Pharmaceutical composition with effect of treating acne

Abstract

The invention discloses a pharmaceutical composition with an effect of treating acne. The pharmaceutical composition comprises the following raw material medicines in parts by weight: 45-80 parts of citrus chachiensis hortorum, 12-32 parts of glabrous sarcandra herb and 5-9 parts of morinda citrifolia. The pharmaceutical composition disclosed by the invention has an obvious improvement effect on skin lesion of rat auricle acne induced by propionibacterium acnes, can inhibit proliferation of the propionibacterium acnes, and can be used for treating diseases related to skin appendages. The skin appendage related diseases comprise acne, folliculitis, seborrheic dermatitis and androgenetic alopecia.

Description

Technical Field

[0001] The invention belongs to the field of medicine, and in particular relates to a pharmaceutical composition for treating acne. Background Art

[0002] Acne is the most common inflammatory skin disease in the world, and it is prone to occur on the face, neck, chest, shoulder blades, and other areas of the human body rich in hair follicles and sebaceous glands. At the same time, severe acne can have a significant impact on a person's appearance and mental health. The pathogenesis of acne is relatively complex, mainly including excessive secretion of sebum by sebaceous glands, excessive keratinization of hair follicle sebaceous gland units, androgen effects, and abnormal proliferation of Propionibacterium acnes. At present, the topical use of topical medications with anti-inflammatory, bactericidal, antipruritic, and degreasing effects is considered to be the first-line treatment option. Clinically, acne is often treated with topical or oral retinoic acid or antibiotics. However, retinoic acid has certain side effects, and many patients experience dry skin, desquamation, and even worsening skin lesions. In addition, acne often recurs, and long-term use of antibiotics will promote the development of drug resistance in Propionibacterium acnes and may cause an imbalance in the flora structure of the epidermis.

[0003] Traditional Chinese medicine not only has extensive clinical experience in the prevention and treatment of acne, but also has outstanding efficacy. It can effectively relieve and eliminate patients' clinical symptoms, improve skin quality, and has significant advantages in preventing recurrence. For example, Chinese invention patent application 118767030A discloses a Chinese medicinal ointment for treating acne caused by internal dampness, wherein the composition of the Chinese medicinal ointment is: 10-20 parts of Scutellaria baicalensis, 20-40 parts of Astragalus membranaceus, 15-30 parts of Centella asiatica, 20-30 parts of Bletilla striata, 20-50 parts of Salvia miltiorrhiza and 20-40 parts of Coix seeds; Chinese invention patent application 118767030A discloses a Chinese medicinal combination with anti-inflammatory, analgesic and antipruritic effects, as well as a preparation method and application thereof, wherein the Chinese medicinal combination is: 330-500 parts of Rehmannia root, 330-500 parts of processed Polygonum multiflorum, 200-300 parts of Saposhnikovia divaricata, 270-400 parts of Morus alba, 130-200 parts of Periostracum Cicadae, 270-400 parts of Sophora flavescens, 270-400 parts of Anemarrhena asphodeloides and 270-400 parts of Cortex Lycii. However, the therapeutic effect of the drugs in the above patent documents on acne needs to be further improved.

[0004] Therefore, there is an urgent need to develop a Chinese medicine composition for treating acne that is highly safe, simple in medicine, and more effective. Summary of the invention

[0005] The onset of acne is mostly caused by deficiency of Yin in the body and heat in the blood, and phlegm and dampness are accumulated on the skin surface, which turns into heat and causes lung wind acne. In view of the existing diagnosis and treatment system of acne, the present invention provides a Chinese medicine composition for treating acne composed of Guang Chenpi, Radix Salviae Miltiorrhizae, and Noni fruit. In the Chinese medicine composition of the present invention, Guang Chenpi dries dampness and resolves phlegm, and can be used for all symptoms of qi stagnation, dampness obstruction, and phlegm congestion, and can cleanse the phlegm and dampness congestion in the skin. Guang Chenpi is an authentic raw material from the production area (Xinhui, Guangdong) among the Chinese medicine tangerine peel, and has the best quality among tangerine peels. Radix Salviae Miltiorrhizae clears heat and cools blood, can eliminate the stagnant heat on the skin surface, and has the function of promoting blood circulation and eliminating spots, helping the epidermis to clear rashes and remove spots. Noni fruit can clear heat and relieve pain to treat the symptoms, and nourish yin and produce body fluid to treat the root cause. All the medicines are used together to play the functions of clearing heat, cooling blood, eliminating spots, removing dampness, nourishing yin and regulating qi. According to the results of pharmacological experiments and in vitro experiments, the important composition of the present invention has anti-inflammatory, bactericidal and fat-removing effects, is highly safe, simple in medicine and effective, and is suitable for treating acne.

[0006] The technical solution of the present invention to solve the above problems is as follows:

[0007] A pharmaceutical composition with the effect of treating acne, the pharmaceutical composition is composed of a traditional Chinese medicine extract and medically acceptable auxiliary materials, the raw materials used are all common commercially available products, and their sources are not specifically limited. The pharmaceutical composition comprises the following components by weight: 45-80 parts of dried orange peel, 12-32 parts of Sarcandra chinensis, and 5-9 parts of noni fruit.

[0008] In the above scheme, the optimal ratio of the raw materials is: 63 parts of dried orange peel, 32 parts of Sarcandra chinensis, and 9 parts of Noni fruit.

[0009] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition having the effect of treating acne, comprising the following steps:

[0010] The raw material medicine is taken, dried and crushed, extracted with ethanol or ethanol aqueous solution, filtered to obtain an extract, and the extract is freeze-dried after removing ethanol to obtain a pharmaceutical composition.

[0011] Preferably, the ethanol aqueous solution is an ethanol aqueous solution with a volume fraction of 75%, and 10 times the amount of the raw material drug is added for leaching.

[0012] Preferably, the extraction is performed by adding 10 times the volume fraction of 75% ethanol aqueous solution, ultrasonic extraction is performed 3 times, each time for 5-25 minutes, and then sealing and soaking in a dark place for 14-21 days.

[0013] Preferably, the filtration obtains an extract, the extract is filtered through a 0.22 μm filter membrane, the liquid is collected, ethanol is evaporated, and then freeze-dried to obtain a pharmaceutical composition.

[0014] The drug combination of the present invention is a common external preparation, such as an aqueous solution, an ointment, an emulsion, a tincture or a gel.

[0015] The present invention also provides application of the above-mentioned pharmaceutical composition in preparing a drug for treating acne.

[0016] The pharmaceutical composition of the present invention has a significant improvement effect on the acne lesions of rat auricle induced by Propionibacterium acnes, can inhibit the proliferation of Propionibacterium acnes, and can be used for the treatment of skin appendage-related diseases. The skin appendage-related diseases include: acne, folliculitis, seborrheic dermatitis and androgenic alopecia. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 Response surface diagram and contour diagram of the interaction effect of three factors on the minimum inhibitory concentration. DETAILED DESCRIPTION

[0018] The present invention is described in detail below in conjunction with specific embodiments.

[0019] Guang Chenpi: Dried mature peel of Citrus reticulata 'Chachi', a plant of Rutaceae. Take the original medicinal material, remove impurities, spray with water, moisten thoroughly, cut into strips, and dry in the shade.

[0020] Sarcandra glabra: The dried whole herb of Sarcandra glabra (Thunb.) Nakai, a plant of the family Sarcandiaceae. Take the original herb, remove impurities, wash, moisten thoroughly, cut into sections, and dry.

[0021] Noni fruit: The fruit of Morinda citrifolia L. Take the original medicinal material, remove impurities, and dry it.

[0022] Example 1

[0023] This embodiment provides a Box-Behnken response surface optimization test of the pharmaceutical composition with the effect of treating acne. The three factors of the addition amount of Guang Chenpi, the addition amount of Zhongjiefeng and the addition amount of Noni fruit were selected as independent variables, and a 3-factor 3-level test was designed using Box-Behnken. The experimental factors and levels are detailed in Table 1. Take the raw material medicine according to the addition amount in Table 1, dry and crush it, add 10 times the amount of 75% alcohol, ultrasonically extract it 3 times, each time for 20 minutes, and then seal it in a dark place to soak for 21 days; remove the residue and collect the extract, pass the obtained drug solution through a 0.22μm filter membrane, collect the liquid, evaporate the ethanol by rotary evaporation, and freeze-dry to obtain freeze-dried powder. The minimum inhibitory concentration (Propionibacterium acnes) of each extract freeze-dried powder was determined by the microbroth dilution method (Ksouda G, Sellimi S, Merlier F, et al. Composition, antibacterial and antioxidant activities of Pimpinella saxifraga essential oil and application to cheese preservation as coating additive [J]. Food Chemistry, 2019, 288: 47-56), and the drug addition amount was optimized with the minimum inhibitory concentration as the response value. The response surface design experiment and results are shown in Table 2.

[0024] Table 1 Response surface experimental factors and levels

[0025]

[0026] Table 2 Response surface design experiment and minimum inhibitory concentration results

[0027]

[0028]

[0029] The variance analysis of the minimum inhibitory concentration results was performed using Design-Expert software, and the quadratic polynomial regression equation model of A (amount of added tangerine peel), B (amount of added scutellaria baicalensis), and C (amount of added noni fruit) was obtained as follows:

[0030] Minimum inhibitory concentration = 0.29-0.028A-0.024B-0.0025C-0.00975AB+0.005AC+0.006BC+0.047A 2 +0.034B 2 +0.016C 2

[0031] The variance analysis of the regression model is shown in Table 3.

[0032] Table 3 Analysis of variance of regression model

[0033] Sources of variance sum of squares Degrees of Freedom Mean Square F-number P-value Model 0.0283 9 0.003140898 35.4932343 <0.0001 A 0.0061 1 0.006105125 68.99003148 <0.0001 B 0.004656 1 0.004656125 52.61582856 0.0002 C 0.00005 1 0.00005 0.565017354 0.4768 AB 0.00038025 1 0.00038025 4.296956978 0.0769 AC 0.0001 1 0.0001 1.130034708 0.3231 BC 0.000144 1 0.000144 1.62724998 0.2428 A^2 0.00927139 1 0.009271392 104.7699487 <0.0001 B^2 0.0049898 1 0.0049898 56.38662056 0.0001 C^2 0.0011016 1 0.001101603 12.44849208 0.0096 Residual 0.00061945 7 8.84929E-05 Proposed Loss 0.00045225 3 0.00015075 3.60645933 0.1236 Pure Error 0.0001672 4 0.0000418 sum 0.0288875 16

[0034] As shown in Table 3, the regression equation model P < 0.0001 is extremely significant, the lack of fit term is not significant (P = 0.1236 > 0.05), and the model R 2 =0.9786, indicating that the model has a good degree of fit and a high correlation between the actual value and the predicted value. Therefore, the model can better reflect the influence of each factor on the response value and predict the optimal addition ratio. From the P value, it can be seen that the addition amount of Guang Chenpi A, the addition amount of Sargassum sarmentosum B, the interaction term AB and each quadratic term are extremely significant (P<0.01), the interaction term AB is significant (P<0.05), and the others are not significant. From the F value, it can be seen that the influence order of the three main factors is: A>B>C, that is, the addition amount of Guang Chenpi>the addition amount of Sargassum sarmentosum>the addition amount of Noni fruit.

[0035] The quadratic polynomial regression equation given by Design-Expert software was used to draw a response surface diagram of the interaction between various factors on the minimum inhibitory concentration ( Figure 1 ). The color change in the contour map indicates the change in the response value. The faster the color change and the denser the contour lines, the greater the slope, that is, the more significant the impact on the minimum inhibitory concentration. At the same time, the shape of the contour lines also reflects the strength of the interaction between the factors. An ellipse indicates that the interaction between the research factors is significant. Figure 1 The results showed that the amount of dried orange peel added and the amount of Radix Sarcosaefolia added had a significant interaction. The optimal drug formula for antibacterial effect was obtained by response surface equation calculation, but considering the actual operation, the optimal ratio was: 63 parts of dried orange peel, 32 parts of Radix Sarcosaefolia, and 9 parts of Noni fruit.

[0036] Example 2

[0037] The invention discloses a method for preparing 63 parts of dried orange peel, 32 parts of scutellaria baicalensis and 9 parts of noni fruit by weight, and then drying and crushing them, adding 10 times the amount of 75% alcohol, and ultrasonically extracting them for 3 times, each time for 20 minutes, and then sealing them and soaking them in a dark place for 21 days; removing the residue and collecting the extract, filtering the obtained medicinal solution through a 0.22 μm filter membrane, collecting the liquid, evaporating the ethanol by rotary evaporation, and freeze-drying the liquid to obtain a freeze-dried powder.

[0038] Example 3

[0039] According to the mass ratio, 45 parts of dried orange peel, 30 parts of Sarcandra scutellariae, and 5 parts of Noni fruit are taken, dried and crushed, and then 10 times the amount of 75% alcohol is added, and ultrasonic extraction is performed for 3 times, each time for 20 minutes, and then the mixture is sealed and soaked in a dark place for 21 days; the residue is removed and the extract is collected, and the obtained medicinal solution is filtered through a 0.22 μm filter membrane, and the liquid is collected, the ethanol is evaporated, and then freeze-dried to obtain freeze-dried powder.

[0040] Example 4

[0041] The invention discloses a method for preparing 80 parts of dried orange peel, 12 parts of scutellaria baicalensis and 8 parts of noni fruit by weight, and then drying and crushing them, adding 10 times the amount of 75% alcohol, and ultrasonically extracting them for 3 times, each time for 20 minutes, and then sealing them and soaking them in a dark place for 21 days; removing the residue and collecting the extract, filtering the obtained medicinal solution through a 0.22 μm filter membrane, collecting the liquid, evaporating the ethanol by rotary evaporation and freeze-drying to obtain freeze-dried powder.

[0042] Example 5

[0043] Take 500 grams of dried tangerine peel, dry and crush it, add 10 times the amount of 75% alcohol, ultrasonically extract it 3 times, each time for 20 minutes, and then seal it and soak it in a dark place for 21 days; remove the residue and collect the extract, pass the obtained medicinal solution through a 0.22μm filter membrane, collect the liquid, evaporate the ethanol, and freeze-dry it to obtain freeze-dried powder.

[0044] Example 6

[0045] Take 500 grams of Radix Achyranthis Bidentatae, dry and crush it, add 10 times the amount of 75% alcohol, perform ultrasonic extraction for 3 times, each time for 20 minutes, and then seal it and soak it in a dark place for 21 days; remove the residue and collect the extract, filter the obtained medicinal solution through a 0.22μm filter membrane, collect the liquid, evaporate the ethanol by rotary evaporation, and freeze-dry it to obtain freeze-dried powder.

[0046] Example 7

[0047] Take 500 grams of noni fruit, dry and crush it, add 10 times the amount of 75% alcohol, perform ultrasonic extraction 3 times, each time for 20 minutes, and then seal it and soak it in a dark place for 21 days; remove the residue and collect the extract, pass the obtained liquid through a 0.22μm filter membrane, collect the liquid, evaporate the ethanol, and freeze-dry it to obtain freeze-dried powder.

[0048] Example 8 (Efficacy Experiment)

[0049] Reagents and samples: Sterilize vaseline, and fully stir the sterilized vaseline and the freeze-dried powder of the Chinese herbal extract in Example 2-7 at a mass ratio of 10:1 for 90-120 minutes until the paste is uniform, thereby obtaining the ointment of Example 2-7.

[0050] Experimental animals and modeling: SD rats weighing 200±20g, male, were selected. 200μL oleic acid was applied to the opening of the right auricle duct twice a day, with an interval of more than 8h between the two applications. 100μL Propionibacterium acnes suspension (6×10 7 CFU / mL) for 14 consecutive days. The rats' auricles showed obvious thickening, redness and swelling of the epidermis, and hardening of the texture, indicating that the model was successfully established.

[0051] Animal administration: 80 rats with successful modeling were selected and then divided into a model group, a vaseline group, and an embodiment 2-7 group, with 10 rats in each group. Ten healthy SD rats were taken as a blank control group. The embodiment 2-7 group was given the corresponding ointment, with a dosage of 11.6g crude drug / kg and a coating thickness of 0.1-0.2cm. Once a day. The vaseline group was given 2.32g vaseline applied to the lesions once a day. The model group was given 200ul of normal saline applied to the lesions once a day for 14 consecutive days.

[0052] The rats in each group were dissected and sampled the next day after the last administration. They were required to fast for 24 hours before sampling. 10% chloral hydrate (prepared with saline) was injected intraperitoneally to anesthetize the rats. The thickness of the right auricle of each rat was measured with a vernier caliper and recorded as the auricle thickness value after treatment. The erythema index of the test skin was measured using the Skin Color function of the skin detector to index the degree of inflammatory reaction (the erythema value reflects the redness and swelling of the skin and can determine whether there is inflammation). After opening the abdomen, 3-5 ml of blood was collected from the abdominal aorta, and it was left to stand at 4°C overnight (more than 12 hours). After stratification, the supernatant was aspirated, and the TNF-α and T levels in the rat serum were detected by enzyme-linked immunosorbent assay. The results are shown in Table 4-5.

[0053] Table 4 Effect of the Chinese medicine composition of the present invention on the auricle thickness and erythema index of rats

[0054]

[0055]

[0056] Compared with the model group: *P<0.05, the difference is significant; compared with the Example 2 group: #P<0.05, the difference is significant.

[0057] As shown in Table 4, after Propionibacterium acnes modeling, the auricle thickness and erythema values ​​of rats increased significantly (P<0.05), while Examples 2 to 7 groups were able to significantly reduce the auricle thickness and erythema values ​​of rats, and the effect of Example 2 group was significantly better than that of other Example groups, and the difference was significant (P<0.05).

[0058] Table 5 Effect of the Chinese medicine composition of the present invention on TNF-α and T levels in rat serum

[0059] Group TNF-α(pg / ml) T(pg / ml) Blank control group 47.5±10.5* 17.654±1.061* Model Group <![CDATA[147.4±21.7 # ]]> <![CDATA[23.983±0.851 # ]]> Vaseline control group <![CDATA[139.1±19.7 # ]]> <![CDATA[23.051±0.912 # ]]> Example 2 Group 61.3±10.1* 17.776±1.106* Example 3 Group <![CDATA[89.1±14.1 # *]]> <![CDATA[18.912±0.957 # *]]> Example 4 Group <![CDATA[85.1±13.6 # *]]> <![CDATA[19.921±0.993 # *]]> Example 5 Group <![CDATA[90.1±12.4 # *]]> <![CDATA[19.205±0.829 # *]]> Example 6 Group <![CDATA[101.3±13.1 # *]]> <![CDATA[20.741±1.112 # *]]> Example 7 Group <![CDATA[110.0±9.5 # *]]> <![CDATA[21.507±0.798 # *]]>

[0060] Compared with the model group: *P<0.05, the difference is significant; compared with the Example 2 group: #P<0.05, the difference is significant.

[0061] As shown in Table 5, after Propionibacterium acnes modeling, the TNF-α and T levels in the rat serum increased significantly (P<0.05), while Examples 2 to 7 groups were able to significantly reduce the TNF-α and T levels in the rat serum, and the effect of Example 2 group was better than that of the other Example groups, and the difference was significant (P<0.05).

Claims

1. A pharmaceutical composition for treating acne, characterized in that: The raw materials of the pharmaceutical composition include the following components by weight: 45-80 parts of dried orange peel, 12-32 parts of Sarcandra scabra, and 5-9 parts of Morinda officinalis.

2. The pharmaceutical composition according to claim 1, characterized in that The raw materials are calculated by mass as follows: 63 parts of dried orange peel, 32 parts of Sarcandra scutellariae, and 9 parts of Noni fruit.

3. A method for preparing the pharmaceutical composition for treating acne according to claim 1, characterized in that: The following steps are involved: The raw material medicine is taken, dried and crushed, extracted with ethanol or ethanol aqueous solution, filtered to obtain an extract, and the extract is freeze-dried after removing ethanol to obtain a pharmaceutical composition.

4. The preparation method according to claim 3, characterized in that: The ethanol aqueous solution is an ethanol aqueous solution with a volume fraction of 75%, and 10 times the amount of the raw material drug is added for leaching.

5. The preparation method according to claim 3, characterized in that: The extraction is performed by adding 10 times the volume fraction of 75% ethanol aqueous solution, ultrasonic extraction for 3 times, each time for 5-25 minutes, and then sealing and soaking in a dark place for 14-21 days.

6. The preparation method according to claim 3, characterized in that: The filtration obtains an extract, and the extract is filtered through a 0.22 μm filter membrane, and the liquid is collected, ethanol is evaporated, and then freeze-dried to obtain a pharmaceutical composition.

7. Use of the pharmaceutical composition according to claim 1 in the preparation of a drug for treating acne.

8. The use according to claim 7, characterized in that: The pharmaceutical composition is an aqueous solution, an ointment, an emulsion, a tincture or a gel.

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