CN117138019A

CN117138019A - Composition for treating onychomycosis as well as preparation method and application thereof

Info

Publication number: CN117138019A
Application number: CN202311066800.9A
Authority: CN
Inventors: 伍晗; 杨鹏; 刘锐; 谭健兵; 张伟
Original assignee: Hunan Tiangenle Weijun Technology Co ltd
Current assignee: Hunan Tiangenle Weijun Technology Co ltd
Priority date: 2023-08-23
Filing date: 2023-08-23
Publication date: 2023-12-01

Abstract

The invention discloses a composition for treating onychomycosis, and a preparation method and application thereof, and relates to the technical field of pharmaceutical preparations. The composition comprises: beta-glucan, saccharomycetes polypeptide, cortex pseudolaricis extract and tea tree essential oil. The beta-glucan, the saccharomycete polypeptide, the cortex pseudolaricis extract and the tea tree essential oil have a certain synergistic effect, have good sterilization effects on fungi such as trichoderma rubrum and candida albicans, and have good onychomycosis treatment effect; meanwhile, the composition has no irritation, no obvious acute toxicity and good safety.

Description

Composition for treating onychomycosis as well as preparation method and application thereof

Technical Field

The invention relates to the technical field of pharmaceutical preparations, in particular to a composition for treating onychomycosis, and a preparation method and application thereof.

Background

Onychomycosis, the academic name onychomycosis, is a (finger, toe) nail infection caused by fungi such as dermatophytes, yeasts and molds. The nail is thickened, embrittled, loosened and hollow, and the surface is black, yellow, grey, white and the like.

At present, the treatment method of onychomycosis mainly comprises surgical nail removal, oral drug treatment and topical drug treatment. Surgical nail removal refers to removing a diseased nail plate by surgical means or chemical methods, which is easy to bring great pain to patients. Common oral therapeutic drugs include flavomycin, ketoconazole, fluconazole, itraconazole, terbinafine and the like, and most of the oral therapeutic drugs are antibiotics, so that drug resistance is easy to generate after long-term administration, and certain toxic and side effects can be generated. The external medicine comprises compound benzoic acid ointment, miconazole cream and the like, but has the defect of strong irritation.

Therefore, it is very important to provide a composition for external use which is non-irritating and has a good therapeutic effect on onychomycosis.

Disclosure of Invention

The present invention aims to solve at least one of the technical problems existing in the prior art. Therefore, the invention provides a composition for treating onychomycosis, which has no irritation and has better antibacterial effect on trichoderma viride and candida albicans.

The invention also provides a preparation method of the composition.

The invention also provides a medicine.

The invention also provides application of the composition in preparing a medicament for treating onychomycosis.

According to a first aspect of the present invention, an embodiment of a composition for treating onychomycosis comprises: beta-glucan, saccharomycetes polypeptide, cortex pseudolaricis extract and tea tree essential oil.

The composition according to the embodiment of the invention has at least the following beneficial effects:

in the composition of the embodiment, the cortex pseudolaricis extract and the tea tree essential oil beta-glucan, the saccharomycete polypeptide, the cortex pseudolaricis extract and the tea tree essential oil have a certain synergistic effect, have good sterilization effects on fungi such as trichoderma rubrum and candida albicans, and have good onychomycosis treatment effect. The composition has no irritation, no obvious acute toxicity, and good safety. The composition of the embodiment can also promote the barrier repair of damaged skin, is beneficial to the recovery of patients, and has good application prospect in fungal infection diseases such as onychomycosis and the like.

According to some embodiments of the invention, the method comprises the following steps in parts by weight: 3 to 11 parts of beta-glucan, 0.5 to 9 parts of saccharomycete polypeptide, 3 to 11 parts of cortex pseudolaricis extract and 4 to 10 parts of tea tree essential oil.

According to some embodiments of the invention, the method comprises the following steps in parts by weight: 5-9 parts of beta-glucan, 1-7 parts of saccharomycete polypeptide, 5-9 parts of cortex pseudolaricis extract and 6-8 parts of tea tree essential oil.

According to some embodiments of the invention, the method comprises the following steps in parts by weight: 8 parts of beta-glucan, 4 parts of saccharomycetes polypeptide, 5 parts of cortex pseudolaricis extract and 8 parts of tea tree essential oil.

According to some embodiments of the invention, the method comprises the following steps in parts by weight: 5 parts of beta-glucan, 7 parts of saccharomycetes polypeptide, 6 parts of cortex pseudolaricis extract and 7 parts of tea tree essential oil.

A method for preparing the above composition according to an embodiment of the second aspect of the present invention comprises the steps of:

mixing the beta-glucan, the saccharomycete polypeptide, the cortex pseudolaricis extract and the tea tree essential oil to obtain the composition.

According to a third aspect of the present invention, a medicament for treating onychomycosis comprises the composition. The medicine adopts all the technical schemes of the composition of the embodiment, so that the medicine has at least all the beneficial effects brought by the technical schemes of the embodiment.

According to some embodiments of the invention, the medicament further comprises pharmaceutically acceptable excipients.

According to some embodiments of the invention, the pharmaceutical dosage form is selected from a lotion, a liniment, a dressing, a paste or a spray.

According to some embodiments of the invention, the medicament may further comprise other medicaments having a onychomycosis treatment effect, preferably without affecting the effect of the composition.

Use of a composition as described above according to an embodiment of the fourth aspect of the invention for the preparation of a medicament for the treatment of onychomycosis.

Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.

Detailed Description

The conception and the technical effects produced by the present invention will be clearly and completely described in conjunction with the embodiments below to fully understand the objects, features and effects of the present invention. It is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments, and that other embodiments obtained by those skilled in the art without inventive effort are within the scope of the present invention based on the embodiments of the present invention.

The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.

In the description of the present invention, the terms "comprises" and "comprising," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.

When a range of values is disclosed herein, the range is considered to be continuous and includes both the minimum and maximum values for the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values of the range is included. Further, when multiple range description features or characteristics are provided, the ranges may be combined. In other words, unless otherwise indicated, all ranges disclosed herein are to be understood to include any and all subranges subsumed therein.

Unless otherwise indicated, the term "about" in the present invention means that the allowable error is within + -5%.

In the examples of the present invention, beta-glucan (lot number 2023041802) was purchased from Guangzhou Qian extract biotechnology Co., ltd;

yeast polypeptide (lot number 2023011401) was purchased from Guangzhou extract Biotech Co., ltd;

the cortex pseudolaricis extract was purchased from Siam Biotech Co., ltd;

tea tree essential oils were purchased from Jiangxi Kang Chengtang pharmaceutical company.

Example 1

The embodiment provides a composition for treating onychomycosis, which consists of beta-glucan, saccharomycete polypeptide, cortex pseudolaricis extract and tea tree essential oil. The formula is as follows in parts by weight:

a preparation method of a composition for treating onychomycosis comprises the following steps:

mixing beta-glucan, saccharomycete polypeptide, cortex pseudolaricis extract and tea tree essential oil to obtain the composition.

Example 2

Example 3

Comparative example 1

This comparative example provides a composition for treating onychomycosis, which is substantially the same as in example 1, except that: does not contain beta-glucan.

Comparative example 2

This comparative example provides a composition for treating onychomycosis, which is substantially the same as in example 1, except that: does not contain saccharomycete polypeptide.

Comparative example 3

This comparative example provides a composition for treating onychomycosis, which is substantially the same as in example 1, except that: does not contain cortex pseudolaricis extract.

Comparative example 4

This comparative example provides a composition for treating onychomycosis, which is substantially the same as in example 1, except that: does not contain tea tree essential oil.

Detection example 1

The skin irritation of the compositions of examples 1 to 3 and comparative examples 1 to 4 was examined. The detection method specifically comprises the following steps:

1. broken skin irritation experiments:

28 New Zealand white rabbits (14 females and males each, weight of 2.5 kg-3 kg) were randomly allocated to 7 groups of 4 animals (2 males and 2 females). Removing the fur on two sides of the spine of the back of the New Zealand white rabbit 24 hours before the test, wherein the fur removing range on two sides is about 2cm multiplied by 2cm; the skin portion of the pelt removed was marked with a "#" character by a sterilized scalpel until the skin surface bleeds. 0.5g of the compositions of examples 1 to 3 and comparative examples 1 to 4 were applied to one side of the dehaired bare skin, respectively, and the other side of the skin was not subjected to any treatment. Treatment was performed 1 time per day for 2 weeks, and before each treatment, the skin surface was cleaned of residual samples with water. After 1h of the last treatment, the skin condition was observed and a stimulus response score was performed as specified in reference to cosmetic safety Specification (2015).

2. Complete skin irritation experiments:

28 New Zealand white rabbits (14 females and males each, weight of 2.5 kg-3 kg) were randomly allocated to 7 groups of 4 animals (2 males and 2 females). The hairs on both sides of the spine of the New Zealand white rabbit are removed 24 hours before the test, and the hair removing range on both sides is about 2cm multiplied by 2cm. 0.5g of the compositions of examples 1 to 3 and comparative examples 1 to 4 were applied to one side of the dehaired bare skin, respectively, and the other side of the skin was not subjected to any treatment. Treatment was performed 1 time per day for 2 weeks, and before each treatment, the skin surface was cleaned of residual samples with water. After 1h of the last treatment, the skin condition was observed and a stimulus response score was performed as specified in reference to cosmetic safety Specification (2015).

The scoring results are shown in table 1.

TABLE 1

Note that: the scoring data shown in the table are all averaged.

The compositions of examples 1-3 and comparative examples 1-4 each scored 0 points for erythema and edema on the skin of the animals after treatment. This indicates that the compositions of examples 1 to 3 and comparative examples 1 to 4 have no skin irritation and have excellent safety.

Detection example 2

This test example detects acute toxicity of the skin of the compositions of examples 1 to 3. The detection method specifically comprises the following steps:

1. acute toxicity test of damaged skin:

16 New Zealand white rabbits (14 females and males each, weight of 2.5 kg-3 kg) were randomly allocated to 4 groups of 4 animals each (2 males and 2 females). Removing the back fur of the New Zealand white rabbits 24 hours before the test, wherein the hair removal range is about 3cm multiplied by 3cm; the skin portion of the pelt removed was marked with a "#" character by a sterilized scalpel until the skin surface bleeds. 1g of the compositions of examples 1 to 3 was applied to the pelt removing part, respectively, and treated 1 time per day for 1 week continuously, as an experimental group; before each treatment, the skin surface was cleaned of residual samples with water. New Zealand white rabbits treated with PBS were used as a control group. Daily recording food intake and body weight of each group of New Zealand white rabbits, and observing the physiological activity states of the groups of New Zealand white rabbits, such as respiration, activity, skin, hair, eyes and the like.

Compared with the control group, the New Zealand white rabbits in each experimental group have no obvious abnormality and no obvious change.

2. Complete skin acute toxicity experiment:

16 New Zealand white rabbits (14 females and males each, weight of 2.5 kg-3 kg) were randomly allocated to 4 groups of 4 animals each (2 males and 2 females). The back of New Zealand white rabbits were dehaired 24 hours before the test, and the dehairing range was about 3cm×3cm. 1g of the compositions of examples 1 to 3 was applied to the pelt removing part, respectively, and treated 1 time per day for 1 week continuously, as an experimental group; before each treatment, the skin surface was cleaned of residual samples with water. New Zealand white rabbits treated with PBS were used as a control group. Daily recording food intake and body weight of each group of New Zealand white rabbits, and observing the physiological activity states of the groups of New Zealand white rabbits, such as respiration, activity, skin, hair, eyes and the like.

In conclusion, the compositions of examples 1 to 3 have no obvious adverse reaction or toxic or side effect and have good safety.

Detection example 3

The present test example examined the in vitro bacteriostatic effects of the compositions of examples 1 to 3 and comparative examples 1 to 4. The detection method specifically comprises the following steps:

1) Simulating human nails by using cow hoof slices with the thickness of about 0.25mm, the length of about 10m and the width of about 5mm, and sterilizing for later use; adjusting the activated Trichophyton rubrum and Candida albicans to bacterial concentration of 10 with YPD medium ⁷ CFU/mL, obtain the trichoderma reesei bacterial suspension and candida albicans bacterial suspension respectively; dropwise adding 10 mu L of trichoderma reesei bacterial suspension onto the beef hooves, and airing the bacterial suspension to obtain a onychomycosis model A; dripping 10 mu L of candida albicans suspension on the beef hooves, and airing the suspension to obtain a onychomycosis model B;

2) Randomly dividing 24 onychomycosis models A into 8 groups; wherein 3 groups of the compositions of examples 1 to 3 are respectively coated on the cow hooves, and 4 groups of the compositions of comparative examples 1 to 4 are respectively coated on the cow hooves, and the compositions are experimental groups; one group was treated without any treatment as a control group. Randomly dividing 24 onychomycosis models B into 8 groups; wherein 3 groups of the compositions of examples 1 to 3 are respectively coated on the cow hooves, and 4 groups of the compositions of comparative examples 1 to 4 are respectively coated on the cow hooves, and the compositions are experimental groups; one group was treated without any treatment as a control group. After being treated for 20min at the temperature of 28 ℃, each cow hoof slice is respectively placed in 1mL of physiological saline, and is oscillated for 10min, so that bacteria on the cow hoof slice are separated from the surface of the cow hoof slice; colony counting is carried out through multiple dilution, and the sterilization rate is calculated;

wherein, the sterilization rate (%) = (1-experimental group colony count/control group colony count) ×100%.

The test results are shown in Table 2.

TABLE 2

The compositions of examples 1-3 have good antibacterial and bactericidal effects on trichophyton rubrum and candida albicans. Any one of the default beta-glucan, the saccharomycete polypeptide, the cortex pseudolaricis extract and the tea tree essential oil can cause the in-vitro antibacterial effect to be greatly reduced. This indicates that the four have a certain synergistic effect.

Detection example 4

(1) Case selection:

80 informed consent patients diagnosed with onychomycosis were selected, ranging in age from 20 years to 55 years, 40 men and 40 women.

(2) The treatment method comprises the following steps:

80 patients were randomly divided into 8 groups of 10 patients, each group being comparable with the compositions of examples 1-3 and comparative examples 1-4, commercially available terbinafine hydrochloride cream, with no significant differences in statistical treatment (P > 0.05) in age, sex, disease condition, etc.

Each group is smeared with the corresponding medicines with the same quantity on the affected part, the medicine is changed for 1 to 2 times every day, and any other treatment is stopped during the treatment period. The effect was observed after 1 month.

(3) And (3) judging curative effect:

and (3) healing: the diseased nails disappear, most of the new nails grow out, and no itch exists;

the method is effective: part of nails grow out, become crisp and improved, are not separated from the nail bed, and are free from moth-eating voids and itching;

invalidation: the symptoms have no obvious change after the administration compared with the prior treatment.

The treatment results are shown in table 3.

TABLE 3 Table 3

The compositions of examples 1-3 have good onychomycosis treatment effect, and the total recovery rate and the effective rate are better than those of the terbinafine hydrochloride cream sold in the market. Whereas any of the default beta-glucan, yeast polypeptide, cortex pseudolaricis extract and tea tree essential oil will result in a substantial reduction in therapeutic efficacy.

The embodiments of the present invention have been described in detail with reference to the embodiments, but the present invention is not limited to the embodiments, and various changes can be made within the knowledge of those skilled in the art without departing from the spirit of the present invention.

Claims

1. A composition for treating onychomycosis, comprising: beta-glucan, saccharomycetes polypeptide, cortex pseudolaricis extract and tea tree essential oil.

2. The composition of claim 1, comprising, in parts by weight: 3 to 11 parts of beta-glucan, 0.5 to 9 parts of saccharomycete polypeptide, 3 to 11 parts of cortex pseudolaricis extract and 4 to 10 parts of tea tree essential oil.

3. The composition according to claim 2, characterized by comprising, in parts by weight: 5-9 parts of beta-glucan, 1-7 parts of saccharomycete polypeptide, 5-9 parts of cortex pseudolaricis extract and 6-8 parts of tea tree essential oil.

4. The composition of claim 1, comprising, in parts by weight: 8 parts of beta-glucan, 4 parts of saccharomycetes polypeptide, 5 parts of cortex pseudolaricis extract and 8 parts of tea tree essential oil.

5. The composition of claim 1, comprising, in parts by weight: 5 parts of beta-glucan, 7 parts of saccharomycetes polypeptide, 6 parts of cortex pseudolaricis extract and 7 parts of tea tree essential oil.

6. The composition of claim 1, comprising, in parts by weight: 9 parts of beta-glucan, 1 part of saccharomycete polypeptide, 9 parts of cortex pseudolaricis extract and 6 parts of tea tree essential oil.

7. A process for the preparation of a composition as claimed in any one of claims 1 to 6, comprising the steps of:

8. A medicament for treating onychomycosis, comprising a composition according to any one of claims 1 to 6.

9. The medicament of claim 8, further comprising a pharmaceutically acceptable excipient.

10. Use of a composition according to any one of claims 1 to 6 for the preparation of a medicament for the treatment of onychomycosis.