Anti-hair loss composition containing metronidazole and preparation method thereof

Abstract

The invention discloses a preparation method of an anti-hair loss composition containing metronidazole. A production raw material formula comprises minoxidil, a regulator and pharmaceutically acceptable auxiliary materials, the mass ratio of minoxidil to the conditioning agent is 1: (0.1-0.4); the regulator comprises metronidazole. The minoxidil-containing anti-alopecia composition has the advantage that the inhibition effect of the minoxidil-containing anti-alopecia composition on scalp grease secretion of a seborrheic alopecia patient can be remarkably enhanced.

Description

Technical Field

[0001] The invention relates to the field of medical technology, in particular to a production technology of an anti-hair loss composition. Background Art

[0002] Hair is a barometer of human health. A healthy body will naturally have shiny and lustrous hair because of adequate nutrition. When the body is not in good health, the hair will become dull and lose its luster, and even break and fall off. In recent years, with the continuous improvement of living standards, more and more people have begun to realize the importance of personal image. Hair, which occupies a commanding position in the overall image, cannot be ignored. As an important part of human beauty, hair shoulders the important task of showing the beautiful overall image of human beings.

[0003] Hair loss refers to the symptom of at least 100 hairs falling out every day, a decrease in the early growth phase, and an increase in the mid-growth and telogen phases. As hair loss progresses, the hair rate in the telogen phase increases rapidly, and the hair rate in the early growth phase decreases accordingly. Hair loss can generally include hereditary androgenic alopecia (baldness), alopecia areata, tinea capitis caused by fungal infection, telogen effluvium, trichotillomania, hair growth disorders, etc. The most common hair loss includes baldness (male pattern baldness), female pattern baldness, alopecia areata, and telogen effluvium. Modern pathological studies have shown that the causes of hair loss include endocrine disorders, long-term mental tension and stress, malnutrition, long-term hair dyeing and perming, etc.

[0004] At present, common hair loss treatment products include finasteride and minoxidil. The composition containing minoxidil, as an external medicine, can dilate scalp blood vessels, increase blood flow to hair follicles, improve the nutrient supply to hair follicles, and thus help hair growth. At the same time, it can also prolong the hair growth period, increase the thickness and length of hair, and has a certain effect in the treatment of seborrheic alopecia.

[0005] However, since the minoxidil-containing compositions currently on the market are not specifically for seborrheic alopecia, their effect on improving the oil secretion of the patient's scalp when used alone is very limited. In addition, glycerin and other solvents are often used, and patients often experience discomfort due to greasy scalp during use. It is usually necessary to use other treatment methods such as anti-lipid drugs at the same time, which increases the treatment cost and is not convenient for patients.

[0006] Therefore, how to enhance the inhibitory effect of the anti-hair loss composition containing minoxidil on the scalp oil secretion of patients with seborrheic alopecia is a technical problem to be solved in the art. Summary of the invention

[0007] In order to enhance the inhibitory effect of a minoxidil-containing anti-hair loss composition on scalp oil secretion of patients with seborrheic alopecia, the present invention provides an anti-hair loss composition containing metronidazole and a preparation method thereof.

[0008] The technical scheme adopted by the present invention is: a preparation method of an anti-hair loss composition containing metronidazole, wherein the production raw material formula comprises minoxidil, a regulator and pharmaceutically acceptable excipients; the mass ratio of the minoxidil to the regulator is 1:0.1-0.4; and the regulator comprises metronidazole.

[0009] As a further improvement of the present invention, the production raw material formula also includes a composite inhibitor, and the mass ratio of metronidazole to the composite inhibitor is 1:1.5-4.5. Wherein, the composite inhibitor includes a Sophora japonica flower extract.

[0010] The Sophora japonica extract of the present invention can be prepared according to the following method:

[0011] S1, soaking Sophora japonica flowers in water, adding acetic acid bacteria, and cultivating at 25-33°C for 2-5 days to obtain a mother solution; the mass ratio of acetic acid bacteria to Sophora japonica flowers is 1:5×10 5 ~2×10 6 ;

[0012] S2, heating the mother liquor to 93-96° C., recovering the generated steam to obtain a reflux liquid;

[0013] S3, concentrating and drying the reflux liquid at 85-92° C. until the water content is less than 5%, thereby obtaining the product.

[0014] As a further improvement of the present invention, the composite inhibitor is composed of Sophora japonica flower extract and South African leaf dry powder in a mass ratio of 1:0.2-1.

[0015] The South African leaf dry powder of the present invention can be prepared according to the following method:

[0016] A. Wash and crush the South African leaves and put them into a sealable container, add a saturated ammonium chloride solution, the mass of which is 1% to 3% of the mass of the South African leaves, mix well, seal the container, and let it stand at room temperature for 7 to 15 days to obtain a mixture;

[0017] B. freeze-drying the mixture at -12 to -35°C until the moisture content is less than 3% to obtain a freeze-dried material;

[0018] C. Grind the freeze-dried material into powder.

[0019] It is easy to understand that the pharmaceutically acceptable excipients of the present invention include anti-adsorbents, pH buffers, stabilizers and viscosity enhancers; such a solution is convenient for making the composition into an ointment for application, and in addition, it can also be used as a spray after being combined with auxiliary materials such as cosolvents and moisturizers.

[0020] For example, the anti-adsorption agent, pH buffer, stabilizer and thickener can be selected from the following components in the following mass proportions: 1 part of polysorbate, 0.6-1.5 parts of glycine, 2-4 parts of trehalose, and 0.01-0.1 parts of sodium hyaluronate.

[0021] The preparation method of the present invention only needs to mix the above raw materials with appropriate solvents such as glycerol and mix them evenly. The mass percentage content of minoxidil in the composition can be controlled to 1% to 8% by adjusting the amount of solvent and auxiliary materials added to ensure the therapeutic effect. It is easy to understand that the ratio of solvent and auxiliary materials needs to be appropriate to ensure that the fluidity of the ointment is moderate, which will not be repeated here.

[0022] The invention also discloses an anti-hair loss composition containing metronidazole, which is prepared by the preparation method of the anti-hair loss composition containing metronidazole of the invention.

[0023] The invention has the beneficial effect of significantly enhancing the inhibitory effect of the anti-hair loss composition containing minoxidil on the scalp oil secretion of patients with seborrheic alopecia. DETAILED DESCRIPTION

[0024] The present invention is further described below in conjunction with embodiments.

[0025] Raw material preparation:

[0026] The following raw materials used in the following examples and comparative examples were prepared according to the following steps, and the same batch of raw materials were used to reduce errors.

[0027] Sophora japonica flower extract:

[0028] (1) Soak the Sophora japonica flowers in a solvent and add acetic acid bacteria to Sophora japonica flowers at a mass ratio of 1:1×10 6 Add acetic acid bacteria in a ratio of , and cultivate at 31°C for 3 days to obtain mother solution;

[0029] (2) heating the mother liquor to 94° C., recovering the generated steam, and obtaining a reflux liquid;

[0030] (3) The reflux liquid was concentrated and dried at 89° C. until the water content was 3.7%, thereby obtaining a Sophora japonica flower extract.

[0031] South African leaf powder:

[0032] (1) Wash and crush the South African leaves and put them into a sealed container, add a saturated ammonium chloride solution, the mass of the saturated ammonium chloride solution added is 2.5% of the mass of the South African leaves, mix well, seal the container, and let it stand at room temperature for 14 days to obtain a mixture;

[0033] (2) freeze-drying the mixture at -18°C until the moisture content is 2.4% to obtain a freeze-dried material;

[0034] (3) Grinding the freeze-dried material into fine powder to obtain South African leaf dry powder.

[0035] Embodiment 1:

[0036] The anti-hair loss composition was prepared as follows:

[0037] (1) Measure the raw materials according to the following mass ratio: 1 part of minoxidil and 0.3 part of the regulator (metronidazole);

[0038] (2) Measure the excipients according to the following mass ratio: 1 part of polysorbate, 1.2 parts of glycine, 2.4 parts of trehalose, and 0.04 parts of sodium hyaluronate;

[0039] (3) mixing the auxiliary material and the solvent glycerol in a mass ratio of 1:0.4 to obtain a buffer system;

[0040] (4) adding the buffer system to the raw materials and mixing them evenly, and controlling the amount of the buffer system added so that the mass percentage content of minoxidil in the prepared anti-hair loss composition is 4.7%.

[0041] (5) Wash the packaging material with purified water in advance, drain the water, dry it in an oven at 72°C for 25 minutes, and take it out to cool it down for later use. Use a disposable pipette to divide the sample according to the filling amount on a clean workbench. After the sample is divided, store it in a refrigerator at 7°C; the resulting composition is counted as "Composition 1".

[0042] Embodiment 2:

[0043] This example is a control experiment of Example 1, and is carried out according to the same steps and conditions as Example 1, except that in addition to using an equal amount of the regulator metronidazole, an inhibitor (Sophora japonica extract) is also used. The specific implementation is as follows:

[0044] (1) The raw materials are weighed according to the following mass ratio: 1 part of minoxidil, 0.3 parts of a regulator (metronidazole); and an inhibitor (Sophora japonica extract) in an amount 2.3 times (0.69 parts) the mass of metronidazole;

[0045] (2) Measure the excipients according to the following mass ratio: 1 part of polysorbate, 1.2 parts of glycine, 2.4 parts of trehalose, and 0.04 parts of sodium hyaluronate;

[0046] (3) mixing the auxiliary material and the solvent glycerol in a mass ratio of 1:0.4 to obtain a buffer system;

[0047] (4) adding the buffer system to the raw materials and mixing them evenly, and controlling the amount of the buffer system added so that the mass percentage content of minoxidil in the prepared anti-hair loss composition is 4.7%.

[0048] (5) Wash the packaging material with purified water in advance, drain the water, dry it in an oven at 72°C for 25 minutes, and take it out to cool it down for later use. Use a disposable pipette to divide the sample according to the filling amount on a clean workbench. After the sample is divided, store it in a refrigerator at 7°C; the resulting composition is counted as "Composition 2".

[0049] Embodiment three:

[0050] This example is a control experiment of Example 1, and is carried out according to the same steps and conditions as Example 1, except that in addition to using an equal amount of the regulator metronidazole, an inhibitor (South African leaf dry powder) is also used. The specific implementation method is as follows:

[0051] (1) The raw materials are measured according to the following mass ratio: 1 part of minoxidil, 0.3 parts of a regulator (metronidazole); and an inhibitor (South African leaf dry powder) in an amount 2.3 times the mass of metronidazole;

[0052] (2) Measure the excipients according to the following mass ratio: 1 part of polysorbate, 1.2 parts of glycine, 2.4 parts of trehalose, and 0.04 parts of sodium hyaluronate;

[0053] (3) mixing the auxiliary material and the solvent glycerol in a mass ratio of 1:0.4 to obtain a buffer system;

[0054] (4) adding the buffer system to the raw materials and mixing them evenly, and controlling the amount of the buffer system added so that the mass percentage content of minoxidil in the prepared anti-hair loss composition is 4.7%.

[0055] (5) Wash the packaging material with purified water in advance, drain the water, dry it in an oven at 72°C for 25 minutes, and take it out to cool it down for later use. Use a disposable pipette to divide the sample according to the filling amount on a clean workbench. After the sample is divided, store it in a refrigerator at 7°C; the resulting composition is counted as "Composition 3".

[0056] Embodiment 4:

[0057] This example is a control experiment of Example 1, and is carried out according to the same steps and conditions as Example 1, except that in addition to using an equal amount of the regulator metronidazole, a composite inhibitor is also used. The specific implementation is as follows:

[0058] (1) The raw materials are measured according to the following mass ratio: 1 part of minoxidil, 0.3 parts of a regulator (metronidazole); and a composite inhibitor with a mass of 2.3 times that of metronidazole; wherein the composite inhibitor is composed of a Sophora japonica flower extract and South African leaf dry powder in a mass ratio of 1:0.5;

[0059] (2) Measure the excipients according to the following mass ratio: 1 part of polysorbate, 1.2 parts of glycine, 2.4 parts of trehalose, and 0.04 parts of sodium hyaluronate;

[0060] (3) mixing the auxiliary material and the solvent glycerol in a mass ratio of 1:0.4 to obtain a buffer system;

[0061] (4) adding the buffer system to the raw materials and mixing them evenly, and controlling the amount of the buffer system added so that the mass percentage content of minoxidil in the prepared anti-hair loss composition is 4.7%.

[0062] (5) Wash the packaging material with purified water in advance, drain the water, dry it in an oven at 72°C for 25 minutes, and take it out to cool it down for later use. Use a disposable pipette to divide the sample according to the filling amount on a clean workbench. After the sample is divided, store it in a refrigerator at 7°C; the resulting composition is counted as "Composition 4".

[0063] Embodiment five:

[0064] This example is a control experiment of Example 1, and is carried out according to the same steps and conditions as Example 1, except that only the composite inhibitor is used, and no regulator is used. The specific implementation method is as follows:

[0065] (1) The raw materials were measured according to the following mass ratio: 1 part of minoxidil and 0.69 parts of a composite inhibitor (2.3 times the mass of metronidazole in Example 1); the composite inhibitor was composed of a Sophora japonica flower extract and South African leaf dry powder in a mass ratio of 1:0.5;

[0066] (2) Measure the excipients according to the following mass ratio: 1 part of polysorbate, 1.2 parts of glycine, 2.4 parts of trehalose, and 0.04 parts of sodium hyaluronate;

[0067] (3) mixing the auxiliary material and the solvent glycerol in a mass ratio of 1:0.4 to obtain a buffer system;

[0068] (4) adding the buffer system to the raw materials and mixing them evenly, and controlling the amount of the buffer system added so that the mass percentage content of minoxidil in the prepared anti-hair loss composition is 4.7%.

[0069] (5) Wash the packaging material with purified water in advance, drain the water, dry it in an oven at 72°C for 25 minutes, and take it out to cool it down for later use. Use a disposable pipette to divide the sample according to the filling amount on a clean workbench. After the sample is divided, store it in a refrigerator at 7°C; the resulting composition is counted as "Composition 5".

[0070] Comparative Example 1:

[0071] This example is a control experiment of Example 1, and is carried out according to the same steps and conditions as Example 1, except that no regulator and composite inhibitor are used. The specific implementation method is as follows:

[0072] (1) Take the excipients according to the following mass ratio: 1 part of polysorbate, 1.2 parts of glycine, 2.4 parts of trehalose, and 0.04 parts of sodium hyaluronate;

[0073] (2) mixing the auxiliary material and the solvent glycerol in a mass ratio of 1:0.4 to obtain a buffer system;

[0074] (3) adding the buffer system to minoxidil and mixing them evenly, and controlling the amount of the buffer system added so that the mass percentage of minoxidil in the prepared anti-hair loss composition is 4.7%.

[0075] (4) Wash the packaging material with purified water in advance, drain the water, dry it in an oven at 72°C for 25 minutes, and take it out to cool it down for later use. Use a disposable pipette to divide the sample according to the filling amount on a clean workbench. After the sample is divided, store it in a refrigerator at 7°C; the resulting composition is counted as "Composition 0".

[0076] Comparative experiment on the effect of inhibiting scalp oil secretion:

[0077] 1. Experimental design:

[0078] 90 patients with seborrheic alopecia were recruited, aged 31 to 58 years old, all male, with regular lifestyle and avoiding strenuous exercise, excessive sun exposure and staying up late.

[0079] Patients were not allowed to use any anti-hair loss preparations within one week before the test. Patients were required to wash their hair with commercially available shampoo as usual 24 hours before the test. They were not allowed to wash or comb their hair from the time of washing their hair to the 24 hours before the test. This was to test the normal scalp oil secretion level of patients when they were not using anti-hair loss preparations. The test results were required to be between 850 and 1100 μg / cm 2 If it is not within this range, the recruitment object needs to be changed. The detection method is as follows.

[0080] The test group was randomly divided into 6 groups, namely A, B, C, D, E, and F, with 15 people in each group. The average scalp oil secretion level before medication in each group was calculated and recorded in Table 1.

[0081] The above-mentioned A, B, C, D, E, and F groups of patients were treated with the above-mentioned composition 0, composition 1, composition 2, composition 3, composition 4, and composition 5, respectively. The specific method is: at 10:00-11:00 a.m. and 3:00-4:00 p.m. every day, 8 g of the corresponding composition was evenly applied to the affected area (only the right side of the affected area was applied) for each group of patients, and the application was continued for 15 days. During the application period, the hair was washed according to the daily shampooing method before taking the medicine in the morning every 2 days, and the scalp oil secretion was tested 24 hours after washing the hair on the 16th day; the test method and data processing method are shown below, and the test results are shown in Table 1.

[0082] At the same time, during the period of medication, patients in groups B, C, D, E, and F were also treated with "Composition 0" applied to the left side of the affected area in the same manner and in the same amount until the end of the experiment, and whether there was a significant difference in the improvement of hair loss on the left and right sides of the affected area of ​​patients in groups B, C, D, E, and F was observed, and recorded in Table 1.

[0083] 2. Detection methods and data statistics:

[0084] Roll the oil strip into a ring shape, make it cross the medication site (i.e. the right side of the affected area) and contact the patient's scalp for 10 seconds, then put the oil strip flat into the slider of the Meibometer MB560 scalp oil tester, push the slider into the instrument, and use the instrument to derive the scalp oil content. After testing 5 times in different parts (i.e. the non-overlapping parts on the right side of the affected area), take the average value as the input value. Then add the input values ​​of the scalp oil content of 15 patients in each group and calculate the average value, which is recorded in Table 1.

[0085] Table 1 Scalp oil secretion test results

[0086]

[0087] It can be seen from the data of Group 1 in Table 1 that after continuous use of "Composition 0", the scalp oil secretion of the test group was only reduced by 53.3 μg / cm 2 , showed no significant changes.

[0088] It can be seen from the data of Group 2 in Table 1 that after continuous use of "Composition 1", the scalp oil secretion of the test group decreased by 141.5 μg / cm 2 , which is significantly improved compared with the first group of data. It can be seen that metronidazole in the anti-hair loss composition containing minoxidil has a certain improvement effect on the inhibition of scalp oil secretion in patients with seborrheic alopecia, which may be related to the fact that metronidazole, as an antibacterial drug, improves the overall ecological environment of the scalp after medication.

[0089] From the data of groups 2, 5, and 6 in Table 1, it can be seen that when the dosage of the regulator and the combined inhibitor remains unchanged, the oil reduction of metronidazole alone is 141.5 μg / cm 2 , while the reduction of combined inhibitor alone was 173.4 μg / cm 2 If the two are used together, the theoretical reduction should be less than 314.9μg / cm 2 , while the actual measured reduction was 430.5 μg / cm 2 , far exceeding expectations, indicating that the regulator and the composite inhibitor of the present invention have an obvious synergistic effect in inhibiting scalp oil secretion in patients with seborrheic alopecia in the anti-hair loss composition containing minoxidil.

[0090] From the data of groups 3, 4, and 6 in Table 1, it can be seen that when the dosage of the regulator and the inhibitor is exactly the same, the oil reduction of the inhibitor by adding the Sophora japonica extract alone is 210.8 μg / cm 2 The oil reduction of the composite inhibitor with South African leaf dry powder added alone was 183.9μg / cm 2 If the two are mixed in a ratio of 1:0.5, the theoretical reduction should be 201.8μg / cm 2 , while the actual measured reduction was 430.5 μg / cm 2 , which is 113.3% higher than the theoretical value. It can be seen that the components contained in the composite inhibitor of the present invention have an obvious synergistic effect in inhibiting the scalp oil secretion of patients with seborrheic alopecia in the anti-hair loss composition containing minoxidil.

Claims

1. A method for preparing an anti-hair loss composition containing metronidazole, characterized in that: The production raw material formula includes minoxidil, a regulator and pharmaceutically acceptable excipients; the mass ratio of the minoxidil to the regulator is 1:0.1-0.4; and the regulator includes metronidazole.

2. The method for preparing the anti-hair loss composition containing metronidazole according to claim 1, characterized in that: The production raw material formula also includes a composite inhibitor, and the mass ratio of metronidazole to the composite inhibitor is 1:1.5-4.

5.

3. The method for preparing the anti-hair loss composition containing metronidazole according to claim 2, characterized in that: The composite inhibitor includes a Sophora japonica flower extract.

4. The method for preparing the anti-hair loss composition containing metronidazole according to claim 3, characterized in that: The Sophora japonica extract is prepared according to the following method: S1, soaking Sophora japonica flowers in water, adding acetic acid bacteria, and cultivating at 25-33°C for 2-5 days to obtain a mother solution; the mass ratio of acetic acid bacteria to Sophora japonica flowers is 1:5×10 5 ~2×10 6 ; S2, heating the mother liquor to 93-96° C., recovering the generated steam to obtain a reflux liquid; S3, concentrating and drying the reflux liquid at 85-92° C. until the water content is less than 5%, thereby obtaining the product.

5. The method for preparing the anti-hair loss composition containing metronidazole according to claim 3, characterized in that: The composite inhibitor is composed of a Sophora japonica flower extract and South African leaf dry powder in a mass ratio of 1:0.2-1.

6. The method for preparing the anti-hair loss composition containing metronidazole according to claim 5, characterized in that: The South African leaf dry powder is prepared according to the following method: A. Wash and crush the South African leaves and put them into a sealable container, add a saturated ammonium chloride solution, the mass of which is 1% to 3% of the mass of the South African leaves, mix well, seal the container, and let it stand at room temperature for 7 to 15 days to obtain a mixture; B. freeze-drying the mixture at -12 to -35°C until the moisture content is less than 3% to obtain a freeze-dried material; C. Grind the freeze-dried material into powder.

7. The method for preparing the anti-hair loss composition containing metronidazole according to any one of claims 1 to 6, characterized in that: The pharmaceutically acceptable excipients include an anti-adsorption agent, a pH buffer, a stabilizer and a viscosity enhancer; the mass percentage content of minoxidil in the anti-hair loss composition containing metronidazole is 1% to 8%.

8. The method for preparing the anti-hair loss composition containing metronidazole according to claim 7, characterized in that: The pharmaceutically acceptable excipients include the following components in the following mass proportions: 1 part of polysorbate, 0.6-1.5 parts of glycine, 2-4 parts of trehalose, and 0.01-0.1 parts of sodium hyaluronate.

9. The method for preparing the anti-hair loss composition containing metronidazole according to any one of claims 1 to 6 and 8, characterized in that: The method also includes the step of measuring the raw materials according to the production raw material formula and then uniformly mixing them.

10. An anti-hair loss composition containing metronidazole obtained by the preparation method of an anti-hair loss composition containing metronidazole according to any one of claims 1 to 9.

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