis are as follows: S1: clean and dry Phellodendron chinense, Coptis chinensis, Sophora flavescens, Dictamni cortex, Kochia scoparia, Licorice root, Cnidium monnieri, Rhubarb, Indigo naturalis and Panax notoginseng powder, then add into 15 times of the total weight of 5wt% acetic acid solution, stir and mix thoroughly, soak at room temperature for 24h, stir every 6h, filter, centrifuge, filter, and obtain acetic acid extract; S2: Add the acetic acid extract prepared in step S1 into a vacuum concentration device, set the temperature to 45°C, stir at 250 rpm, and concentrate for 3 hours under vacuum to obtain a Chinese medicine concentrate; S3: adding citric acid and sodium citrate to 6 times the total weight of deionized water, stirring and dissolving them uniformly to obtain a citric acid-sodium citrate buffer solution; slowly dropping the citric acid-sodium citrate buffer solution into the concentrated Chinese medicine solution prepared in step S2, stirring and mixing them uniformly to obtain a mixed solution; S4: adding chitosan to 40 times the weight of a 5wt% acetic acid solution, stirring and dissolving uniformly to obtain a chitosan solution; adding disodium glycerophosphate to the chitosan solution, stirring and dispersing uniformly to obtain a chitosan-glycerophosphate system; adding hydroxypropyl methylcellulose to deionized water, heating to 55°C, stirring and dissolving uniformly to obtain a 1.5wt% hydroxypropyl methylcellulose solution; S5: slowly adding the mixed solution prepared in step S3 to the chitosan-glycerophosphate system prepared in step S4, stirring and mixing evenly, then adding the hydroxypropyl methylcellulose solution prepared in step S4, stirring and mixing, and then slowly adding Tween-80, stirring at 500 rpm for 1.5 hours to obtain an emulsified matrix; S6: Slowly add sesame oil, peppermint essential oil and eucalyptus essential oil to the emulsified base prepared in step S5, stir and mix evenly, then add potassium sorbate, propylene glycol and tea polyphenols in sequence, continue stirring to disperse evenly, and then homogenize, set the parameters to a speed of 5500 rpm, a temperature of 45°C, and a time of 4 min, repeat the process 3 times to obtain a composite Chinese herbal ointment.

[0019] Embodiment 3: A composite Chinese herbal ointment for treating onychomycosis, comprising active ingredients and matrix ingredients, wherein the active ingredients comprise the following components in parts by weight: 20 parts of Phellodendron amurense, 20 parts of Coptis chinensis, 10 parts of Sophora flavescens, 8 parts of Dictamni cortex, 10 parts of Kochia scoparia, 8 parts of Licorice, 10 parts of Cnidium monnieri, 10 parts of Rhubarb, 5 parts of Indigo naturalis, 5 parts of Panax notoginseng powder, 30 parts of sesame oil, 2 parts of peppermint essential oil, and 1.5 parts of eucalyptus essential oil; the matrix ingredients comprise the following components in parts by weight: 12 parts of chitosan, 8 parts of disodium glycerophosphate, 3 parts of hydroxypropyl methylcellulose, 0.5 parts of potassium sorbate, 1.5 parts of citric acid, 2 parts of sodium citrate, 2 parts of emulsifier, 3 parts of moisturizer and 0.5 part of antioxidant.

[0020] The specific preparation steps of the compound Chinese herbal ointment for treating onychomycosis are as follows: S1: clean and dry Phellodendron chinense, Coptis chinensis, Sophora flavescens, Dictamni cortex, Kochia scoparia, Licorice, Cnidium monnieri, Rhubarb, Indigo naturalis and Panax notoginseng powder, add them into 5wt% acetic acid solution with 20 times the total weight, stir and mix thoroughly, soak at room temperature for 24h, stir every 6h, filter, centrifuge, filter, and obtain acetic acid extract; S2: adding the acetic acid extract prepared in step S1 into a vacuum concentration device, setting the temperature to 50°C, stirring at 300 rpm, and concentrating for 4 hours under vacuum to obtain a Chinese medicine concentrate; S3: adding citric acid and sodium citrate to deionized water in an amount of 5 to 8 times the total weight, stirring and dissolving them uniformly to obtain a citric acid-sodium citrate buffer solution; slowly dropping the citric acid-sodium citrate buffer solution into the concentrated Chinese medicine solution prepared in step S2, stirring and mixing them uniformly to obtain a mixed solution; S4: adding chitosan to 50 times the weight of a 5wt% acetic acid solution, stirring and dissolving uniformly to obtain a chitosan solution; adding disodium glycerophosphate to the chitosan solution, stirring and dispersing uniformly to obtain a chitosan-glycerophosphate system; adding hydroxypropyl methylcellulose to deionized water, heating to 60°C, stirring and dissolving uniformly to obtain a 2wt% hydroxypropyl methylcellulose solution; S5: slowly adding the mixed solution prepared in step S3 to the chitosan-glycerophosphate system prepared in step S4, stirring and mixing evenly, then adding the hydroxypropyl methylcellulose solution prepared in step S4, stirring and mixing, and then slowly adding Span-80, stirring at 400 rpm for 2 hours to obtain an emulsified matrix; S6: Slowly add sesame oil, peppermint essential oil and eucalyptus essential oil to the emulsified base prepared in step S5, stir and mix evenly, then add potassium sorbate, hyaluronic acid and butylated hydroxyanisole in sequence, continue to stir and disperse evenly, and then homogenize, set the parameters to a speed of 6000 rpm, a temperature of 50°C, and a time of 5 min, repeat the process 3 times to obtain a composite Chinese herbal ointment.

[0021] Comparative Example 1: The operation of Comparative Example 1 is basically the same as that of Example 2, except that the active ingredients in Comparative Example 1 only contain Phellodendron chinense and Coptis chinensis ointment, and other active Chinese medicinal ingredients are not contained.

[0022] Comparative Example 2: The operation of Comparative Example 2 is substantially the same as that of Example 2, except that the active ingredient in Comparative Example 2 does not contain peppermint essential oil and eucalyptus essential oil.

[0023] Comparative Example 3: The operation of Comparative Example 3 is basically the same as that of Example 2, except that no chitosan-glycerophosphate system is added in Comparative Example 3, that is, the mixed solution prepared in step S3 is directly mixed with the material in step S6 for homogenization.

[0024] Comparative Example 4: The operation of Comparative Example 4 is substantially the same as that of Example 2, except that no citric acid-sodium citrate buffer solution is added in Comparative Example 4.

[0025] Performance Test: Antifungal effect test: SDA medium was used to inoculate and culture Trichophyton rubrum and Candida albicans (10 8 / mL), and then added the composite Chinese herbal ointment (radius 5mm) prepared in Examples 1 to 3 and Comparative Examples 1 to 4 to the culture medium, and cultured at a constant temperature of 30°C for 72h. After the culture was completed, the culture dish was taken out and the size of the inhibition zone was measured. The results are shown in Table 1 below.

[0026] Table 1. Antifungal test results of compound Chinese herbal ointment

[0027] It can be seen from the results in Table 1 that the composite Chinese herbal ointment prepared by the present invention has excellent inhibitory performance against fungal microorganisms and can effectively inhibit fungal infections. Among them, the composite Chinese herbal ointment prepared with the ratio of Example 2 shows the best effect; it can be seen from the results of Comparative Example 1 and Example 2 that Comparative Example 1 only contains the core antifungal ingredients Phellodendron and Coptis chinensis, lacks the synergistic enhancement of multiple active ingredients of traditional Chinese medicine, and the antibacterial effect is significantly affected; it can be seen from the results of Comparative Example 2 and Example 2 that the lack of permeability enhancement of essential oils affects the antibacterial effect to a certain extent; it can be seen from the results of Comparative Example 3 and Example 2 that the chitosan-glycerophosphate system plays a role in stabilizing drug release in the matrix. The lack of this system makes it difficult to effectively and evenly release and distribute the drug, resulting in aggregation and stratification, which significantly reduces the antibacterial effect; it can be seen from the results of Comparative Example 4 and Example 2 that the lack of pH regulation by the buffer system affects the synergy with each active ingredient, thereby affecting the antibacterial property to a certain extent.

[0028] Transdermal absorption test: A pig skin of 5 cm × 5 cm size was used as a skin model, and the receiving medium was 50 mL of a phosphate buffer solution with a pH of 5.5. The composite Chinese herbal ointment samples (0.5 g) prepared in Example 2 of the present invention and Comparative Examples 2 and 3 were respectively applied on the skin model (1 cm × 1 cm). The transdermal diffusion cell was started, and the temperature was maintained at 37°C. 1 mL of samples were taken for testing at 0.5 h, 1 h, 2 h, 4 h, 8 h and 12 h. The drug permeability was calculated as the amount of drug permeated into the receptor fluid / (skin exposure area × time interval). The results are as follows: Figure 1 shown.

[0029] Depend on Figure 1 The results show that the composite Chinese herbal ointment prepared by the present invention has excellent permeability, can effectively and continuously penetrate the active ingredients into the skin, and can effectively avoid adverse reactions caused by excessive concentrations; from the results of Comparative Example 2 and Example 2, it can be seen that the permeation mechanism of essential oils is lacking and the permeability is affected to a certain extent; from the results of Comparative Example 3 and Example 3, it can be seen that the stability of the gel matrix is ​​lacking, the drug release is unstable, and the permeability is significantly reduced.

[0030] Stability test: The composite Chinese herbal ointment prepared in Example 2 of the present invention and Comparative Examples 3 and 4 was sealed in commercial packaging and placed at a temperature of 40°C and a relative humidity of 75% for 6 months. Samples were taken once in the first, second, third and sixth months of the test period to test the pH value and record the appearance changes. The pH change results are as follows: Figure 2 The appearance change results are shown in Table 2 below.

[0031] Table 2. Results of the stability test of the compound Chinese herbal ointment.

[0032] Depend on Figure 2 From the results of Table 2, it can be seen that the composite Chinese herbal ointment prepared by the present invention has no obvious changes in the 6-month stability test, and the pH value fluctuates slightly, has excellent stability, and can be effectively stored for a long time; from the results of Comparative Example 3 and Example 2, it can be seen that the lack of chitosan-glycerophosphate system has a significant impact on the stability performance, the pH changes to a certain extent, and the appearance shows stratification and texture changes during long-term storage; from the results of Comparative Example 3 and Example 4, it can be seen that the lack of a buffer system leads to a gradual decrease in the pH value, and the appearance is also affected to a certain extent.

[0033] Skin irritation test: 6 healthy volunteers and 6 onychomycosis volunteers were selected and divided into three groups, with two healthy volunteers and two onychomycosis volunteers in each group. The composite Chinese herbal ointment prepared in Examples 1 to 3 was applied on their skin for a 48-hour patch test. The occurrence of allergic phenomena such as redness, swelling, and inflammation was observed at 24 hours and 48 hours, respectively. The results are shown in Table 3 below.

[0034] Table 3. Skin irritation test results of compound Chinese herbal ointment

[0035] It can be seen from the results in Table 3 that the composite Chinese herbal ointment prepared by the present invention has no obvious irritation to the skin and no adverse reactions, has excellent biocompatibility, can be effectively applied to the treatment of onychomycosis, and can form a stable gel layer in a relatively short time, effectively preventing the loss of drugs due to friction or washing.

[0036] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A composite Chinese herbal ointment for treating onychomycosis, characterized in that: The composition comprises active ingredients and matrix ingredients. The active ingredients comprise the following components in parts by weight: 10-20 parts of phellodendron, 10-20 parts of coptis root, 5-10 parts of sophora flavescens, 5-8 parts of dactylic acid, 5-10 parts of kochia scoparia, 5-8 parts of liquorice, 5-10 parts of cnidium monnieri, 5-10 parts of rhubarb, 3-5 parts of indigo, 3-5 parts of notoginseng powder, 20-30 parts of sesame oil, 1-2 parts of peppermint essential oil and 1-1.5 parts of eucalyptus essential oil; and the matrix ingredients comprise the following components in parts by weight: 8-12 parts of chitosan, 4-8 parts of disodium glycerophosphate, 2-3 parts of hydroxypropyl methylcellulose, 0.3-0.5 parts of potassium sorbate, 1-1.5 parts of citric acid, 1.5-2 parts of sodium citrate, 1-2 parts of emulsifier, 1-3 parts of moisturizer and 0.3-0.5 parts of antioxidant.

2. The composite Chinese herbal ointment for treating onychomycosis according to claim 1, characterized in that: The emulsifier is any one of lecithin, Tween-80 and Span-80.

3. The composite Chinese herbal ointment for treating onychomycosis according to claim 2, characterized in that: The moisturizing agent is any one of glycerin, propylene glycol and hyaluronic acid.

4. The composite Chinese herbal ointment for treating onychomycosis according to claim 3, characterized in that: The antioxidant is any one of vitamin E, tea polyphenols, butylated hydroxyanisole and propyl gallate.

5. A method for preparing the composite Chinese herbal ointment for treating onychomycosis according to any one of claims 1 to 4, characterized in that: The specific preparation steps are as follows: S1: clean and dry Phellodendron amurense, Coptis chinensis, Sophora flavescens, Dictamni cortex, Kochia scoparia, Licorice, Cnidium monnieri, Rhubarb, Indigo naturalis and Panax notoginseng powder, add them into acetic acid solution, stir and mix thoroughly, soak at room temperature, stir once every 6 hours, filter, centrifuge, filter, and obtain acetic acid extract; S2: adding the acetic acid extract prepared in step S1 into a vacuum concentration device, setting the temperature, stirring, and concentrating under vacuum to obtain a Chinese medicine concentrate; S3: adding citric acid and sodium citrate into deionized water, stirring and dissolving uniformly, to obtain a citric acid-sodium citrate buffer solution; Slowly drop the citric acid-sodium citrate buffer solution into the Chinese medicine concentrate prepared in step S2, and stir to mix evenly to obtain a mixed solution; S4: adding chitosan to the acetic acid solution, stirring and dissolving uniformly to obtain a chitosan solution; adding disodium glycerophosphate to the chitosan solution, stirring and dispersing uniformly to obtain a chitosan-glycerophosphate system; adding hydroxypropyl methylcellulose to deionized water, heating, stirring and dissolving uniformly to obtain a hydroxypropyl methylcellulose solution; S5: slowly adding the mixed solution prepared in step S3 to the chitosan-glycerophosphate system prepared in step S4, stirring and mixing evenly, then adding the hydroxypropyl methylcellulose solution prepared in step S4, stirring and mixing, and then slowly adding the emulsifier, stirring continuously, to obtain an emulsified matrix; S6: Slowly add sesame oil, peppermint essential oil and eucalyptus essential oil to the emulsified base prepared in step S5, stir and mix evenly, then add potassium sorbate, moisturizer and antioxidant in sequence, continue stirring and disperse evenly, and then homogenize to obtain a composite Chinese herbal ointment.

6. The method for preparing a composite Chinese herbal ointment for treating onychomycosis according to claim 5, characterized in that: In step S1, the amount of the acetic acid solution is 10 to 20 times the total weight of the substrate Chinese medicine.

7. The composite Chinese herbal ointment for treating onychomycosis according to claim 6, characterized in that: In step S3, the amount of deionized water used is 5 to 8 times the total weight of citric acid and sodium citrate.

8. The composite Chinese herbal ointment for treating onychomycosis according to claim 7, characterized in that: In step S4, the amount of the acetic acid solution used is 30 to 50 times the weight of the substrate chitosan.

9. The composite Chinese herbal ointment for treating onychomycosis according to claim 8, characterized in that: In step S6, the specific parameters of the homogenization treatment are: rotation speed 5000-6000 rpm, temperature 40-50°C, time 3-5 min, and the treatment is repeated 3 times.

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