A composition for preventing and treating cheilitis and a preparation method thereof

Abstract

The invention belongs to the technical field of cheilitis prevention and treatment, and in particular relates to a composition for preventing and treating cheilitis and a preparation method thereof. The composition comprises the following components and raw materials: 20-50 parts by weight of Sophora flavescens, 10-30 parts by weight of Lithospermum officinale, 1-3 parts by weight of Sichuan pepper, 100-200 parts by volume of olive oil, 100-200 parts by volume of animal fat, and 200-400 parts by volume of vaseline, wherein when the weight unit is g, the volume unit is mL. The ointment of the invention can not only effectively treat dry and chapped lip skin, but also further improve the antioxidant capacity of local skin, thereby achieving both prevention and treatment.

Description

Technical Field

[0001] The invention belongs to the technical field of cheilitis prevention and treatment, and in particular relates to a composition for preventing and treating cheilitis and a preparation method thereof. Background Art

[0002] Cheilitis is a general term for inflammatory diseases of the lips, characterized by dryness, scaling, cracking, pain, itching, erosion, exudation, and even bleeding. Cheilitis is categorized into various types, including angular cheilitis, actinic cheilitis, contact cheilitis, plasma cell cheilitis, glandular cheilitis, granulomatous cheilitis, exfoliative cheilitis, and factitious cheilitis. Plateaus, characterized by long hours of sunshine, strong ultraviolet rays, and dry air, increase the vulnerability of the delicate skin of the lips to prolonged exposure to these harsh conditions. To highlight its characteristics, we refer to cheilitis occurring in plateau areas as "highland cheilitis." Yan Jianfei et al. found that the incidence of plateau cheilitis is significantly higher than at lower altitudes, with dry and desquamative cheilitis and actinic cheilitis being more common. In 1991, Zhang Rong et al. conducted an epidemiological survey of 134 cases of cheilitis at four locations between 4,300 and 5,380 meters above sea level, finding a prevalence of 70.9%, with dry and desquamative cheilitis accounting for 49.2% and eczematous and erosive cheilitis accounting for 21.7%. In 2006, Liu Yong et al. conducted an epidemiological survey of 706 men in Lhasa, finding a prevalence of dry and desquamative cheilitis of 59.6%. A 2008-2010 epidemiological survey by Sun Zhengqi et al. on young people in the Tibet Autonomous Region found a prevalence of 13.4%, with a significantly higher prevalence in men than in women. Cheilitis can be acute or chronic. Many cases of acute cheilitis develop repeatedly, lasting for months or even years without resolution, leading to chronic cheilitis, which can cause significant psychological stress and extreme suffering for patients.

[0003] In the existing technology, prednisone acetate, triamcinolone acetonide, chloroquine phosphate, vitamin oil (emulsion), niacinamide lip balm and other drugs or care products are often used clinically to improve symptoms. However, some of these drugs are not suitable for daily long-term use, and there is very little research on traditional Chinese medicine products, and no effective and fixed formula has been established. Summary of the Invention

[0004] In order to solve the above technical problems, the present invention provides a composition for preventing and treating cheilitis and a preparation method thereof.

[0005] The technical solution of the present invention to solve the above technical problems is as follows: a composition for preventing and treating cheilitis, characterized in that it comprises the following components and raw materials:

[0006] 20-50 parts by weight of Sophora flavescens, 10-30 parts by weight of Lithospermum officinale, 1-3 parts by weight of Sichuan pepper, 100-200 parts by volume of olive oil, 100-200 parts by volume of animal fat and 200-400 parts by volume of vaseline, wherein when the weight measurement unit is g, the volume measurement unit is mL.

[0007] Preferably, the following raw materials are included:

[0008] 25 parts by weight of Sophora flavescens, 15 parts by weight of Lithospermum officinale, 1 part by weight of Sichuan pepper, 100 parts by volume of olive oil, 100 parts by volume of animal fat and 300 parts by volume of vaseline, wherein, when the weight measurement unit is g, the volume measurement unit is mL.

[0009] Preferably, the animal fat is rendered lard.

[0010] The present invention also provides a method for preparing a composition for preventing and treating cheilitis, wherein the composition is in the form of an ointment, and the preparation method comprises the following steps:

[0011] 1) Pour olive oil and animal fat into a container and heat, maintaining the oil temperature at 60-80°C until the animal fat is completely melted to obtain a mixed oil;

[0012] 2) adding Sophora flavescens to the mixed oil obtained in step 1), heating until the oil bubbles, maintaining this temperature for about 20 minutes, or until the Sophora flavescens is completely browned, filtering to remove the residue, and obtaining medicinal oil A;

[0013] 3) When the medicinal oil A cools to 70-80°C, add Sichuan peppercorns and maintain the oil temperature at 70-80°C until the surface of the Sichuan peppercorns turns black. Filter and remove the residue to obtain medicinal oil B;

[0014] 4) Cooling the medicinal oil B obtained in step 3) to 55-60° C., pouring in lithospermum erythrorhizon, controlling the medicinal oil B to produce small bubbles, and continuously stirring until the lithospermum erythrorhizon is completely immersed in the oil, turning off the heat, and letting it stand for 3-7 days to more fully extract the drug, filtering and removing the residue to obtain medicinal oil C;

[0015] 5) heating the medicinal oil C obtained in step 4), adding vaseline, maintaining the temperature not higher than 80° C., stirring until the vaseline and medicinal oil C are completely blended, dividing into containers, and refrigerating to obtain an ointment.

[0016] The pharmacological analysis of each component in the composition of the present invention is as follows:

[0017] Sophora flavescens, known for its cold and bitter properties, has the effects of clearing heat and cooling blood, dispelling wind, and killing insects. Its chemical composition is complex and diverse, primarily comprising alkaloids, flavonoids, triterpenoid saponins, lignans, and other compounds. Matrine in Sophora flavescens can disrupt bacterial capsules, inhibit bacterial density sensing systems, and influence biofilm formation. It directly binds to bacterial proteins, causing bacterial death, thereby achieving broad-spectrum antibacterial effects. A Sophora flavescens aqueous extract can reduce skin swelling in guinea pigs and decrease serum levels of the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while increasing levels of the anti-inflammatory cytokine IL-10. Its mechanism of action is to suppress inflammation by modulating the immune response, inhibiting the expression of the transcription factor RORγt and thereby reducing Th17 differentiation. It also exerts anti-inflammatory effects by activating the Nrf2 / HO-1 pathway. Matrine achieves its antiviral effect by activating host cell interferon (IFN), inhibiting the NF-κB signaling pathway, reducing the activity of extracellular regulated protein kinase (ERK) and its phosphorylation level, and reversibly binding to the active center of viral DNAP.

[0018] Lithospermum officinale is cold in nature, sweet and salty in taste, and enters the heart and liver meridians, with the effect of stopping bleeding and cooling blood. The chemical composition of Lithospermum officinale is very complex, mainly composed of a variety of components such as naphthoquinones, terpene phenols and benzoquinones, phenolic acids and their salts, alkaloids, aliphatic and ester compounds. Compounds such as shikonin, deoxyshikonin, β-dimethylpropylenephthaloshikonin, and methylshikonin in Lithospermum officinale have inhibitory effects on various tumors. It has been shown that lithospermum polysaccharides extracted from Lithospermum officinale root decoction can enhance the phagocytic function of macrophages and promote the number and function of T lymphocytes. Acetylshikonin and shikonin showed significant antioxidant activity when tested using an oil oxidation stability tester.

[0019] Sichuan pepper is warm in nature and pungent in flavor, and enters the stomach, spleen, and kidney meridians. Its medicinal properties and efficacy are closely related to its color, aroma, and texture. Its red color enters the heart, nourishes the blood, and dispels blood stasis. Its warm nature enters the kidneys to replenish fire and generate new blood. Its warm water nourishes the earth, warms the middle, and strengthens the spleen to aid blood circulation. Sichuan pepper is a plant used both as a medicine and a food, containing bioactive substances with medicinal value, such as volatile oils, amides, alkaloids, flavonoids, lignans, and coumarins. It has multiple pharmacological effects, including antioxidant, anti-tumor, analgesic, antibacterial, and anti-inflammatory properties. Its volatile oil has a good permeation-enhancing effect and can reduce skin irritation.

[0020] Olive polyphenols in olive oil have the effects of promoting cellular oxygen metabolism, resisting lipid peroxidation, and resisting oxidative DNA damage. At the same time, active substances such as superoxide dismutase, vitamin C and polysaccharides in olive oil have the activity of eliminating superoxide anion free radicals in the human body, which has anti-aging and immune function enhancement effects. It can increase the activity of red blood cells and SOD in the blood of the elderly and reduce the content of lipid peroxides.

[0021] Refined lard is rich in triglycerides, fatty acids, and trace elements and minerals necessary for skin metabolism, which can moisturize, nourish, and restore elasticity to the skin.

[0022] Vaseline, a refined form of petroleum jelly, is a mixture of residual oil wax and lubricating oil. Its scientific name is petroleum jelly. It is a chemically inert hydrocarbon and an essential ingredient in cosmetics, ointments, and medical excipients. When applied to the skin, it forms a somewhat occlusive oil film on the stratum corneum, reducing moisture evaporation and providing a moisturizing effect. It also prevents chapped skin and itching caused by insufficient sebum secretion. Olive oil, rich in squalene, unsaturated fatty acids, various vitamins (A, D, E, K, etc.), and phenolic antioxidants, has antioxidant, moisturizing, anti-chapped, anti-inflammatory, and antiviral properties.

[0023] The combined use of the above-mentioned drugs and excipients makes the entire formula have anti-inflammatory, antioxidant, antiviral and skin moisturizing effects.

[0024] The beneficial effects of the present invention are:

[0025] 1. The present invention's Sophora flavescens, Lithospermum officinale, Sichuan pepper, olive oil, animal fat and vaseline are used in combination, so that the composition of the present invention has anti-inflammatory, antioxidant, antiviral and skin-moisturizing effects;

[0026] 2. In the preparation process, olive oil and animal fat mixture is first used in batches and at low temperature to extract the drugs in the formula, and then vaseline is used as an excipient to obtain the ointment; olive oil and refined lard mixture is used to extract lithospermum at low temperature to improve the extraction of active ingredients. At the same time, the refined lard itself can serve as a part of the medicine to play a role in moisturizing and nourishing.

[0027] 3. The Chinese medicinal materials in the composition of the present invention have the effects of clearing heat and cooling blood, promoting blood circulation and stopping bleeding; Sophora flavescens has the effects of anti-inflammatory, analgesic, antiviral and immune enhancement; Lithospermum erythrorhizon has the effects of anti-inflammatory, antiviral and anti-allergic; Sichuan pepper has the effects of antibacterial, analgesic and strong antioxidant. The ointment developed can form a stable medicinal oil protective film on the surface of the lip skin, reduce the volatilization of water, enhance the antioxidant capacity of skin cells, and provide the skin surface cells with essential amino acids and trace elements, thereby playing the role of moisturizing, anti-chapped, anti-inflammatory and antiviral, thereby achieving the goal of prevention and treatment in one. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a rat skin image after external application of the ointment according to Example 1 of the present invention.

[0029] in, Figure 1 (a) is the skin picture of rats in the normal group. Figure 1 (b) is the skin picture of rats in the 2-fold 1-week group. Figure 1 (c) is the skin picture of rats in the 2-fold 2-week group. Figure 1 (d) is the skin picture of rats in the 5-times 1-week group. Figure 1 (e) is the skin image of rats in the 5-fold 2-week group;

[0030] Figure 2 This is the HE staining picture of rat skin after external application of the ointment of Example 1 of the present invention.

[0031] in, Figure 2 (a) HE staining of the skin of rats in the normal group. Figure 2 (b) HE staining of rat skin in the 2-fold 1-week group. Figure 2 (c) is the HE staining picture of the skin of rats in the 2-fold 2-week group. Figure 2 (d) is the HE staining picture of the rat skin in the 5-fold 1-week group. Figure 2 (e) HE staining of the skin of rats in the 5x 2-week group;

[0032] Figure 3 This is the HE staining image of rat liver after external application of the ointment of Example 1 of the present invention.

[0033] in, Figure 3 (a) HE staining of the liver of rats in the normal group. Figure 3 (b) HE staining of the liver of rats in the 2-fold 1-week group. Figure 3 (c) HE staining of the liver of rats in the 2-week group. Figure 3 (d) HE staining of the liver of rats in the 5-fold 1-week group. Figure 3 (e) HE staining of the liver of rats in the 5x 2-week group;

[0034] Figure 4 This is the HE staining image of rat kidney after external application of the ointment of Example 1 of the present invention.

[0035] in, Figure 4 (a) HE staining of the kidney of rats in the normal group. Figure 4 (b) HE staining of the kidneys of rats in the 2-fold 1-week group. Figure 4 (c) HE staining of the kidneys of rats in the 2-fold 2-week group. Figure 4 (d) is the HE staining image of the kidney of rats in the 5-fold 1-week group. Figure 4 (e) HE staining of the kidneys of rats in the 5x 2-week group;

[0036] Figure 5 This is the change diagram of case 1 before and after treatment;

[0037] Figure 6 This is the change diagram of case 2 before and after treatment;

[0038] Figure 7 This is the change diagram of case 3 before and after treatment;

[0039] Figure 8 This is the change diagram of case 4 before and after treatment;

[0040] Figure 9 This is a graph showing the changes in Case 5 before and after treatment. DETAILED DESCRIPTION

[0041] The principles and features of the present invention are described below. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0042] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0043] A composition for preventing and treating cheilitis, comprising the following components and raw materials:

[0044] 20-50 parts by weight of Sophora flavescens, 10-30 parts by weight of Lithospermum officinale, 1-3 parts by weight of Sichuan pepper, 100-200 parts by volume of olive oil, 100-200 parts by volume of animal fat and 200-400 parts by volume of vaseline, wherein when the weight measurement unit is g, the volume measurement unit is mL.

[0045] Preferably, the following raw materials are included:

[0046] 25 parts by weight of Sophora flavescens, 15 parts by weight of Lithospermum officinale, 1 part by weight of Sichuan pepper, 100 parts by volume of olive oil, 100 parts by volume of animal fat and 300 parts by volume of vaseline, wherein, when the weight measurement unit is g, the volume measurement unit is mL.

[0047] Preferably, the animal fat is rendered lard.

[0048] Specifically, the preparation process of refined lard is as follows: fresh lard is refined by wet method at a temperature of 110° C. and a pressure of 0.06 MPa for 40 minutes.

[0049] In the composition of the present invention, sophora flavescens and lithospermum officinale are main drugs, Sichuan pepper is a secondary drug, and vaseline, olive oil and refined lard are excipient drugs.

[0050] The present invention also provides a method for preparing a composition for preventing and treating cheilitis, wherein the composition is in the form of an ointment, and the preparation method comprises the following steps:

[0051] 1) Pour olive oil and animal fat into a container and heat, maintaining the oil temperature at 60-80°C until the animal fat is completely melted to obtain a mixed oil;

[0052] 2) adding Sophora flavescens to the mixed oil obtained in step 1), heating until the oil bubbles, maintaining this temperature for about 20 minutes, or until the Sophora flavescens is completely browned, filtering to remove the residue, and obtaining medicinal oil A;

[0053] 3) When the medicinal oil A cools to 70-80°C, add Sichuan peppercorns and maintain the oil temperature at 70-80°C until the surface of the Sichuan peppercorns turns black. Filter and remove the residue to obtain medicinal oil B;

[0054] 4) Cooling the medicinal oil B obtained in step 3) to 55-60° C., pouring in lithospermum erythrorhizon, controlling the medicinal oil B to produce small bubbles, and continuously stirring until the lithospermum erythrorhizon is completely immersed in the oil, turning off the heat, and letting it stand for 3-7 days to more fully extract the drug, filtering and removing the residue to obtain medicinal oil C;

[0055] 5) heating the medicinal oil C obtained in step 4), adding vaseline, maintaining the temperature not higher than 80° C., stirring until the vaseline and medicinal oil C are completely blended, dividing into containers, and refrigerating to obtain an ointment.

[0056] Compared with the prior art, the existing lithospermum extraction (lithospermum paste preparation) is mostly high-temperature frying, and shikonin begins to decompose when the temperature exceeds 100°C. The present invention uses a mixture of olive oil and refined lard to extract lithospermum at low temperature, thereby improving the extraction of effective ingredients. At the same time, the refined lard itself can be used as a part of the medicine to play a role in moisturizing and nourishing.

[0057] Sophora flavescens has anti-inflammatory, analgesic, antiviral and immune-enhancing effects, Lithospermum erythrorhizon has anti-inflammatory, antiviral and anti-allergic effects, Sichuan pepper has antibacterial, analgesic and strong antioxidant effects. The ointment developed can form a stable medicinal oil protective film on the surface of the lip skin, which can reduce the volatilization of water, enhance the antioxidant capacity of skin cells, and provide essential amino acids and trace elements for the skin surface cells, thereby playing a role in moisturizing, anti-chapped, anti-inflammatory and antiviral, thereby achieving prevention and treatment in one.

[0058] The following detailed description of a composition for preventing and treating cheilitis and its preparation method is provided in conjunction with the following examples and experimental data. It should be understood that these examples are intended to illustrate the present application only and are not intended to limit the scope of the present application. Experimental methods in the following examples, where specific conditions are not specified, are generally determined in accordance with national standards. Where no corresponding national standards are available, the methods were performed in accordance with commonly used international standards, conventional conditions, or conditions recommended by the manufacturer.

[0059] Example 1

[0060] Pour 100 mL of olive oil and 100 mL of melted refined lard into a stainless steel container and heat it on an induction cooker, maintaining the oil temperature at 60-80°C to obtain a mixed oil; heat the mixed oil until small bubbles appear, add 25 g of Sophora flavescens, maintain this temperature for 20 minutes until the Sophora flavescens is completely browned, filter and remove the residue to obtain medicinal oil A; when the medicinal oil A is cooled to 70-80°C, add 1 g of Sichuan pepper, maintain the oil temperature at 70-80°C until the surface of the Sichuan pepper turns black, filter and remove the residue to obtain medicinal oil B; when the medicinal oil B is cooled to 55-60°C, pour 15 g of Lithospermum erythrorhizon, control the small bubbles of the medicinal oil B, continue stirring until the Lithospermum erythrorhizon is completely immersed in the oil, turn off the heat, let it stand for 3-7 days, filter and remove the residue to obtain medicinal oil C; heat the medicinal oil C, add 300 mL of melted vaseline, maintain the temperature not higher than 80°C, stir until the vaseline and medicinal oil C are completely fused, divide them into device containers, refrigerate, and obtain an ointment.

[0061] Example 2

[0062] Pour 200mL of olive oil and 100mL of refined lard into a stainless steel container and place it on an induction cooker for heating, maintaining the oil temperature at 60-80°C to obtain a mixed oil; heat the mixed oil until small bubbles appear, add 50g of Sophora flavescens, maintain this temperature for 20 minutes, until the Sophora flavescens is completely browned, filter and remove the residue to obtain medicinal oil A; when the medicinal oil A is cooled to 70-80°C, add 2g of Sichuan pepper, maintain the oil temperature at 70-80°C until the surface of the Sichuan pepper turns black, filter and remove the residue to obtain medicinal oil B; when the medicinal oil B is cooled to 55-60°C, pour 30g of Lithospermum erythrorhizon, control the medicinal oil B to produce small bubbles, continue stirring until the Lithospermum erythrorhizon is completely immersed in the oil, turn off the heat, let it stand for 3-7 days, filter and remove the residue to obtain medicinal oil C; heat the medicinal oil C, add 300mL of vaseline, maintain the temperature not higher than 80°C, stir until the vaseline and medicinal oil C are completely fused, divide them into device containers, refrigerate, and obtain an ointment.

[0063] Example 3

[0064] Pour 100mL of olive oil and 200mL of refined lard into a stainless steel container and place it on an induction cooker for heating, maintaining the oil temperature at 60-80°C to obtain a mixed oil; heat the mixed oil until small bubbles appear, add 50g of Sophora flavescens, maintain this temperature for 20 minutes, until the Sophora flavescens is completely browned, filter and remove the residue to obtain medicinal oil A; when the medicinal oil A is cooled to 70-80°C, add 2g of Sichuan pepper, maintain the oil temperature at 70-80°C until the surface of the Sichuan pepper turns black, filter and remove the residue to obtain medicinal oil B; when the medicinal oil B is cooled to 55-60°C, pour 30g of Lithospermum erythrorhizon, control the medicinal oil B to produce small bubbles, continue stirring until the Lithospermum erythrorhizon is completely immersed in the oil, turn off the heat, let it stand for 3-7 days, filter and remove the residue to obtain medicinal oil C; heat the medicinal oil C, add 300mL of vaseline, maintain the temperature not higher than 80°C, stir until the vaseline and medicinal oil C are completely fused, divide them into device containers, refrigerate, and obtain an ointment.

[0065] Comparative Example 1

[0066] Pour 300 mL of olive oil into a stainless steel container and place it on an induction cooker and heat until the oil bubbles up. Add 50 g of Sophora flavescens and maintain this temperature for 20 minutes until the Sophora flavescens is completely browned. Filter and remove the residue to obtain medicated oil A. When medicated oil A cools to 70-80°C, add 2 g of Sichuan pepper and maintain the oil temperature at 70-80°C until the surface of the Sichuan pepper turns black. Filter and remove the residue to obtain medicated oil B. When medicated oil B cools to 55-60°C, pour in 30 g of Lithospermum erythrorhizon, control the bubbling of medicated oil B, continue stirring until the Lithospermum erythrorhizon is completely immersed in the oil, turn off the heat, let it stand for 3-7 days, filter and remove the residue to obtain medicated oil C. Heat medicated oil C, add 900 mL of vaseline, keep the temperature no higher than 80°C, stir until the vaseline and medicated oil C are completely fused, divide into device containers, and refrigerate to obtain an ointment.

[0067] Comparative Example 2

[0068] Pour 300mL of refined lard into a stainless steel container and place it on an induction cooker and heat until the oil bubbles up. Add 50g of Sophora flavescens and maintain this temperature for 20 minutes until the Sophora flavescens is completely browned. Filter and remove the residue to obtain medicinal oil A; when the medicinal oil A is cooled to 70-80℃, add 2g of Sichuan pepper and maintain the oil temperature at 70-80℃ until the surface of the Sichuan pepper turns black. Filter and remove the residue to obtain medicinal oil B; when the medicinal oil B is cooled to 55-60℃, pour 30g of Lithospermum erythrorhizon, control the medicinal oil B to bubble up, continue stirring until the Lithospermum erythrorhizon is completely immersed in the oil, turn off the heat, let it stand for 3-7 days, filter and remove the residue to obtain medicinal oil C; heat the medicinal oil C, add 900mL of vaseline, maintain the temperature no higher than 80℃, stir until the vaseline and medicinal oil C are completely fused, divide them into containers, refrigerate, and obtain an ointment.

[0069] Test example

[0070] 1. Performance Evaluation

[0071] 1. The ointments prepared in Examples 1-3 and Comparative Examples 1-2 were subjected to assay of the contents of Radix Lithospermi and Radix Sophorae Flavescentis. The assay results are shown in the following table:

[0072] Table 1 Results of determination of active ingredient content

[0073]

[0074] As can be seen from Table 1, the ointments prepared by the above-mentioned preparation method have higher contents of the active ingredients of Sophora flavescens and Lithospermum erythrorhizon extracted in Examples 1, 2 and 3. Comparative Example 2 uses refined lard alone as a solvent, and the obtained Lithospermum erythrorhizon and Sophora flavescens contents are the lowest among the groups. Although the matrine content in Comparative Example 1 is higher than that in the other groups, the L-shikonin content is lower than that in the other groups, indicating that the yield of the active ingredients in the Chinese medicine composition in the above-mentioned preparation method is higher, and that the quality of the Chinese medicine ointment is good.

[0075] 2. Evaluation of moisture retention, heat resistance and cold resistance

[0076] (1) Moisturizing evaluation:

[0077] Test population: 20 healthy adults with no history of skin diseases, random gender, randomly divided into 4 groups, 5 people in each group.

[0078] Test method: The test was conducted on a 4.0×4.0 cm area of skin on the inner left and right forearms of the subjects. The subjects ensured that no cosmetics with similar functions were used on the test areas within 2 days prior to the test. The test was conducted in a room at a temperature of 25°C and a relative humidity of 61%. The test areas were first cleaned with alkaline soap, rinsed thoroughly, and then air-dried. The ointment of Example 1 was applied to the left arms of the test subjects in Groups 1 to 4, and the ointments of Examples 2-3 and Comparative Examples 1-2 were applied to the right arms of the test subjects in Groups 1 to 4, respectively. The skin moisture content (MMV) value (Corneometer CM 825, CK GmbH, Germany) and the skin surface water loss (TEWL) value (Tewameter™ 300, CK GmbH, Germany) were measured before application of the ointments and 10 minutes, 30 minutes, 60 minutes, and 120 minutes after application.

[0079] The results showed that the skin moisture content MMV value of the ointment in Example 1 increased, and the moisturizing effect was better than that of the product ointments in Examples 2-3 and Comparative Examples 1-2.

[0080] (2) Heat resistance test: The products of Examples 1-3 and Comparative Examples 1-2 were placed in a constant temperature environment of 55°C for 48 hours, taken out, and after returning to room temperature, the pastes were observed for hardening, delamination, foaming, and changes in paste properties. The results are shown in the following table:

[0081] Table 2 Heat resistance test results

[0082]

[0083]

[0084] (3) Cold resistance test: The products of Examples 1-3 and Comparative Examples 1-2 were placed in a -15°C freezing environment for 24 hours, taken out, and after returning to room temperature, the ointments were observed for changes such as hardening, delamination, and precipitation. The results are shown in the following table:

[0085] Table 3 Cold resistance test results

[0086]

[0087] It can be seen from Table 1, Table 2 and Table 3 that Example 1 uses olive oil and refined lard in a ratio of 1:1 as a solvent, and then adds vaseline as an excipient. The ratio of olive oil to refined lard and vaseline is 1:1:3. The ointment obtained in Example 1, that is, the present invention, has no obvious separation of oil and water in the cold and heat resistance tests. The properties of the ointment are relatively more stable, with good homogeneity, and good moisturizing and skin penetration. Comparative Example 1 uses olive oil alone as a solvent and then adds vaseline as an excipient. Because olive oil is liquid, the ointment obtained after adding vaseline in proportion has a soft texture after forming and poor heat resistance, which is better than that in Example 1. The lack of refined lard weakens its moisturizing effect; Comparative Example 2 uses refined lard alone as a solvent, and the resulting lithospermum and sophora flavescens contents are the lowest among all groups; Example 2 uses olive oil: refined lard: vaseline in a ratio of 2:1:6, wherein olive oil and refined lard are used as solvents, and the moisturizing property is lower than that of Example 1, and in the cold resistance test of the ointment, a small amount of white granular precipitation can be seen in the paste, affecting the uniformity of the paste; Example 3 uses olive oil: refined lard: vaseline in a ratio of 1:2:3, wherein olive oil and refined lard are used as solvents, and in the cold resistance test of the obtained ointment, white granular precipitation can be seen in the paste, affecting the uniformity of the paste.

[0088] In summary, compared with Examples 2-3 and Comparative Examples 1-2, the ointment of Example 1 uses olive oil: refined lard: vaseline in a ratio of 1:1:3. There is no obvious separation of oil and water in both the cold resistance and heat resistance tests. The properties of the ointment are relatively more stable, the homogeneity is good, and the moisturizing and skin penetration properties are good.

[0089] 2. Toxicology Studies

[0090] The ointment obtained in Example 1 was subjected to animal experiments, as follows:

[0091] 1. Experimental Animals

[0092] Twenty healthy SPF-grade 6-week-old SD rats, half male and half female, weighing (170±10) g, were provided by Chengdu Dashuo Experimental Animal Co., Ltd. (SCXK (Sichuan) 2015-030) and housed in the Basic Medical Laboratory of the Western Theater Command General Hospital at a temperature of 20-25°C and a relative humidity of 50%-65%.

[0093] 2. Reagents and equipment

[0094] (1) Experimental equipment

[0095] The main experimental equipment is shown in the following table:

[0096] Table 4 Experimental equipment

[0097]

[0098] (2) Main experimental reagents

[0099] The main experimental reagents are shown in the following table:

[0100] Table 5 Experimental reagents

[0101]

[0102] 3. Experimental methods

[0103] (1) Experimental animal grouping

[0104] Using a combination group design, rats were arranged in ascending order of weight and divided into two combination groups of 10 males and 10 females. Four rows were randomly assigned using a random number table. Random numbers 1-5 were selected from each row and labeled sequentially under the rat numbers in each combination group. The random number under each rat number indicated the experimental group to which the rat was assigned.

[0105] Table 6 Experimental groups (weight unit: g)

[0106]

[0107] (2) Dosage design

[0108] To prevent skin irritation from the depilatory cream, this study used a small animal shaver to shave the rats' back hair (approximately 9 cm²). The shaved area was rinsed with sterile water and then dried with sterile gauze. The dosage of this Chinese herbal lip balm for human cheilitis is 0.2 g / cm² twice daily. Therefore, the rat group receiving a 2-fold dose received 0.4 g / cm² twice daily, while the rat group receiving a 5-fold dose received 1 g / cm² twice daily. Before each application, rinse with sterile water and gauze to remove any remaining ointment before reapplying.

[0109] (3) Animal handling and observation

[0110] Twenty rats were randomly divided into five groups according to the above method, with four rats in each group. The 2-fold 1-week group: the Chinese medicine lip balm was applied to the 1.5×1.5cm area in the center of the hair removal area, 2 times / day, 0.4g / cm2 each time, for 7 consecutive days; the 5-fold 1-week group: the Chinese medicine lip balm was applied to the 1.5×1.5cm area in the center of the hair removal area, 2 times / day, 1g / cm2 each time 2 , for 7 consecutive days; 2 times the dose for 2 weeks group: apply Chinese medicine lipstick on the 1.5×1.5cm area in the center of the hair removal area, 2 times / day, 0.4g / cm each time 2 , for 14 consecutive days; 5-fold dose 2-week group: Apply Chinese herbal lipstick to the 1.5×1.5cm area in the center of the hair removal area, 2 times / day, 1g / cm each time 2, for 14 consecutive days; normal group: no treatment, after external application, the rats' reactions were recorded in detail, the rats were observed for death and photographed, and finally, after the end of the experiment, the rats in each group were anesthetized by intraperitoneal injection of sodium pentobarbital (60 mg / kg). After opening the abdomen, the liver, kidney and skin tissue of each group of rats were quickly removed, the blood was rinsed with pre-cooled saline, and the rats were placed in 10% formaldehyde solution with a volume 10 times that of the liver, kidney and skin tissue of the external application for 24 hours for later use.

[0111] (4) Pathological observation of liver, kidney and skin tissues at the application site

[0112] The fixed liver, kidney and skin tissues at the application site were paraffin-dehydrated and 6 sections (4 μm) were randomly taken from each of the 4 rats in each group for routine hematoxylin-eosin (HE) staining. The morphological changes of the liver, kidney and skin tissues at the application site were observed under an ordinary light microscope (×100).

[0113] 4. Data collation and analysis

[0114] (1)Weight

[0115] In this study, the body weights of rats in each group were measured before the start of the experiment, one week after medication, and two weeks after medication. The rats were fasted overnight before each measurement, and the residual ointment was cleaned with sterile water and gauze. The results are shown in the following table:

[0116] Table 7 Body weight of rats in each group (unit: g)

[0117]

[0118] Note: The results are expressed as mean ± SD. There was no significant difference in body weight between the groups and the normal group (P>0.05) (n=4).

[0119] As shown in Table 7, there was no significant difference in body weight among the groups before the start of the experiment, one week after medication, and two weeks after medication (P>0.05), indicating that applying the Chinese herbal lipstick twice a day, 0.4g / cm2 or 1g / cm2 each time, for 7 or 14 days had no significant effect on the body weight of the rats, indicating that the drug does not affect the spleen and stomach function of the rats.

[0120] (2) Poisoning reactions and deaths

[0121] The poisoning reactions and deaths are shown in the following table:

[0122] Table 8 Toxic reactions and deaths of rats in each group

[0123]

[0124] As shown in Table 8, after the application of Chinese herbal lipstick, the rats in each group were observed for poisoning reactions and deaths. It was found that no vomiting, diarrhea, convulsions, coma or other poisoning reactions occurred in any group, and no deaths occurred. 2 or 1g / cm 2 External use of Chinese herbal lipstick will not cause poisoning or death after 7 or 14 days

[0125] (3) Skin condition

[0126] Figure 1 This is a rat skin image after external application of the ointment according to Example 1 of the present invention. Figure 1 (a) is the skin picture of rats in the normal group. Figure 1 (b) is the skin picture of rats in the 2-fold 1-week group. Figure 1 (c) is the skin picture of rats in the 2-fold 2-week group. Figure 1 (d) is the skin picture of rats in the 5-times 1-week group. Figure 1 (e) is the skin picture of rats in the 5-fold 2-week group. Figure 1 It can be seen that after applying 2 times and 5 times the dose of lithospermum ointment for 1 week or 2 weeks respectively, the skin of the rats in the drug-treated group was stained by the color of the lithospermum ointment itself, and there was no damage, swelling or other changes on the skin.

[0127] like Figure 1 As shown in the results, after each experiment, photographs of the rats' skin at the application site revealed that the rats that applied the herbal lipstick had their fur stained red by the lipstick, making it difficult to clean and resulting in a reddish appearance. However, the skin showed no damage, erosion, or swelling. This indicates that applying the herbal lipstick twice daily at 0.4g / cm² or 1g / cm² for 7 or 14 days did not cause skin damage, swelling, or erosion. Rats have abundant fur, and considering the irritation of depilatory creams, a small animal shaver was used. However, shaving with a small animal shaver often leaves hair follicle roots, which can easily stain the skin after application of the ointment and hinder skin cleaning. In human trials, the skin of the lips is smooth and not easily stained.

[0128] (4) Pathological staining results of liver, kidney and skin tissues at the application site

[0129] ① Tissue section preparation

[0130] After the external application experiment, HE staining was performed on the skin, liver, and kidney tissues of each group of rats. First, the corresponding tissue sections were prepared according to the experimental process of pathological tissue sampling, fixation, embedding, paraffin sectioning, and frozen sectioning.

[0131] ②Staining steps

[0132] Each section was stained according to the following procedure:

[0133] Dewax the paraffin sections to water: place the sections in environmentally friendly dewaxing solution I for 20 minutes, environmentally friendly dewaxing solution II for 20 minutes, anhydrous ethanol I for 5 minutes, anhydrous ethanol II for 5 minutes, and 75% alcohol for 5 minutes, and then wash with tap water.

[0134] Rewarming and fixation of frozen sections: Take the frozen sections out of the -20° refrigerator and restore them to room temperature. Fix them with tissue fixative for 15 minutes and then rinse with running water.

[0135] Hematoxylin staining: Stain the sections with hematoxylin solution for 3-5 minutes, wash with tap water, differentiate with differentiation solution, wash with tap water, blue with bluing solution, and rinse with running water.

[0136] Eosin staining: Dehydrate the sections in 85% and 95% graded alcohol for 5 minutes each, and then stain them in eosin solution for 5 minutes.

[0137] Dehydration and sealing: The sections were sequentially placed in anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, anhydrous ethanol III for 5 min, xylene I for 5 min, and xylene II for 5 min until transparent, and then sealed with neutral gum.

[0138] Microscopic examination, image acquisition and analysis, in which the cell nucleus appears blue and the cytoplasm appears red.

[0139] ③HE pathological staining results

[0140] The results of HE pathological staining were as follows Figure 2 、 Figure 3 、 Figure 4 As shown:

[0141] Figure 2 This is the HE staining picture of rat skin after external application of the ointment in Example 1, wherein: Figure 2 (a) HE staining of the skin of rats in the normal group. Figure 2 (b) HE staining of rat skin in the 2-fold 1-week group. Figure 2 (c) is the HE staining picture of the skin of rats in the 2-fold 2-week group. Figure 2 (d) is the HE staining picture of the rat skin in the 5-fold 1-week group. Figure 2 (e) is the HE staining picture of the rat skin in the 2-week group at 5 times the normal level. Figure 2It can be seen that compared with the normal group, the skin of the rats in the 2-fold 1-week group, the 2-fold 2-week group, the 5-fold 1-week group and the 5-fold 2-week group showed no other pathological changes except for the dilation of hair follicles. This may be because the excipients of the Chinese medicine ointment of the present invention are rich in oil, and long-term external application blocks the hair follicles, causing the dilation of hair follicles; while in the human trial, the Chinese medicine ointment was applied externally to the lips, and the lips are mucous membranes without hair follicles, so there is no need to worry about the impact on the hair follicles. In addition, the lips do not have accessory organs such as hair follicles, sebaceous glands and sweat glands, resulting in a lack of oil on the lip skin. The characteristic of this ointment being rich in oil is just suitable for use on the lip skin and does not cause obvious damage to the skin.

[0142] Figure 3 This is a HE staining image of rat liver after external application of the ointment in Example 1, wherein: Figure 3 (a) HE staining of the liver of rats in the normal group. Figure 3 (b) HE staining of the liver of rats in the 2-fold 1-week group. Figure 3 (c) HE staining of the liver of rats in the 2-week group. Figure 3 (d) HE staining of the liver of rats in the 5-fold 1-week group. Figure 3 (e) is the HE staining image of the liver of rats in the 2-week group at 5 times the normal level. Figure 3 The results showed that compared with the normal group, after external application of the ointment of the present invention, the hepatocytes of the rats in each group were neatly arranged and intact in morphology, with no enlarged nuclei. The hepatic lobules were intact in morphology, and no inflammatory cell infiltration, swelling, or necrosis was observed. This indicates that external application of the Chinese herbal lip balm at a dose of 0.4 g / cm² or 1 g / cm² twice a day for 7 or 14 days did not cause liver damage.

[0143] Figure 4 This is a HE staining image of rat kidney after external application of the ointment in Example 1, wherein: Figure 4 (a) HE staining of the kidney of rats in the normal group. Figure 4 (b) HE staining of the kidneys of rats in the 2-fold 1-week group. Figure 4 (c) HE staining of the kidneys of rats in the 2-fold 2-week group. Figure 4 (d) is the HE staining image of the kidney of rats in the 5-fold 1-week group. Figure 4 (e) is the HE staining image of the kidney of rats in the 5-fold 2-week group. Figure 4 Compared with the normal control group, the glomerular morphology of rats in all groups was normal, with no edema, granular degeneration, interstitial inflammatory cell infiltration, or hemorrhage in the renal tubular epithelium. This suggests that applying the Chinese herbal lip balm twice daily at a dose of 0.4 g / cm² or 1 g / cm² for 7 or 14 days does not cause kidney damage.

[0144] Depend on Figure 2 、 Figure 3 and Figure 4 It can be seen that the ointment of the present invention is very safe.

[0145] 3. Clinical Trial Cases

[0146] The inventors conducted a follow-up trial on 20 patients using this ointment for the prevention and treatment of cheilitis. These patients applied a thin layer of the ointment to their lips using a cotton swab or clean fingertips, once each after breakfast and lunch, and before bedtime, or once each morning and evening. Almost all patients reported significant efficacy of the ointment in treating cheilitis. Typical cases are listed below:

[0147] Case 1: A 26-year-old female patient presented with recurrent chapped lips for over 10 years.

[0148] Medical history: The patient complained that she had felt that her lips were often dry since she was in junior high and high school, and sometimes her lips would crack when she laughed. At first, she did not know it was cheilitis, so she applied sesame oil and took vitamin supplements. After entering college, she applied lip balm. However, her lips only felt normal in the morning after brushing her teeth and washing her face, and then they would become very dry. She also used tacrolimus ointment, which she applied every night. It would be fine during the day, but she could not stop using it. If she stopped, it would relapse. If she applied lipstick during the day, the cheilitis would be more serious the next day.

[0149] Treatment: Use a cotton swab or clean fingertips to dip the ointment and apply a thin layer on the lips, once after breakfast, lunch and before bed.

[0150] Results: After 5 days of treatment, the chapped lips were significantly improved, and there was no recurrence after 1 month of intermittent use. Figure 5 This is a graph showing the changes in Case 1 before and after treatment.

[0151] Case 2: A 30-year-old female patient presented with dry lips for more than 10 days.

[0152] Medical history: The patient complained that he suddenly felt dry and painful lips more than 10 days ago and liked to lick his lips.

[0153] Treatment: Use a cotton swab or clean fingertips to dip the ointment and apply a thin layer on the lips, once after breakfast and before bedtime.

[0154] Results: The pain was relieved after 1 day of treatment, and it started to heal after 2 days of use. I applied the medicine once on the 4th day, and did not apply the medicine again on the 5th day. It was completely healed on the morning of the 6th day. Figure 6 This is the change diagram of Case 2 before and after treatment.

[0155] Case 3: A 26-year-old male presented with recurrent dry lips and scabs for over 5 years.

[0156] Medical History: The patient complained of recurrent chapped lips for over five years. Five years ago, the condition was less severe, initially characterized by a tendency to lick her lips. Around 2019, the condition became more severe, becoming extremely uncomfortable without daily lipstick application. She visited local hospitals multiple times, with no success, and was prescribed various medications. In severe cases, her lips became dry and chapped, with frequent cracks and bleeding around the lips that required scabs to heal. When washing, her lips would turn white upon contact with water, and the chapped lips would recur repeatedly. She also experienced discomfort in her tongue and itchy lips, which affected her mood and made her extremely irritable. In the past, applying lipstick or other medications would cause her lips to become crusty and chapped.

[0157] Treatment: Use a cotton swab or clean fingertips to dip the ointment and apply a thin layer on the lips, once after breakfast, lunch and before bed.

[0158] Results: After 2 days of treatment, the dryness and scabs were relieved, and after 4 days of use, they were basically healed, but there was still a little peeling. Figure 7 This is the change diagram of Case 3 before and after treatment.

[0159] Case 4: A 28-year-old male presented with recurrent dry lips and scabs for over 8 years.

[0160] Medical History: The patient reported experiencing dry lips since high school. The skin peeled off and then started flaking again, with dryness and scabbing forming over the course of the illness. Even after graduating from college and now working for four years, the condition continued to recur. During this time, the patient took traditional Chinese medicine intermittently and visited a tertiary hospital, where they were treated for cheilitis, but all were ineffective.

[0161] Treatment: Use a cotton swab or clean fingertips to dip the ointment and apply a thin layer on the lips, once after breakfast, lunch and before bed.

[0162] Results: After one week of treatment, the condition improved significantly, the chapped lips were significantly improved, and there was no bleeding or scab. Figure 8 This is a graph showing the changes in Case 4 before and after treatment.

[0163] Case 5: A 32-year-old female presented with recurrent herpes labialis and scabs for over 2 years.

[0164] Medical History: The patient reported recurring herpes around the lips, primarily on the upper lip, starting two years ago. Hard scabs typically appeared two to three days after the rash, accompanied by pain, dryness, and bleeding. The rash was more likely to flare up when the patient was sleep deprived. While the condition improved with topical medications, the scabs fell off and became prone to bleeding during treatment.

[0165] Treatment: Use a cotton swab or clean fingertips to dip the ointment and apply a thin layer on the lips, once after breakfast, lunch and before bed.

[0166] Results: After 5 days of treatment, the scabs fell off naturally without bleeding and pain. The lips felt moisturized. Figure 9This is a graph showing the changes in Case 5 before and after treatment.

[0167] In summary, the ointment of the present invention has a high content of active medicinal ingredients, stable properties, good homogeneity, strong moisture retention and skin penetration. The ointment can form a stable protective drug oil film on the surface of the lip skin, enhance the antioxidant capacity of skin cells, and at the same time reduce water volatilization, providing nutrition and essential amino acids and trace elements for the skin surface cells; the drug ingredients contained in the composition achieve local anti-inflammatory, antibacterial and antioxidant effects, and improve microcirculation by promoting blood circulation and removing blood stasis, thereby promoting tissue regeneration and repair; the present invention can not only effectively treat dry and chapped lip skin, but also further improve the antioxidant capacity of local skin, achieving prevention and treatment in one.

[0168] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A composition for preventing and treating cheilitis, characterized in that: It is composed of the following raw materials: 25 parts by weight of Sophora flavescens, 15 parts by weight of Lithospermum officinale, 1 part by weight of Sichuan pepper, 100 parts by volume of olive oil, 100 parts by volume of animal fat, and 300 parts by volume of vaseline, wherein, when the weight unit is g, the volume unit is mL; The animal fat is refined lard; The composition is in the form of an ointment, and its preparation method comprises the following steps: 1) Pour olive oil and animal fat into a container and heat, maintaining the oil temperature at 60-80°C until the animal fat is completely melted to obtain a mixed oil; 2) Add Sophora flavescens to the mixed oil obtained in step 1), heat until the oil bubbles, maintain this temperature for about 20 minutes, or until the Sophora flavescens is completely browned, filter and remove the residue to obtain medicinal oil A; 3) When medicinal oil A cools to 70-80°C, add Sichuan peppercorns and maintain the oil temperature at 70-80°C until the surface of the peppercorns turns black. Filter to remove the residue to obtain medicinal oil B. 4) Cool the medicinal oil B obtained in step 3) to 55-60°C, add the lithospermum erythrorhizon, control the bubbling of the medicinal oil B, and continue stirring until the lithospermum erythrorhizon is completely submerged in the oil. Turn off the heat, let it stand for 3-7 days to fully extract the medicinal drug, and filter to remove the residue to obtain medicinal oil C; 5) Heat the medicinal oil C obtained in step 4), add petroleum jelly, maintain the temperature not higher than 80°C, and stir until the petroleum jelly and medicinal oil C are completely blended. Then, divide the mixture into containers and refrigerate to obtain an ointment.

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