Oral-administration and external-use combined preparation for treating leucoderma and preparation method of oral-administration and external-use combined preparation
By developing a combination preparation for the treatment of vitiligo with domestic and external use, using nano-based technology and the combination effect of polymelanin tablets, the problems of large side effects, poor efficacy and prone to recurrence of existing treatment methods have been solved, and significant Treatment effects and long-term skin recovery.
Patent Information
- Application Number
- CN202411669399.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-21
- Publication Date
- 2025-02-11
AI Technical Summary
The existing treatment methods for vitiligo have problems such as great side effects, poor efficacy and recurrence, which is difficult to meet the patients' long-term treatment needs.
Develop a combination preparation for the treatment of vitiligo by taking oral and external use, including skin antibacterial solution and polymelanin tablets. Skin antibacterial solution improves the permeability and stability of traditional Chinese medicine ingredients through nanoification technology and promotes melanin production; polymelanin tablets inhibit the apoptosis of melanocytes and improves skin microcirculation by providing a variety of nutrients and regulating immune function.
This combination preparation can effectively improve the lesions of skin recovery in patients with vitiligo, promote melanin production, significantly improve the therapeutic effect and reduce the risk of recurrence.
Smart Images
Figure CN119405774A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to an oral and external composite preparation for treating vitiligo and a preparation method thereof. Technical Background
[0002] Vitiligo is a skin depigmentation disease. The main pathogenesis is that the epidermal melanocytes produce too much ROS (reactive oxygen species) when producing melanin. The body's insufficient antioxidant capacity causes oxidative stress response, directly damages lipids and proteins, and initiates autoimmune response to mediate cytotoxicity to melanocytes, leading to melanocyte dysfunction and even apoptosis, and eventually forming white spot lesions, which bring serious psychological burden to patients. Existing treatment methods include drug therapy, phototherapy, immunomodulation, surgical transplantation, etc. Commonly used drugs such as glucocorticoids, calcineurin inhibitors, psoralen, etc., although they can promote melanin production or regulate the immune system to a certain extent, have large side effects and the efficacy varies from person to person, so it is difficult to meet the long-term treatment needs of patients. In addition, although phototherapy can activate the proliferation and migration of melanocytes, it is easy to cause skin inflammation, redness and swelling during treatment, and the treatment cycle is long and the cost is high. Therefore, vitiligo treatment still faces great challenges and bottlenecks.
[0003] Chinese medicine is rich in a variety of active ingredients with anti-inflammatory, antioxidant, microcirculation-promoting, and immune-regulating effects. It can bind to multiple targets in the body and use different signal pathways to achieve the purpose of treating diseases. In recent years, it has been gradually used to treat vitiligo and other complex diseases with multiple causes. Therefore, through the scientific combination of Chinese medicine and modern extraction technology, it is expected to develop a safe and efficient compound therapeutic preparation that combines oral and topical use, synergistically enhances the effect, and effectively promotes melanin production, repairs the skin, and achieves a better vitiligo treatment effect.
[0004] At present, the drugs for treating vitiligo on the market have relatively single functions, poor efficacy and are prone to relapse. Therefore, there is an urgent need to provide a combination preparation that can simultaneously supply nutrients, regulate the body's immune function and stimulate the activity of melanocytes, so as to achieve the purpose of treating both the symptoms and the root cause. Summary of the invention
[0005] In view of the above situation, the present invention provides a combined preparation for treating vitiligo for internal and external use and a preparation method thereof. The main ingredients of the external preparation are the traditional Chinese medicines Angelica dahurica, Sophora flavescens, dried ginger, Cnidium monnieri, Tribulus terrestris, Cuscuta australis, safflower and Astragalus membranaceus. A skin antibacterial liquid is prepared by a dispersion medium containing materials such as nano-titanium dioxide, an emulsifier and natural plant oil, which can promote the transdermal absorption of local drugs, accelerate the production of melanin, and achieve a local therapeutic effect. The main ingredients of the internal preparation are collagen peptides, calcium carbonate, microcrystalline cellulose, soybean peptide powder, D-mannitol, mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, Angelica dahurica, wolfberry, lotus seed, Poria cocos, black beans, walnuts, black sesame, zinc gluconate and sodium selenite. The multi-black peptide tablets are made by a certain preparation process, which provide the body with a variety of nutrients, regulate immunity and inhibit the activity of lymphocytes and the complement system in the body, help slow down the apoptosis of melanocytes, and improve the skin microcirculation as a whole.
[0006] To achieve the above purpose, the technical solution adopted by the present invention is as follows: The invention provides an oral and external composite preparation for treating vitiligo, the composite preparation comprising a skin antibacterial liquid and multi-black peptide tablets.
[0007] Furthermore, the skin antibacterial liquid is prepared from the following raw materials in parts by weight: 10 parts of traditional Chinese medicine concentrate, 3-5 parts of polyethylene glycol 200, 1.5-3 parts of nano titanium dioxide, 2 parts of grape seed oil, 1 part of polydimethylsiloxane and 15-25 parts of anhydrous ethanol.
[0008] Furthermore, the Chinese medicine concentrate is prepared from the following raw materials: angelica dahurica, sophora flavescens, dried ginger, cnidium monnieri, tribulus terrestris, dodder seed, safflower, astragalus and 50% ethanol, and the mass ratio of angelica dahurica, sophora flavescens, dried ginger, cnidium monnieri, tribulus terrestris, dodder seed, safflower and astragalus is 2-4:1-3:1-3:0.7-2:0.5-2:0.5-1:0.3-1:0.2-1.
[0009] Preferably, the nano titanium dioxide crystal form is anatase, and the molecular particle size is 20-50 nm.
[0010] Furthermore, the multi-black peptide tablets are prepared from the following raw materials in parts by weight: 4-6 parts of Chinese medicine dry paste powder, 5-8 parts of collagen peptide, 3-5 parts of soybean peptide powder, 2 parts of calcium carbonate, 12-20 parts of microcrystalline cellulose, 4 parts of D-mannitol, 0.5 parts of zinc gluconate, 0.1 parts of sodium selenite and 4-6 parts of purified water.
[0011] Furthermore, the Chinese medicine dry paste powder is prepared from the following raw materials: mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica, wolfberry, lotus seed, Poria, black bean, walnut, black sesame and purified water, and the mass ratio of mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica, wolfberry, lotus seed, Poria, black bean, walnut and black sesame is 4-8:6-7:3-5:4:2:2:4-6:2:3:3:3:5-6:3:6-8.
[0012] The preparation method of the Chinese medicine concentrated solution comprises the following steps: A1: Weigh angelica dahurica, sophora flavescens, dried ginger, cnidium monnieri, tribulus terrestris, dodder seed, safflower and astragalus in a mass ratio of 2-4:1-3:1-3:0.7-2:0.5-2:0.5-1:0.3-1:0.2-1, grind them in a grinder and pass through a 40-mesh sieve to obtain Chinese medicine powder; A2: Soak the Chinese medicine powder obtained in step A1 in 50% ethanol for 30 min at a mass volume ratio of 1 g:10 mL, and extract by heating reflux for 1 h at an extraction temperature of 80°C. After the extraction, separate the extract and the drug residue with filter cloth, add the same volume of 50% ethanol as that used in the first extraction to the drug residue, extract again, filter, and combine the extracts filtered twice to obtain a combined extract; A3: Use a rotary evaporator to concentrate the combined extract obtained in step A2 at a temperature of 30°C and a speed of 60 r / min. The rotary evaporator is connected to an ethanol coolant circulation pump and the temperature is set to -10°C. Concentrate to a concentration of 1.0-1.1 g of Chinese medicine powder per milliliter to obtain a Chinese medicine concentrate.
[0013] The preparation method of the Chinese medicine dry paste powder comprises the following steps: B1: Weigh mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica dahurica, wolfberry, lotus seed, poria, black bean, walnut and black sesame according to the mass ratio of 4-8:6-7:3-5:4:2:2:4-6:2:3:3:3:5-6:3:6-8 to obtain a traditional Chinese medicine compound; B2: Put the weighed Chinese medicine compound into a decoction bag, soak it in a casserole for 30 minutes according to the mass ratio of the Chinese medicine compound to purified water of 1:10, and then decoct it in an electric stove. Use an electric stove to heat it. Set the electric stove temperature to 160℃, boil it, and then adjust it to 90℃ and decoct it for 40 minutes. Transfer the decoction liquid out, add the same amount of purified water as the first decoction into the casserole containing the decoction bag, decoct it again at 90℃ for 20 minutes, and combine the two decoction liquids to obtain a combined decoction liquid; B3: Place the combined decoction obtained in step B2 in a 60°C constant temperature water bath for evaporation and concentration. When the decoction is concentrated to a density of 1.10-1.15 g / mL, transfer it to a vacuum drying oven for drying at 60°C, vacuum degree 0.08 MPa, and drying time 12 h to obtain a Chinese medicine dry paste powder.
[0014] The present invention also provides a method for preparing a skin antibacterial liquid for treating vitiligo by a combined oral and external use preparation, which specifically comprises the following steps: (1) Weigh 10 parts of traditional Chinese medicine concentrate, 3-5 parts of polyethylene glycol 200, 1.5-3 parts of nano titanium dioxide, 2 parts of grape seed oil, 1 part of polydimethylsiloxane and 15-25 parts of anhydrous ethanol; (2) adding the Chinese medicine concentrate and nano-titanium dioxide weighed in step (1) into anhydrous ethanol, and performing nano-dispersion treatment for 10 min using an ultrasonic nanomaterial disperser at a frequency of 20 kHz, a power of 280 W, and a temperature of 20° C. to obtain a Chinese medicine nano-dispersion liquid; (3) mixing the polyethylene glycol 200, grape seed oil and polydimethylsiloxane weighed in step (1), and heating the mixture to 40-45° C. in a constant temperature water bath to reduce the viscosity, thereby obtaining an oil phase mixture; (4) slowly adding the TCM nano-dispersion obtained in step (2) to the oil phase mixture obtained in step (3), stirring manually for 3 min, and then emulsifying in a high-pressure homogenizer at a pressure of 1300 bar and a temperature of 50° C. to obtain a TCM emulsion; (5) The traditional Chinese medicine emulsion obtained in step (4) is filtered and sterilized through a 0.22 μm polyethersulfone filter membrane to obtain a skin antibacterial liquid.
[0015] The present invention also provides a method for preparing a multi-black peptide tablet for treating vitiligo as a combined preparation for oral and external use, which specifically comprises the following steps: 1. Weigh 4-6 parts of Chinese medicine dry paste powder, 5-8 parts of collagen peptide, 3-5 parts of soybean peptide powder, 2 parts of calcium carbonate, 4 parts of D-mannitol, 0.5 parts of zinc gluconate and 0.1 parts of sodium selenite, and grind them in a grinder to obtain a pulverized material; Second: Weigh 4-6 parts of purified water as a wetting agent, add the crushed material obtained in step 1 into a high-speed mixing granulator and dry mix for 2 minutes, with the stirring blade rotating at 180 r / min and the cutting knife rotating at 1500 r / min, connect one end of the peristaltic pump rubber tube to the feed port of the high-speed mixing granulator, and put the other end into purified water, with the peristaltic pump rotating at 150 rpm and mixing for 5 minutes to obtain a soft material; 3. The soft material prepared in step 2 was transferred to a fluidized bed and dried for 1 h, with an inlet air temperature of 75°C and a fan frequency of 40 Hz. After cooling to room temperature, dry granules were obtained. Fourth, weigh 12-20 parts of microcrystalline cellulose, and size the dry particles obtained in step 3 and pass them through a 40-mesh sieve to obtain particles I. Use a three-dimensional motion mixer to mix particles I and microcrystalline cellulose for 10 minutes at a spindle speed of 15 r / min to obtain an intermediate; 5: Using a rotary tablet press, the intermediate obtained in step 4 is pressed into tablets with a specification of 0.5 g / tablet and a hardness of 70-90 N to obtain multi-black peptide tablets.
[0016] The beneficial effects achieved by the present invention are as follows: The combined preparation for treating vitiligo prepared by the present invention comprises a skin antibacterial liquid and multi-black peptide tablets, which can perform synergistic treatment from both local and overall aspects, effectively improve the recovery of vitiligo patients' diseased skin, activate tyrosinase activity and promote melanin production, and has a significant effect on the treatment of vitiligo and the inhibition of recurrence. The topical antibacterial liquid for skin contains ingredients such as coumarin, psoralen, flavonoids, polyphenols, alkaloids and volatile oils extracted from traditional Chinese medicines such as Angelica dahurica, Sophora flavescens, Tribulus terrestris and Cnidium monnieri. It has strong antibacterial, antioxidant and melanin-promoting functions. Under the action of oily ingredients such as grape seed oil and polydimethylsiloxane, the nano-sized active ingredients of traditional Chinese medicine have stronger stability and permeability, and the therapeutic effect is enhanced; in addition, the oily ingredients can help nano-titanium dioxide to reside in the gaps on the surface of the affected skin for a long time, forming a hydrophobic film protective layer, which has the advantages of not being afraid of water washing, moisturizing and reducing the loss of active ingredients. In addition, nano-titanium dioxide can effectively absorb and scatter ultraviolet rays while transmitting visible light without affecting the normal physiological functions of skin cells, reducing the damage of light to the lesion site, forming a local light effect, further enhancing the activity of photosensitive ingredients such as coumarin and psoralen, stimulating the activity of tyrosinase in melanocytes, and increasing melanin production. The oral multi-black peptide tablets are rich in nutrients such as high-quality proteins, small molecule peptides, vitamins, trace elements and minerals required for melanocyte metabolism. They play a therapeutic role through multiple pathways and mechanisms, fundamentally promoting melanin production and pigmentation. Among them, Chinese medicines such as wolfberry, mulberry, lotus seeds and coix seeds have the function of regulating immunity, which can enhance the ability to resist adverse external factors and help inhibit the recurrence of vitiligo. Chinese medicines such as angelica, poria, black sesame and walnut can effectively remove ROS in the body, and with trace elements such as zinc, sodium and calcium as auxiliary, they can reduce oxidative damage to melanocytes and help maintain the health of the skin. Ingredients such as safflower, jujube kernel and black rice have the function of promoting blood circulation and removing blood stasis, and synergize with coumarin, psoralen and nano-titanium dioxide in the external skin antibacterial liquid to improve skin microcirculation, provide sufficient nutrition and oxygen for melanin production, and accelerate the recovery of pigmentation in the white spot area.
[0017] Compared with the prior art, the combined oral and topical preparation for treating vitiligo provided by the present invention follows the "whole-local" treatment model, effectively solving the problem that vitiligo is difficult to cure and prone to recurrence, and has significant clinical application value. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 This is a flow chart for preparing a combined preparation for oral and external use for treating vitiligo according to the present invention; Figure 2 The in vitro antibacterial rate results of the skin antibacterial liquid of a combined preparation for treating vitiligo for internal and external use prepared in Example 1-3; Figure 3 These are diagrams showing the therapeutic effects of patients using a combined oral and topical preparation for treating vitiligo prepared in Example 1, wherein a, b, c and d are diagrams showing the therapeutic effects of cases 1-4, respectively.
[0019] The accompanying drawings are used to provide further understanding of the present invention and constitute a part of the specification. They are used to explain the present invention together with the embodiments of the present invention and do not constitute a limitation of the present invention. DETAILED DESCRIPTION
[0020] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.
[0021] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein may be applied to the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only and are not intended to limit the content of this application.
[0022] The preparation process in the following examples is referred to Figure 1 Unless otherwise specified, all methods are conventional; the materials used in the following embodiments, unless otherwise specified, are new materials purchased from the market.
[0023] Example 1: This example provides a combined preparation for treating vitiligo for internal and external use, the combined preparation comprising a skin antibacterial liquid and a multi-black peptide tablet, the skin antibacterial liquid comprising the following components in parts by weight: 10 parts of Chinese medicine concentrate, 3 parts of polyethylene glycol 200, 1.5 parts of nano-titanium dioxide, 2 parts of grape seed oil, 1 part of polydimethylsiloxane and 15 parts of anhydrous ethanol, the multi-black peptide tablet comprising the following components in parts by weight: 4 parts of Chinese medicine dry paste powder, 8 parts of collagen peptide, 4 parts of soybean peptide powder, 2 parts of calcium carbonate, 12 parts of microcrystalline cellulose, 4 parts of D-mannitol, 0.5 parts of zinc gluconate, 0.1 parts of sodium selenite and 4 parts of purified water; Furthermore, the method for preparing the Chinese medicine concentrate comprises the following steps: A1: Weigh angelica dahurica, sophora flavescens, dried ginger, cnidium monnieri, tribulus terrestris, dodder seed, safflower, and astragalus in a mass ratio of 2:1:1:0.7:0.5:0.5:0.3:0.2, grind them in a grinder, and pass through a 40-mesh sieve to obtain Chinese medicine powder; A2: Soak the Chinese medicine powder obtained in step A1 in 50% ethanol for 30 min at a mass volume ratio of 1 g:10 mL, and extract by heating reflux for 1 h at an extraction temperature of 80°C. After the extraction, separate the extract and the drug residue with filter cloth, add the same volume of 50% ethanol as that used in the first extraction to the drug residue, extract again, filter, and combine the extracts filtered twice to obtain a combined extract; A3: Use a rotary evaporator to concentrate the combined extract obtained in step A2 at a temperature of 30°C and a speed of 60 r / min. The rotary evaporator is connected to an ethanol coolant circulation pump and the temperature is set to -10°C. Concentrate to a concentration of 1.0-1.1 g of Chinese medicine powder per milliliter to obtain a Chinese medicine concentrate.
[0024] The preparation method of the Chinese medicine dry paste powder comprises the following steps: B1: Weigh mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica dahurica, wolfberry, lotus seed, poria, black bean, walnut and black sesame in a mass ratio of 4:6:3:4:2:2:4:2:3:3:3:5:3:6 to obtain a traditional Chinese medicine compound; B2: Put the weighed Chinese medicine compound into a decoction bag, soak it in a casserole for 30 minutes according to the mass ratio of the Chinese medicine compound to purified water of 1:10, and then decoct it in an electric stove. Use an electric stove to heat it. Set the electric stove temperature to 160℃, boil it, and then adjust the temperature to 90℃ for 40 minutes. Transfer the decoction liquid, add the same amount of purified water as the first decoction into the casserole containing the decoction bag, decoct it again at 90℃ for 20 minutes, and combine the two decoction liquids to obtain a combined decoction liquid; B3: Place the combined decoction obtained in step B2 in a 60°C constant temperature water bath for evaporation and concentration. When the decoction is concentrated to a density of 1.10-1.15 g / mL, transfer it to a vacuum drying oven for drying at 60°C, vacuum degree 0.08 MPa, and drying time 12 h to obtain a Chinese medicine dry paste powder.
[0025] This embodiment also provides a method for preparing a skin antibacterial liquid for the combined preparation for treating vitiligo, which specifically comprises the following steps: (1) Weigh 10 parts of traditional Chinese medicine concentrate, 3 parts of polyethylene glycol 200, 1.5 parts of nano-titanium dioxide, 2 parts of grape seed oil, 1 part of polydimethylsiloxane and 15 parts of anhydrous ethanol; (2) adding the Chinese medicine concentrate and nano-titanium dioxide weighed in step (1) into anhydrous ethanol, and performing nano-dispersion treatment for 10 min using an ultrasonic nanomaterial disperser at a frequency of 20 kHz, a power of 280 W, and a temperature of 20° C. to obtain a Chinese medicine nano-dispersion liquid; (3) mixing the polyethylene glycol 200, grape seed oil and polydimethylsiloxane weighed in step (1), and heating the mixture to 45° C. in a constant temperature water bath to reduce the viscosity, thereby obtaining an oil phase mixture; (4) slowly adding the TCM nano-dispersion obtained in step (2) to the oil phase mixture obtained in step (3), stirring manually for 3 min, and then emulsifying in a high-pressure homogenizer at a pressure of 1300 bar and a temperature of 50° C. to obtain a TCM emulsion; (5) The traditional Chinese medicine emulsion obtained in step (4) is filtered and sterilized through a 0.22 μm polyethersulfone filter membrane to obtain a skin antibacterial liquid.
[0026] This embodiment also provides a method for preparing a multi-black peptide tablet as a combined preparation for oral and external use for treating vitiligo, which specifically comprises the following steps: 1. Weigh 4 parts of Chinese medicine dry powder, 8 parts of collagen peptide, 4 parts of soybean peptide powder, 2 parts of calcium carbonate, 4 parts of D-mannitol, 0.5 parts of zinc gluconate and 0.1 parts of sodium selenite, and grind them in a grinder to obtain a ground material; Second: Weigh 4 parts of purified water as a wetting agent, add the crushed material obtained in step 1 into a high-speed mixing granulator and dry mix for 2 minutes, with the stirring blade rotating at 180 r / min and the cutting knife rotating at 1500 r / min, connect one end of the peristaltic pump rubber tube to the feed port of the high-speed mixing granulator, and put the other end into purified water, with the peristaltic pump rotating at 150 rpm, and mix for 5 minutes to obtain a soft material; 3. The soft material prepared in step 2 was transferred to a fluidized bed and dried for 1 h, with an inlet air temperature of 75°C and a fan frequency of 40 Hz. After cooling to room temperature, dry granules were obtained. Fourth, weigh 12 parts of microcrystalline cellulose, and size the dry particles obtained in step 3 and pass them through a 40-mesh sieve to obtain particles I. Use a three-dimensional motion mixer to mix particles I and microcrystalline cellulose for 10 minutes at a spindle speed of 15 r / min to obtain an intermediate; 5: Using a rotary tablet press, the intermediate obtained in step 4 is pressed into tablets with a specification of 0.5 g / tablet and a hardness of 70-90 N to obtain multi-black peptide tablets.
[0027] Example 2: This example provides a combined preparation for treating vitiligo for internal and external use, the combined preparation comprising a skin antibacterial liquid and a multi-black peptide tablet, the skin antibacterial liquid comprising the following components in parts by weight: 10 parts of Chinese medicine concentrate, 4 parts of polyethylene glycol 200, 2 parts of nano titanium dioxide, 2 parts of grape seed oil, 1 part of polydimethylsiloxane and 20 parts of anhydrous ethanol, the multi-black peptide tablet comprising the following components in parts by weight: 5 parts of Chinese medicine dry paste powder, 7 parts of collagen peptide, 3 parts of soybean peptide powder, 2 parts of calcium carbonate, 20 parts of microcrystalline cellulose, 4 parts of D-mannitol, 0.5 parts of zinc gluconate, 0.1 parts of sodium selenite and 6 parts of purified water; Furthermore, the method for preparing the Chinese medicine concentrate comprises the following steps: A1: Weigh angelica dahurica, sophora flavescens, dried ginger, cnidium monnieri, tribulus terrestris, dodder seed, safflower, and astragalus in a mass ratio of 2:1:1:0.7:0.5:0.5:0.3:0.2, grind them in a grinder, and pass through a 40-mesh sieve to obtain Chinese medicine powder; A2: Soak the Chinese medicine powder obtained in step A1 in 50% ethanol for 30 min at a mass volume ratio of 1 g:10 mL, and extract by heating reflux for 1 h at an extraction temperature of 80°C. After the extraction, separate the extract and the drug residue with filter cloth, add the same volume of 50% ethanol as that used in the first extraction to the drug residue, extract again, filter, and combine the extracts filtered twice to obtain a combined extract; A3: Use a rotary evaporator to concentrate the combined extract obtained in step A2 at a temperature of 30°C and a speed of 60 r / min. The rotary evaporator is connected to an ethanol coolant circulation pump and the temperature is set to -10°C. Concentrate to a concentration of 1.0-1.1 g of Chinese medicine powder per milliliter to obtain a Chinese medicine concentrate.
[0028] The preparation method of the Chinese medicine dry paste powder comprises the following steps: B1: Weigh mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica dahurica, wolfberry, lotus seed, poria, black bean, walnut and black sesame in a mass ratio of 4:6:3:4:2:2:4:2:3:3:3:5:3:6 to obtain a traditional Chinese medicine compound; B2: Put the weighed Chinese medicine compound into a decoction bag, soak it in a casserole for 30 minutes according to the mass ratio of the Chinese medicine compound to purified water of 1:10, and then decoct it in an electric stove. Use an electric stove to heat it. Set the electric stove temperature to 160℃, boil it, and then adjust the temperature to 90℃ for 40 minutes. Transfer the decoction liquid, add the same amount of purified water as the first decoction into the casserole containing the decoction bag, decoct it again at 90℃ for 20 minutes, and combine the two decoction liquids to obtain a combined decoction liquid; B3: Place the combined decoction obtained in step B2 in a 60°C constant temperature water bath for evaporation and concentration. When the decoction is concentrated to a density of 1.10-1.15 g / mL, transfer it to a vacuum drying oven for drying at 60°C, vacuum degree 0.08 MPa, and drying time 12 h to obtain a Chinese medicine dry paste powder.
[0029] This embodiment also provides a method for preparing a skin antibacterial liquid for the combined preparation for treating vitiligo, which specifically comprises the following steps: (1) Weigh 10 parts of traditional Chinese medicine concentrate, 4 parts of polyethylene glycol 200, 2 parts of nano titanium dioxide, 2 parts of grape seed oil, 1 part of polydimethylsiloxane and 20 parts of anhydrous ethanol; (2) adding the Chinese medicine concentrate and nano-titanium dioxide weighed in step (1) into anhydrous ethanol, and performing nano-dispersion treatment for 10 min using an ultrasonic nanomaterial disperser at a frequency of 20 kHz, a power of 280 W, and a temperature of 20° C. to obtain a Chinese medicine nano-dispersion liquid; (3) mixing the polyethylene glycol 200, grape seed oil and polydimethylsiloxane weighed in step (1), and heating the mixture to 45° C. in a constant temperature water bath to reduce the viscosity, thereby obtaining an oil phase mixture; (4) slowly adding the TCM nano-dispersion obtained in step (2) to the oil phase mixture obtained in step (3), stirring manually for 3 min, and then emulsifying in a high-pressure homogenizer at a pressure of 1300 bar and a temperature of 50° C. to obtain a TCM emulsion; (5) The traditional Chinese medicine emulsion obtained in step (4) is filtered and sterilized through a 0.22 μm polyethersulfone filter membrane to obtain a skin antibacterial liquid.
[0030] This embodiment also provides a method for preparing a multi-black peptide tablet as a combined preparation for oral and external use for treating vitiligo, which specifically comprises the following steps: 1. Weigh 5 parts of Chinese medicine dry powder, 7 parts of collagen peptide, 3 parts of soybean peptide powder, 2 parts of calcium carbonate, 4 parts of D-mannitol, 0.5 parts of zinc gluconate and 0.1 parts of sodium selenite, and grind them in a grinder to obtain a pulverized material; Second: Weigh 6 parts of purified water as a wetting agent, add the crushed material obtained in step 1 into a high-speed mixing granulator and dry mix for 2 min, with the stirring blade rotating at 180 r / min and the cutting knife rotating at 1500 r / min, connect one end of the peristaltic pump rubber tube to the feed port of the high-speed mixing granulator, and put the other end into purified water, with the peristaltic pump rotating at 150 rpm, and mix for 5 min to obtain a soft material; 3. The soft material prepared in step 2 was transferred to a fluidized bed and dried for 1 h, with an inlet air temperature of 75°C and a fan frequency of 40 Hz. After cooling to room temperature, dry granules were obtained. Fourth, weigh 20 parts of microcrystalline cellulose, and size the dry particles obtained in step 3 and pass them through a 40-mesh sieve to obtain particles I. Use a three-dimensional motion mixer to mix particles I and microcrystalline cellulose for 10 minutes at a spindle speed of 15 r / min to obtain an intermediate; 5: Using a rotary tablet press, the intermediate obtained in step 4 is pressed into tablets with a specification of 0.5 g / tablet and a hardness of 70-90 N to obtain multi-black peptide tablets.
[0031] Example 3: This example provides a combined preparation for treating vitiligo for internal and external use, the combined preparation comprising a skin antibacterial liquid and a multi-black peptide tablet, the skin antibacterial liquid comprising the following components in parts by weight: 10 parts of Chinese medicine concentrate, 5 parts of polyethylene glycol 200, 3 parts of nano titanium dioxide, 2 parts of grape seed oil, 1 part of polydimethylsiloxane and 25 parts of anhydrous ethanol, the multi-black peptide tablet comprising the following components in parts by weight: 6 parts of Chinese medicine dry paste powder, 5 parts of collagen peptide, 5 parts of soybean peptide powder, 2 parts of calcium carbonate, 15 parts of microcrystalline cellulose, 4 parts of D-mannitol, 0.5 parts of zinc gluconate, 0.1 parts of sodium selenite and 5 parts of purified water; Furthermore, the method for preparing the Chinese medicine concentrate comprises the following steps: A1: Weigh angelica dahurica, sophora flavescens, dried ginger, cnidium monnieri, tribulus terrestris, dodder seed, safflower, and astragalus in a mass ratio of 2:1:1:0.7:0.5:0.5:0.3:0.2, grind them in a grinder, and pass through a 40-mesh sieve to obtain Chinese medicine powder; A2: Soak the Chinese medicine powder obtained in step A1 in 50% ethanol for 30 min at a mass volume ratio of 1 g:10 mL, and extract by heating reflux for 1 h at an extraction temperature of 80°C. After the extraction, separate the extract and the drug residue with filter cloth, add the same volume of 50% ethanol as that used in the first extraction to the drug residue, extract again, filter, and combine the extracts filtered twice to obtain a combined extract; A3: Use a rotary evaporator to concentrate the combined extract obtained in step A2 at a temperature of 30°C and a speed of 60 r / min. The rotary evaporator is connected to an ethanol coolant circulation pump and the temperature is set to -10°C. Concentrate to a concentration of 1.0-1.1 g of Chinese medicine powder per milliliter to obtain a Chinese medicine concentrate.
[0032] The preparation method of the Chinese medicine dry paste powder comprises the following steps: B1: Weigh mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica dahurica, wolfberry, lotus seed, poria, black bean, walnut and black sesame in a mass ratio of 4:6:3:4:2:2:4:2:3:3:3:5:3:6 to obtain a traditional Chinese medicine compound; B2: Put the weighed Chinese medicine compound into a decoction bag, soak it in a casserole for 30 minutes according to the mass ratio of the Chinese medicine compound to purified water of 1:10, and then decoct it in an electric stove. Use an electric stove to heat it. Set the electric stove temperature to 160℃, boil it, and then adjust the temperature to 90℃ for 40 minutes. Transfer the decoction liquid, add the same amount of purified water as the first decoction into the casserole containing the decoction bag, decoct it again at 90℃ for 20 minutes, and combine the two decoction liquids to obtain a combined decoction liquid; B3: Place the combined decoction obtained in step B2 in a 60°C constant temperature water bath for evaporation and concentration. When the decoction is concentrated to a density of 1.10-1.15 g / mL, transfer it to a vacuum drying oven for drying at 60°C, vacuum degree 0.08 MPa, and drying time 12 h to obtain a Chinese medicine dry paste powder.
[0033] This embodiment also provides a method for preparing a skin antibacterial liquid for the combined preparation for treating vitiligo, which specifically comprises the following steps: (1) Weigh 10 parts of traditional Chinese medicine concentrate, 5 parts of polyethylene glycol 200, 3 parts of nano titanium dioxide, 2 parts of grape seed oil, 1 part of polydimethylsiloxane and 25 parts of anhydrous ethanol; (2) adding the Chinese medicine concentrate and nano-titanium dioxide weighed in step (1) into anhydrous ethanol, and performing nano-dispersion treatment for 10 min using an ultrasonic nanomaterial disperser at a frequency of 20 kHz, a power of 280 W, and a temperature of 20° C. to obtain a Chinese medicine nano-dispersion liquid; (3) mixing the polyethylene glycol 200, grape seed oil and polydimethylsiloxane weighed in step (1), and heating the mixture to 45° C. in a constant temperature water bath to reduce the viscosity, thereby obtaining an oil phase mixture; (4) slowly adding the TCM nano-dispersion obtained in step (2) to the oil phase mixture obtained in step (3), stirring manually for 3 min, and then emulsifying in a high-pressure homogenizer at a pressure of 1300 bar and a temperature of 50° C. to obtain a TCM emulsion; (5) The traditional Chinese medicine emulsion obtained in step (4) is filtered and sterilized through a 0.22 μm polyethersulfone filter membrane to obtain a skin antibacterial liquid.
[0034] This embodiment also provides a method for preparing a multi-black peptide tablet as a combined preparation for oral and external use for treating vitiligo, which specifically comprises the following steps: 1. Weigh 6 parts of Chinese medicine dry powder, 5 parts of collagen peptide, 5 parts of soybean peptide powder, 2 parts of calcium carbonate, 4 parts of D-mannitol, 0.5 parts of zinc gluconate and 0.1 parts of sodium selenite, and grind them in a grinder to obtain a pulverized material; Second: Weigh 6 parts of purified water as a wetting agent, add the crushed material obtained in step 1 into a high-speed mixing granulator and dry mix for 2 min, with the stirring blade rotating at 180 r / min and the cutting knife rotating at 1500 r / min, connect one end of the peristaltic pump rubber tube to the feed port of the high-speed mixing granulator, and put the other end into purified water, with the peristaltic pump rotating at 150 rpm, and mix for 5 min to obtain a soft material; 3. The soft material prepared in step 2 was transferred to a fluidized bed and dried for 1 h, with an inlet air temperature of 75°C and a fan frequency of 40 Hz. After cooling to room temperature, dry granules were obtained. Fourth, weigh 15 parts of microcrystalline cellulose, and size the dry particles obtained in step 3 and pass them through a 40-mesh sieve to obtain particles I. Use a three-dimensional motion mixer to mix particles I and microcrystalline cellulose for 10 minutes at a spindle speed of 15 r / min to obtain an intermediate; 5: Using a rotary tablet press, the intermediate obtained in step 4 is pressed into tablets with a specification of 0.5 g / tablet and a hardness of 70-90 N to obtain multi-black peptide tablets.
[0035] Zeta potential and particle size investigation Take the prepared Chinese medicine nano-dispersion liquid of Example 1-3, dilute it 5 times with purified water, take 1 mL of the diluted sample in the particle size sample pool, use the nanoparticle size measuring instrument to detect the particle size in the sample, parallel 3 times, and take the average value; take 200 μL of the diluted sample in the potential sample pool, use the nanoparticle size measuring instrument to detect the particle Zeta potential in the sample, parallel 3 times, and take the average value. The results are shown in Table 1.
[0036] Investigation of antibacterial ability Dissolve the nutrient agar powder in deionized water, sterilize with high pressure steam, prepare the culture medium, cool to 40-45°C, pour the culture medium (about 4 mL) into a sterile culture dish in a clean bench, let it stand and solidify for later use; take the activated Staphylococcus aureus solution and Escherichia coli solution and dilute them to 3×10 8CFU / mL concentration, take 50 μL to be spread on nutrient agar culture dishes, and incubate in a 37°C constant temperature incubator for 24 h; take 100 μL of the skin antibacterial solution prepared in Examples 1-3, spread on culture dishes inoculated with Staphylococcus aureus and Escherichia coli, and continue to incubate in a 37°C constant temperature incubator for 48 h, and each sample is paralleled in triplicate; the blank group is a blank nutrient agar medium without inoculation of bacterial solution and skin antibacterial solution, the control group is inoculated with bacterial solution and sterile PBS solution equal to the skin antibacterial solution, and the experimental group is inoculated with bacterial solution and the skin antibacterial solution prepared in Examples 1-3. The antibacterial rate was calculated by the colony counting method, according to the following formula: Antibacterial rate % = (N 对照 -N 空白 -N 实验 ) / N 对照 ×100%. Take the average value and plot the result. Figure 2 .
[0037] Where N 对照 、N 空白 and N 实验 These are the bacterial colony counts in the culture dishes of the control group, blank group and experimental group, respectively.
[0038] Disintegration time limit study In accordance with the requirements of General Chapter 0921 of the 2020 edition of the Chinese Pharmacopoeia, the multi-black peptide tablets prepared in Examples 1-3 were placed in a 37°C lifting disintegrator, and the time taken for the tablets to completely disintegrate was recorded. Three tablets of each example sample were measured in parallel. The results are shown in Table 2.
[0039] Table 1 Particle size and Zeta potential of TCM nanodispersions
[0040] The results in Table 1 show that the Chinese medicine nano-dispersion prepared by nano-processing the Chinese medicine extracts of Examples 1-3 has a small particle size, strong skin penetration ability, is positively charged as a whole, can adsorb to the negatively charged cell membrane, and effectively act on the cells. In addition, the Chinese medicine nano-dispersion prepared in Example 1 has a small PDI and a more uniform particle size distribution.
[0041] Figure 2 The results showed that the skin antibacterial liquid prepared in Examples 1-3 had a strong effect of inhibiting the growth of Staphylococcus aureus and Escherichia coli, and could improve the local treatment effect of vitiligo and enhance the body's resistance.
[0042] Table 2 Disintegration time of multi-black peptide tablets
[0043] The results in Table 2 show that the multi-black peptide tablets prepared in Examples 1-3 can all be completely disintegrated within 1 minute, and after entering the stomach, they quickly release nutrients for absorption by the body.
[0044] The following is a case description of treatment using a combined oral and topical preparation for treating vitiligo prepared in Example 1.
[0045] Dosage and Administration: Apply the external skin antibacterial liquid to the affected area three times a day, once each time. Stop using if redness or itching occurs. Take the multi-black peptide tablets orally three times a day, two tablets each time, and swallow them.
[0046] Case 1: Chen, female, 44 years old, lesions were distributed on the hands. After using the combined preparation prepared in Example 1 for 8 weeks, the white spots became smaller and lighter until they returned to normal skin color. Figure 3 As shown in a.
[0047] Case 2: Mr. Wang, male, 4 years old, had a large lesion distributed on the trunk. After using the combined preparation prepared in Example 1 for 5 weeks, the white spots became lighter and returned to normal skin color. Figure 3 As shown in b.
[0048] Case 3: Xu, male, 15 years old, lesions were distributed on the thighs. After using the combined preparation prepared in Example 1 for 3 weeks, black circles appeared around the white spots and gradually shrunk inwards. Figure 3 As shown in c.
[0049] Case 4: Mr. Hu, male, 17 years old, had a small lesion on the thigh. After using the combined preparation prepared in Example 1 for 4 weeks, the melanin deposits in the white spots turned black, and the area of the white spots became smaller until it disappeared. Figure 3 As shown in d.
[0050] In summary, through the test results of the embodiments and the treatment effects on patients with vitiligo, the combined preparation for oral and topical treatment of vitiligo prepared by the present invention adopts the nano-preparation process of traditional Chinese medicine to improve the local antibacterial and melanin production capabilities, effectively improves the skin of white spots and restores it to normal, and the orally taken multi-black peptide tablets can supply the body with nutrients, inhibit oxidative stress response and activate the activity of melanocytes, synergize with the external skin antibacterial liquid, improve skin microcirculation, and ultimately cure vitiligo.
[0051] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.
[0052] The present invention and its implementation methods are described above, which is not restrictive. The drawings are only one of the implementation methods of the present invention, and the actual application is not limited thereto. In short, if ordinary technicians in the field are inspired by it and design methods and embodiments similar to the technical solution without creativity without departing from the purpose of the invention, they should all fall within the protection scope of the present invention.
Claims
1. A combined preparation for treating vitiligo for oral and external use, characterized in that: The combined preparation comprises a skin antibacterial solution and a multi-black peptide tablet; The skin antibacterial liquid is prepared from the following raw materials: Chinese medicine concentrate, polyethylene glycol 200, nano titanium dioxide, grape seed oil, polydimethylsiloxane and anhydrous ethanol; The Chinese medicine concentrate is prepared from the following raw materials: Angelica dahurica, Sophora flavescens, dried ginger, Cnidium monnieri, Tribulus terrestris, Cuscuta chinensis, Carthamus tinctorius, Astragalus membranaceus and 50% ethanol, and the specific preparation method is as follows: A1: Weigh angelica dahurica, sophora flavescens, dried ginger, cnidium monnieri, tribulus terrestris, dodder seed, safflower and astragalus, crush and sieve to obtain Chinese medicine powder; A2: adding 50% ethanol to the traditional Chinese medicine powder obtained in step A1 to soak and extract, separating the extract and the residue, adding an equal volume of 50% ethanol to the residue to extract again, filtering, and combining the extracts to obtain a combined extract; A3: Concentrate the combined extract obtained in step A2 to obtain a Chinese medicine concentrate.
2. The combined preparation for treating vitiligo according to claim 1, characterized in that: The multi-black peptide tablets are prepared from the following raw materials: Chinese medicine dry paste powder, collagen peptide, soybean peptide powder, calcium carbonate, microcrystalline cellulose, D-mannitol, zinc gluconate, sodium selenite and purified water; The Chinese medicine dry paste powder is prepared from the following raw materials: mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica dahurica, wolfberry, lotus seed, tuckahoe, black bean, walnut, black sesame and purified water; The preparation method of the Chinese medicine dry paste powder comprises the following steps: B1: Weigh mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica dahurica, wolfberry, lotus seed, poria, black bean, walnut and black sesame to obtain a traditional Chinese medicine compound; B2: soaking and decocting the weighed traditional Chinese medicine compound, transferring the decoction, adding an equal amount of purified water for secondary decoction, and combining the decoctions to obtain a combined decoction; B3: The combined decoction obtained in step B2 is evaporated, concentrated and dried to obtain a Chinese medicine dry paste powder.
3. The combined preparation for treating vitiligo according to claim 1, characterized in that: In step A1, the mass ratio of angelica dahurica, sophora flavescens, dried ginger, cnidium monnieri, tribulus terrestris, dodder seed, safflower and astragalus is 2-4:1-3:1-3:0.7-2:0.5-2:0.5-1:0.3-1:0.2-1, the crushing and screening process uses a crusher and a 40-mesh screen, the mass volume ratio of the traditional Chinese medicine powder and 50% ethanol in step A2 is 1 g:10 mL, the soaking time is 30 min, and the extraction is carried out by heating reflux method, each extraction is 1 h, the temperature is 80°C, and the concentration in step A3 uses a rotary evaporator connected to an ethanol coolant circulation pump, the heating temperature is 30°C, the speed is 60 r / min, the circulation pump temperature is -10°C, and the concentration is to be equivalent to 1.0-1.1g of traditional Chinese medicine powder per milliliter.
4. The combined preparation for treating vitiligo according to claim 2, characterized in that: In step B1, the mass ratio of mulberry, black rice, chestnut, coix seed, jujube seed, laver, oat, angelica dahurica, wolfberry, lotus seed, Poria cocos, black bean, walnut and black sesame is 4-8:6-7:3-5:4:2:2:4-6:2:3:3:3:5-6:3:6-8. In step B2, the mass ratio of the Chinese medicine compound and purified water is 1:
10. The Chinese medicine compound is placed in a decoction bag for 30 min. The electric furnace temperature is set to 160°C for boiling and then adjusted to 90°C for 40 min. The second decoction is 20 min. The evaporation and concentration process in step B3 is carried out in a constant temperature water bath and concentrated to a density of 1.10-1.15 g / mL. The drying process uses a vacuum drying oven with a temperature of 60°C, a vacuum degree of 0.08 MPa, and a drying time of 12 h.
5. A method for preparing a combined preparation for treating vitiligo according to any one of claims 1 to 4, characterized in that: The preparation method of the skin antibacterial liquid comprises the following steps: (1) Weigh Chinese medicine concentrate, polyethylene glycol 200, nano titanium dioxide, grape seed oil, polydimethylsiloxane and anhydrous ethanol; (2) adding the Chinese medicine concentrate and nano-titanium dioxide weighed in step (1) into anhydrous ethanol, and performing nano-dispersion treatment to obtain a Chinese medicine nano-dispersion; (3) mixing the polyethylene glycol 200, grape seed oil and polydimethylsiloxane weighed in step (1), and heating to reduce the viscosity to obtain an oil phase mixture; (4) slowly adding the Chinese medicine nano-dispersion obtained in step (2) to the oil phase mixture obtained in step (3), manually stirring, and emulsifying to obtain a Chinese medicine emulsion; (5) The traditional Chinese medicine emulsion obtained in step (4) is filtered and sterilized to obtain a skin antibacterial liquid.
6. The method for preparing a combined preparation for treating vitiligo for internal and external use according to claim 5, characterized in that: In step (1), the weight proportions of the Chinese medicine concentrate, polyethylene glycol 200, nano titanium dioxide, grape seed oil, polydimethylsiloxane and anhydrous ethanol are 10 parts, 3-5 parts, 1.5-3 parts, 2 parts, 1 part and 15-25 parts respectively; In step (2), the nano-treatment process uses an ultrasonic nano-material disperser, with ultrasound for 10 min, a frequency of 20 kHz, a power of 280 W, and a temperature of 20°C; In step (3), the heating temperature is 40-45°C and is carried out in a constant temperature water bath; In step (4), the stirring time is 3 min, and the emulsification process is carried out in a high-pressure homogenizer at a pressure of 1300 bar and a temperature of 50°C; In step (5), the filtration process uses a 0.22 μm polyethersulfone filter membrane.
7. A method for preparing a combined preparation for treating vitiligo for internal or external use according to any one of claims 1 to 4, characterized in that: The preparation method of the multi-black peptide tablet comprises the following steps:
1. Weigh Chinese medicine dry paste powder, collagen peptide, soybean peptide powder, calcium carbonate, D-mannitol, zinc gluconate and sodium selenite, and grind them to obtain a grinded material; 2. Weigh purified water, dry-mix the crushed material obtained in step 1, and mix the dry-mixed material and purified water by a peristaltic pump to obtain a soft material; 3. Drying and cooling the soft material prepared in step 2 to obtain dry particles; Fourth, weigh microcrystalline cellulose, granulate and sieve the dry particles obtained in step 3 to obtain particles I, and mix particles I and microcrystalline cellulose to obtain an intermediate; Five: The intermediate obtained in step four is pressed into tablets to obtain multi-black peptide tablets.
8. The method for preparing a combined preparation for treating vitiligo for internal and external use according to claim 7, characterized in that: The weight portions of the Chinese medicine dry paste powder, collagen peptide, soybean peptide powder, calcium carbonate, D-mannitol, zinc gluconate, sodium selenite, microcrystalline cellulose and purified water are 4-6 parts, 5-8 parts, 3-5 parts, 2 parts, 4 parts, 0.5 parts, 0.1 parts, 12-20 parts and 4-6 parts respectively; The crushing process described in step 1 uses a crusher; In step 2, the preparation process is carried out in a high-speed mixing granulator, the stirring paddle speed is 180 r / min, the cutting knife speed is 1500 r / min, one end of the peristaltic pump rubber tube is connected to the feed port of the high-speed mixing granulator, and the other end is placed in purified water, the dry mixing time is 2 min, the peristaltic pump speed is 150 rpm, and the purified water is added for mixing time of 5 min; In step 3, the drying process is carried out in a fluidized bed for 1 h, with an inlet air temperature of 75°C and a fan frequency of 40 Hz; In step 4, the sieving screen is 40 mesh, and the mixing process uses a three-dimensional motion mixer with a mixing time of 10 min and a spindle speed of 15 r / min; In step 5, the tableting process uses a rotary tablet press with a specification of 0.5 g / tablet and a hardness of 70-90 N.