Pharmaceutical composition containing high-molecular complex for external use on skin and preparation method of pharmaceutical composition

Abstract

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a pharmaceutical composition containing a high-molecular complex for external use on skin and a preparation method of the pharmaceutical composition, and the pharmaceutical composition comprises the following components in percentage by weight: 0.1-0.3% of sodium humate; 0.8 to 1.4% of a bacteriostatic composition; 0.8 to 1.4% of a soothing composition; 0.12 to 0.14 percent of chlorhexidine acetate; 6-20% of a humectant; 1-3% of an emulsifier; 0.1%-0.5% of a functional auxiliary material; the balance of pure water; the antibacterial composition comprises a glabrous sarcandra herb extract, a radix sophorae flavescentis extract and a fructus cnidii extract; the soothing composition comprises an earthworm extract and a fructus kochiae extract. The sodium humate is compounded with other components, so that the inhibition effect of the composition on microorganisms such as candida albicans, staphylococcus aureus and escherichia coli can be improved. Meanwhile, the sodium humate can effectively repair and relieve skin mucosa, so that the skin is quickly recovered to a healthy state.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, specifically relating to a pharmaceutical composition containing a high molecular weight complex for external use on the skin and its preparation method. Background Technology

[0002] Human skin acts as a protective barrier, preventing bacteria, fungi, and other microorganisms, as well as external pollutants, from invading the body and playing a vital role in maintaining health. However, prolonged contact with these microorganisms and pollutants can damage the skin, while bacteria and fungi can proliferate on the damaged surface, leading to dryness, itching, redness, swelling, and various inflammatory reactions, negatively impacting skin health and barrier function.

[0003] To relieve dryness, itching, redness, and inflammation of the skin, consumers often choose to use topical skin anti-inflammatory preparations. However, most topical skin preparations on the market have a narrow antibacterial range and focus only on inhibiting bacteria. They are not good at repairing damaged skin, and the skin remains susceptible to infection even after antibacterial treatment, which is not conducive to the recovery of skin health. Summary of the Invention

[0004] The technical problem to be solved by this invention is to provide a topical pharmaceutical composition containing a high molecular weight complex and its preparation method. This invention, through the compounding of sodium humate with other components, enhances the inhibitory effect of the composition on microorganisms such as Candida albicans, Staphylococcus aureus, and Escherichia coli, effectively improving skin problems such as papular urticaria, eczema, tinea pedis, perianal inflammation, and acne. It is also suitable for skin discomfort caused by damp heat, insect bites, and spicy irritants, demonstrating strong applicability. Simultaneously, sodium humate can effectively repair and soothe the skin and mucous membranes, allowing the skin to quickly return to a healthy state.

[0005] The technical solution adopted by the present invention to solve the above problems is as follows: A topical pharmaceutical composition containing a high molecular weight complex, comprising the following components by weight percentage: sodium humate 0.1–0.3%; antibacterial composition 0.8–1.4%; soothing composition 0.8–1.4%; chlorhexidine acetate 0.12–0.14%; moisturizer 6–20%; emulsifier 1–3%; functional excipients 0.1–0.5%; balance: purified water; The antibacterial composition includes extracts of *Smilax china*, *Sophora flavescens*, and *Cnidium monnieri*; the soothing composition includes extracts of *Earthworm* and *Kochia scoparia*.

[0006] Through the above technical solution, the carboxyl and hydroxyl groups contained in sodium humate can form stable complexes with alkaloids and flavonoids in the antibacterial extract, while simultaneously encapsulating chlorhexidine acetate. This not only enhances the stability of the active ingredients but also promotes transdermal absorption efficiency, avoiding performance degradation caused by interactions between components. Therefore, it strengthens the inhibitory effect of the composition of this invention on microorganisms such as Candida albicans, Staphylococcus aureus, and Escherichia coli. At the same time, sodium humate can effectively repair and soothe the skin and mucous membranes, allowing the skin to quickly return to a healthy state. Furthermore, the earthworm extract, Kochia scoparia extract, and moisturizers in the soothing composition further enhance the repair and soothing abilities of the composition of this invention, thereby promoting rapid skin recovery.

[0007] Furthermore, the mass ratio of the extracts of *Smilax glabra*, *Sophora flavescens*, and *Cnidium monnieri* in the antibacterial composition is 5:3:3.

[0008] Furthermore, the mass ratio of earthworm extract to Kochia scoparia extract in the soothing composition is 3:8.

[0009] Furthermore, the moisturizer includes at least one of tea oil and white petrolatum.

[0010] Through the aforementioned technical solutions, tea oil, rich in unsaturated fatty acids and vitamin E, can form a breathable moisturizing film on the skin surface, reducing moisture evaporation. Simultaneously, tea oil can penetrate the stratum corneum, replenishing lipid components, helping damaged skin repair its barrier, and improving dryness. White petrolatum, being an inert oil, forms a dense sealing film on the skin surface after application, blocking moisture exchange with the external environment and reducing transepidermal water loss. It is particularly suitable for skin problems such as eczema and tinea pedis accompanied by dryness and peeling, thus helping to maintain a moist environment on wounds and promoting healing. Furthermore, white petrolatum enhances the mildness of the composition, making it suitable for use on sensitive areas such as the perianal region and mucous membranes. In addition, white petrolatum is chemically stable and has good compatibility with ingredients such as sodium humate, antibacterial extracts, and chlorhexidine acetate, reducing the contact between the active ingredients and air and moisture, and lowering the risk of oxidative degradation.

[0011] Furthermore, the emulsifier includes at least one of glyceryl monostearate, PEG-100 stearate, potassium cetyl phosphate, and polysorbate-80.

[0012] Through the above technical solution, the selected emulsifier can not only improve the stability of the composition of the present invention and reduce the possibility of the composition of the present invention separating during storage, but also make the composition of the present invention have suitable consistency and fineness, so as to enhance its extensibility.

[0013] Furthermore, the functional excipients include at least one of menthol, bisabolol, and allantoin.

[0014] Through the above technical solutions, the menthol contained in peppermint can quickly bring a refreshing sensation to rapidly relieve itching, giving the composition an immediate soothing effect. Bisabolol not only inhibits inflammatory factors and relieves skin redness and burning sensation, but also improves the smoothness of the composition, enhancing its user experience. Allantoin softens the stratum corneum, allowing active ingredients to penetrate the skin surface more easily and accelerating the skin's recovery.

[0015] The present invention also provides a method for preparing the above-mentioned topical skin pharmaceutical composition containing a high molecular weight complex, comprising the following steps: S1. Wash the following herbs: *Euphorbia hirta*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*. Dry them at 35–50°C for 3–5 hours. After drying, pulverize them into ultrafine powders of 5–10 μm to obtain powders of *Euphorbia hirta*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, respectively. S2. Add pure water to the powders of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, respectively. The mass ratio of each powder to pure water is 1:8-10. After stirring evenly, extract by ultrasonication 2-3 times at 40-50℃. The ultrasonication frequency is 20-50kHz, and the ultrasonication time is 1-2h. After ultrasonication, filter the extract through a 0.45-1.0μm microporous membrane at an extraction and filtration pressure of 0.04-0.07MPa to obtain crude extracts of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, respectively. Combine the crude extracts of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, and then concentrate them to 10-15% of their original volume to obtain the extract. S3. Mix the humectant and emulsifier in a container and place it in a water bath at 55-65°C. Stir at 120-240 r / min until completely dissolved. After dissolution, keep warm for 30-60 min to obtain the oil phase. S4. Add sodium humate, chlorhexidine acetate, functional excipients, and pure water to another container, and stir at 120-240 r / min at room temperature until completely dissolved to obtain an aqueous phase; S5. Control the temperature of the aqueous phase and the oil phase to 35-45℃, then add the oil phase to the aqueous phase while stirring at a speed of 200-240 r / min. After mixing, continue stirring for 10-15 min, then add the extract while stirring, continue stirring for 5-8 min, and cool to room temperature to obtain the finished product.

[0016] Further, in step S2, the concentration is a rotary evaporation concentration, with a temperature of 25-30°C, a pressure of -0.02--0.08 MPa, and a rotation speed of 30-60 r / min.

[0017] The present invention has the following beneficial effects: 1. This invention, through the compounding of sodium humate with other components, enhances the inhibitory effect of the composition on microorganisms such as Candida albicans, Staphylococcus aureus, and Escherichia coli. It can effectively improve skin problems such as papular urticaria, eczema, tinea pedis, perianal inflammation, and acne. It is also suitable for skin discomfort caused by damp heat, insect bites, and spicy irritants, demonstrating strong applicability. Simultaneously, sodium humate can effectively repair and soothe the skin and mucous membranes, allowing the skin to quickly return to a healthy state.

[0018] 2. The complexation effect of sodium humate improves the stability of the active ingredient, further enhancing the effectiveness of the composition of the present invention.

[0019] 3. The composition of the present invention, through the synergistic effect between sodium humate and the soothing composition, enables the composition of the present invention to effectively repair skin damage and improve the health of the skin while inhibiting bacteria. Detailed Implementation

[0020] To make the technical problems, solutions, and advantages of this invention clearer, a detailed description will be provided below with reference to specific examples. However, the scope of protection of this invention is not limited to the following specific embodiments. The described embodiments are merely some, not all, of the embodiments of this invention, and are not intended to limit the invention. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0021] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art. The technical terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the invention.

[0022] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0023] In the quantitative experiments in the following examples, three replicate experiments were set up, and the data are the average of the three replicate experiments or the average ± standard deviation.

[0024] The pharmaceutical compositions of the present invention are provided in Examples 1-3 and Comparative Examples 1-6, respectively. The specific components and contents are shown in Table 1, in units of weight percentage.

[0025] Table 1

[0026] The preparation method of the above embodiments includes the following steps: S1. Wash the following herbs: *Euphorbia hirta*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*. Dry them at 40℃ for 4 hours. After drying, pulverize them into ultrafine powders to 10μm to obtain powders of *Euphorbia hirta*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, respectively. S2. Pure water was added to the powders of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, respectively. The mass ratio of each powder to pure water was 1:9. After stirring evenly, the mixture was ultrasonically extracted twice at 45℃. The ultrasonic frequency was 30kHz, and the ultrasonic time was 1.5h. After ultrasonication, the mixture was filtered through a 0.45μm microporous membrane at a pressure of 0.05MPa to obtain crude extracts of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*. The crude extracts of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri* were combined and then concentrated by rotary evaporation at 30℃, -0.05MPa, and 30r / min until the volume was reduced to 15% of the original volume, thus obtaining the extract. S3. Mix the humectant and emulsifier in a container and place it in a 60°C water bath. Stir at 120 r / min until completely dissolved. After dissolution, keep warm for 40 min to obtain the oil phase. S4. Add sodium humate, chlorhexidine acetate, functional excipients, and pure water to another container, and stir at 120 r / min at room temperature until completely dissolved to obtain an aqueous phase; S5. Control the temperature of the aqueous phase and the oil phase to 40℃, then add the oil phase to the aqueous phase while stirring at a speed of 240 r / min. After mixing, continue stirring for 10 min, then add the extract while stirring, continue stirring for 5 min, and cool to room temperature to obtain the finished product.

[0027] Experimental testing 1. Antibacterial test The antibacterial effects of the composition of the present invention against Candida albicans, Staphylococcus aureus and Escherichia coli were determined according to GB15979-2024. The test results are shown in Table 2.

[0028] Table 2

[0029] The test results of Examples 1-3 show that the composition of the present invention has excellent inhibitory effects on Candida albicans, Staphylococcus aureus, and Escherichia coli.

[0030] By comparing the test results of Example 2 and Comparative Example 1, it can be seen that the complexation effect of sodium humate can enhance the antibacterial effect of the composition of the present invention, thereby improving the effectiveness of the composition of the present invention.

[0031] A comparison of the test results of Example 2 and Comparative Examples 5-6 shows that adding too much or too little sodium humate will affect the antibacterial effect of the composition of the present invention. If the content is too low, the complexing effect of sodium humate cannot be fully utilized; if the content is too high, the composition of the present invention will become too viscous, affecting the dispersion of the active ingredients and thus affecting the antibacterial effect.

[0032] 2. Repair effect experiment Forty-five SPF-grade ICR mice were selected. After shaving the back of the mice, full-thickness skin defects were created using a 6mm diameter punch (one wound per mouse). The mice were randomly divided into nine groups of five mice each, corresponding to Examples 1-3 and Comparative Examples 1-6, respectively.

[0033] Administration method: Apply the sample (0.1g / wound) to the wound once daily for 14 consecutive days.

[0034] Observation indicators: On days 3, 7, 10 and 14 after administration, the wound area was measured using ImageJ software and the wound healing rate was calculated; the time to complete healing (scab shedding and new skin coverage) was recorded.

[0035] Wound healing rate: Healing rate (%) = [(Initial wound area - Wound area on the day) / Initial wound area] × 100%.

[0036] The specific test results are shown in Table 3.

[0037] Table 3

[0038] The test results of Examples 1-3 show that the composition of the present invention has excellent skin repair effect and can quickly restore the skin to a healthy state.

[0039] By comparing the test results of Example 2 with those of Comparative Examples 1-4, it can be seen that, compared to not adding any two or three of sodium humate, earthworm extract, and Kochia scoparia extract, the addition of sodium humate, earthworm extract, and Kochia scoparia extract can enhance the skin repair ability of the composition of the present invention, indicating that there is a synergistic effect among the three.

[0040] A comparison of the test results of Example 2 and Comparative Examples 5-6 shows that adding too much or too little sodium humate will affect the effectiveness of the composition of the present invention.

[0041] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0042] It should also be noted that the various specific technical features described in the above embodiments can be combined in any suitable manner without contradiction. To avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0043] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. A pharmaceutical composition containing a high molecular weight complex for external use, characterized in that, It comprises the following components by weight percentage: sodium humate 0.1–0.3%; antibacterial composition 0.8–1.4%; soothing composition 0.8–1.4%; chlorhexidine acetate 0.12–0.14%; humectant 6–20%; emulsifier 1–3%; functional excipients 0.1–0.5%; balance: purified water; The antibacterial composition includes extracts of *Smilax china*, *Sophora flavescens*, and *Cnidium monnieri*; the soothing composition includes extracts of *Earthworm* and *Kochia scoparia*.

2. The pharmaceutical composition containing a high molecular weight complex for topical use according to claim 1, characterized in that, The mass ratio of the extracts of *Smilax china*, *Sophora flavescens*, and *Cnidium monnieri* in the antibacterial composition is 5:3:

3.

3. The pharmaceutical composition containing a high molecular weight complex for topical use according to claim 1, characterized in that, The mass ratio of earthworm extract to Kochia scoparia extract in the soothing composition is 3:

8.

4. The pharmaceutical composition containing a high molecular weight complex for topical use according to claim 1, characterized in that, The moisturizer includes at least one of tea oil and white petrolatum.

5. The pharmaceutical composition containing a high molecular weight complex for topical use according to claim 1, characterized in that, The emulsifier includes at least one of glyceryl monostearate, PEG-100 stearate, potassium cetyl phosphate, and polysorbate-80.

6. The pharmaceutical composition containing a high molecular weight complex for topical application according to claim 1, characterized in that, The functional excipients include at least one of menthol, bisabolol, and allantoin.

7. The pharmaceutical composition containing a high molecular weight complex for topical use according to claim 1, characterized in that, The functional excipients include at least one of menthol, bisabolol, and allantoin.

8. A method for preparing a pharmaceutical composition according to any one of claims 1 to 7, characterized in that, Includes the following steps: S1. Wash the following herbs: *Euphorbia hirta*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*. Dry them at 35–50°C for 3–5 hours. After drying, pulverize them into ultrafine powders of 5–10 μm to obtain powders of *Euphorbia hirta*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, respectively. S2. Add pure water to the powders of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, respectively. The mass ratio of each powder to pure water is 1:8-10. After stirring evenly, extract by ultrasonication 2-3 times at 40-50℃. The ultrasonication frequency is 20-50kHz, and the ultrasonication time is 1-2h. After ultrasonication, filter the extract through a 0.45-1.0μm microporous membrane at an extraction and filtration pressure of 0.04-0.07MPa to obtain crude extracts of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, respectively. Combine the crude extracts of *Symplocos rubra*, *Pheretima aspergillum*, *Kochia scoparia*, *Sophora flavescens*, and *Cnidium monnieri*, and then concentrate them to 10-15% of their original volume to obtain the extract. S3. Mix the humectant and emulsifier in a container and place it in a water bath at 55-65°C. Stir at 120-240 r / min until completely dissolved. After dissolution, keep warm for 30-60 min to obtain the oil phase. S4. Add sodium humate, chlorhexidine acetate, functional excipients, and pure water to another container, and stir at 120-240 r / min at room temperature until completely dissolved to obtain an aqueous phase; S5. Control the temperature of the aqueous phase and the oil phase to 35-45℃, then add the oil phase to the aqueous phase while stirring at a speed of 200-240 r / min. After mixing, continue stirring for 10-15 min, then add the extract while stirring, continue stirring for 5-8 min, and cool to room temperature to obtain the finished product.

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