An external use traditional Chinese medicine ointment composition and a preparation method thereof

Abstract

This application relates to the field of pharmaceutical technology, specifically disclosing a topical traditional Chinese medicine ointment composition and its preparation method. The topical traditional Chinese medicine ointment composition is made from the following raw materials in parts by weight: 1.8-2.2 parts of pH-responsive traditional Chinese medicine nanocarrier powder, 4-5 parts of glycerin, 4.5-5.5 parts of functionalized layered liquid crystal precursor nanoparticle dispersion, 28-32 parts of intelligent responsive matrix, and 2.5-3.5 parts of phase change isolating microparticles. The preparation method is as follows: the pH-responsive traditional Chinese medicine nanocarrier powder is dispersed in glycerin, then the intelligent responsive matrix is ​​added under stirring for emulsification, and after cooling, the functionalized layered liquid crystal precursor nanoparticle dispersion and phase change isolating microparticles are added and mixed evenly to obtain the final product. The topical traditional Chinese medicine ointment composition of this application can provide immediate barrier strengthening and targeted treatment during the irritation period of moisture / high pH, ​​while reducing intervention and promoting skin self-repair during the recovery period of dry / normal pH.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical technology, and more specifically, to a topical Chinese medicine ointment composition and its preparation method. Background Technology

[0002] Diaper rash, also known as diaper dermatitis, is a common inflammatory skin disease in infants and young children, with an incidence rate as high as 25%-35%. Its pathological basis is that the skin in the diaper area is in a special microenvironment with a closed, moist, and high pH value for a long time, and is continuously or repeatedly stimulated by various factors such as urine, feces, friction, and microorganisms.

[0003] Diaper rash begins with "moisture" and "chemical irritation": urine and sweat cause excessive hydration of the skin, weakening the connections between stratum corneum cells and making them more susceptible to friction damage. The occlusive nature of diapers (especially disposable diapers) creates a high-humidity microenvironment, further exacerbating the decline in skin barrier function. Digestive enzymes in feces (such as proteases and lipases) can directly break down skin proteins and lipids, damaging the barrier. Urea in urine is decomposed by bacteria to produce ammonia, causing the skin surface pH to rise from the normal slightly acidic to slightly alkaline. The alkaline environment not only directly irritates the skin but also activates enzymes in feces, exacerbating their destructive effects and promoting the proliferation of opportunistic pathogens (such as Staphylococcus aureus) and fungi (such as Candida albicans), leading to infectious diaper rash.

[0004] Currently, diaper rash care products on the market can be divided into two categories. One category consists of passive isolation products, which form an inert, hydrophobic physical barrier on the skin surface, passively blocking irritants from contacting the skin. However, when the skin is dry, this thick layer of oil or powder may excessively seal the skin, affecting normal skin respiration and heat dissipation. More importantly, when urine wets the skin, its isolation effect is rapidly weakened by moisture, and it cannot respond to pH changes by releasing anti-inflammatory components. Furthermore, it has almost no active repair effect on existing inflammation and barrier structure damage, belonging to passive protection that "treats the symptoms but not the root cause." The other category consists of active treatment products, which exert anti-inflammatory and anti-infective effects through drug components. These products are mostly passively released, continuing to release drugs during dry, non-irritating intervals, which may lead to unnecessary skin absorption, increasing the risk of local side effects, and cannot provide immediate and enhanced isolation protection during peak urine wetness periods. Both of these have significant limitations.

[0005] Therefore, there is an urgent need to propose a solution to address the aforementioned technical problems. Summary of the Invention

[0006] In order to provide immediate barrier strengthening and targeted treatment during the irritation period of humid / high pH, ​​while reducing intervention and promoting skin self-repair during the recovery period of dry / normal pH, this application provides a topical Chinese medicine ointment composition and its preparation method.

[0007] In a first aspect, this application provides a topical traditional Chinese medicine ointment composition, which adopts the following technical solution: A topical Chinese medicine ointment composition, made from raw materials comprising the following parts by weight: pH-responsive traditional Chinese medicine nanocarrier powder 1.8-2.2 parts; 4-5 parts glycerin; Functionalized layered liquid crystal precursor nanoparticle dispersion, 4.5-5.5 parts; 28-32 portions of intelligent response matrix; Phase change isolation microparticles: 2.5-3.5 parts; The pH-responsive traditional Chinese medicine nanocarrier powder is obtained by mixing and adsorbing traditional Chinese medicine extract with aminated mesoporous silica nanoparticles, and then coating the surface with carboxymethyl chitosan solution. The functionalized layered liquid crystal precursor nanoparticle dispersion was obtained by dissolving ceramide, cholesterol and fatty acid in anhydrous ethanol, injecting it into an aqueous phase containing poloxamer 188, magnetically stirring, removing the ethanol by rotary evaporation, and then mixing it with an equal volume of glycerol monooleate / phytanetriol melt and homogenizing it under high pressure. The intelligent response matrix is ​​obtained by adding an aqueous phase mixture of carboxymethyl chitosan, methacrylate-acrylate copolymer and water to an oil phase mixture of comfrey oil, petrolatum, Span 80, glyceryl monostearate and PEGylated beeswax by heating and melting under stirring, followed by emulsification and homogenization. The phase change isolation microparticles are obtained by immersing hydrophobic silica aerogel microspheres in an ethanol dispersion containing organically modified montmorillonite, followed by ultrasonic treatment, filtration, washing, and drying.

[0008] By employing the above technical solutions, for pH-responsive traditional Chinese medicine nanocarrier powders, aminated mesoporous silica provides extremely high drug loading capacity, while carboxymethyl chitosan, acting as a pH-sensitive "gating" agent, not only improves the easy oxidation and instability of traditional Chinese medicine components but also enables accelerated large-scale release only under alkaline stimulation, avoiding large-scale ineffective release during the dry period and reducing potential irritation to healthy skin, thus improving efficacy and safety. For functionalized layered liquid crystal precursor nanoparticles, ceramides, cholesterol, and fatty acids are used to directly replenish and repair the damaged lipid structure of the stratum corneum. Combined with the liquid crystal structure formed by glyceryl monooleate / phytanetriol, it exhibits extremely high biocompatibility and permeability. For the smart responsive matrix, carboxymethyl chitosan and methacrylic acid copolymer form a thixotropic gel, which, as a pH-sensitive polymer, can change under weakly alkaline conditions. The hydrophilic modified lipid-based oil-phase mixture, composed of comfrey oil, petrolatum, Span 80, glyceryl monostearate, ethylparaben, and PEGylated beeswax, not only provides broad-spectrum anti-inflammatory and soothing effects but also, after forming an oil-in-water (O / W) emulsion, provides a stable platform for the controlled release of pH-responsive traditional Chinese medicine nanocarrier powder. For the hydrophobic silica aerogel in the phase change isolating microparticles, it provides a static hydrophobic barrier, while organically modified montmorillonite swells upon contact with water, dynamically enhancing the isolation density and forming a dynamic physical barrier.

[0009] During the humid / high pH stimulation period, the "gating" of pH-responsive TCM nanocarrier powder is opened. The carboxymethyl chitosan coating dissolves in an alkaline environment, accelerating the release of herbal extracts from the mesoporous silica, directly neutralizing the alkaline environment, inhibiting fecal enzyme activity, and killing pathogens. Functionalized layered liquid crystal precursor nanoparticles rapidly self-assemble under the influence of moisture, forming a layered liquid crystal structure highly similar to the stratum corneum, temporarily repairing the damaged barrier like a "liquid bandage" and blocking further penetration of irritants. The carboxymethyl chitosan and methacrylic acid copolymer in the intelligent response matrix both contain a large number of carboxyl groups. When the skin surface is weakly alkaline, the carboxyl groups deprotonate, and the molecular chains extend due to electrostatic repulsion, greatly increasing hydrophilicity, causing the aqueous droplets to swell, "opening" the channels, accelerating the release of internal active ingredients, and also firmly locking in moisture to prevent backflow and excessive skin hydration. The organic montmorillonite in the phase change isolating microparticles absorbs water and swells, forming a "micro-airbag" physical barrier on the skin surface. Simultaneously, the microparticle structure changes, enhancing the isolation density and preventing irritant penetration. This rapidly activates the "defense-treatment" mode.

[0010] During the recovery period in a dry / normal pH environment, the pH-responsive TCM nanocarrier powder tends to stabilize, enabling controlled release of TCM extracts. This avoids unnecessary drug exposure and potential irritation during the dry period, significantly reducing the risk of side effects. The functionalized layered liquid crystal precursor nanoparticle dispersion continuously releases physiological lipids such as ceramides and cholesterol, penetrating deep into the stratum corneum to play a role in skin barrier repair. The viscosity of the intelligent responsive matrix decreases, no longer sealing the skin, allowing the skin to breathe and dissipate heat normally. In the weakly acidic environment of normal skin, the carboxyl grouping of carboxymethyl chitosan and methacrylic acid copolymer causes molecular chain contraction, reducing the release of internal active ingredients. Phase change isolates the evaporation of water in the microparticles, restoring the porous hydrophobic structure and high breathability. This switches to a "low-intervention repair mode," returning the initiative to the skin's own repair mechanism, truly achieving a combination of treatment and nourishment.

[0011] Therefore, the above-mentioned topical Chinese medicine ointment composition constructs an intelligent ointment system that can synergistically respond and perform multiple care tasks in stages. It provides immediate barrier strengthening and targeted treatment during the irritation period of humidity / high pH, ​​while reducing intervention and promoting skin self-repair during the recovery period of dryness / normal pH. Overall, it has excellent and significant application effects.

[0012] Preferably, the herbal extract is prepared from raw materials comprising the following parts by weight: Gallnut 4-7 parts; 2-4 parts rhubarb; 2-4 parts of Euphorbia humifusa; The specific extraction procedure is as follows: Gallnut, rhubarb, and Euphorbia humifusa are mixed with 10-12 times their weight of water and extracted at 55-65℃ for 10-14 hours. After centrifugation, the mixture is filtered and the filtrate is concentrated to a relative density of 1.05-1.10 to obtain the Chinese herbal extract.

[0013] By adopting the above technical solution, the combination of gallnut, rhubarb, and euphorbia humifusa constructs a "natural defense network" against the diaper rash microenvironment from three dimensions: physical barrier, chemical environment, and biological infection. In the extraction process, low-temperature extraction preserves the activity of heat-sensitive antibacterial components to the greatest extent and avoids the degradation of efficacy caused by high temperature. The extract is concentrated to a relative density of 1.05-1.10 (semi-fluid), which has a suitable viscosity and is convenient for subsequent use.

[0014] Preferably, the aminated mesoporous silica nanoparticles have a particle size of 80-150 nm and a pore size of 5-8 nm.

[0015] By adopting the above technical solution, the 5-8nm pore size acts like a "large net" that can capture small and medium-sized molecules at the same time, while the overall particle size of 80-150nm ensures that each carrier particle has enough channels (high specific surface area) to achieve high drug loading. At the same time, the above specifications enable the carboxymethyl chitosan coating layer to form a uniform and moderately thick "shell", which has good compatibility with the pH response mechanism.

[0016] Preferably, the preparation operation of the pH-responsive traditional Chinese medicine nanocarrier powder is as follows: Aminated mesoporous silica nanoparticles were dispersed in an acetate-sodium acetate buffer solution, and then a traditional Chinese medicine extract was added. The mixture was stirred at 180-220 rpm for 6-8 hours at 35-45℃ in the dark. After centrifugation to collect the solid particles, they were redispersed in a 0.5-1% (w / v) carboxymethyl chitosan aqueous solution and stirred at 100-150 rpm for 1.5-2 hours at 25-35℃. Finally, the mixture was centrifuged, washed with water, and freeze-dried to obtain a pH-responsive traditional Chinese medicine nanocarrier powder.

[0017] By adopting the above technical solution, the surface of aminated mesoporous silica is kept positively charged in the acetate-sodium acetate buffer solution, which generates strong electrostatic adsorption with the negatively charged Chinese medicine components, thereby improving the drug loading efficiency from the source. Then, low temperature and light protection and medium speed and long-term stirring are used to maximize drug loading and stability. Then, a low concentration of carboxymethyl chitosan aqueous solution is used to ensure the formation of a thin coating layer, avoiding excessive thickness that would lead to sluggish pH response. In this way, a pH-responsive Chinese medicine nanocarrier powder with excellent application quality and stability can be obtained.

[0018] Preferably, in the functionalized layered liquid crystal precursor nanoparticle dispersion, the molar ratio of ceramide, cholesterol and fatty acid is 1:(0.6-0.8):(0.8-1.2); and the total weight of ceramide, cholesterol and fatty acid to the weight ratio of poloxamer 188 is 1:(4.5-5.5).

[0019] By adopting the above technical solution, the above ratio of ceramides, cholesterol, and fatty acids can more effectively promote the orderly stacking of lipid bilayers, making it particularly suitable for rapid "repair" of damaged skin (such as diaper rash), rather than just moisturizing. Regarding the weight ratio of the total weight of ceramides, cholesterol, and fatty acids to poloxamer 188, if the poloxamer ratio is too low, nanoparticles are prone to agglomeration during application and cannot form a stable dispersion. If the poloxamer ratio is too high, the surfactant layer may be too thick. The range of 1:(4.5-5.5) avoids these two extremes, ensuring stable storage and smooth conversion to play a stabilizing role during use.

[0020] Preferably, the weight parts of each raw material in the aqueous mixture are as follows: 4.5-5.5 parts of carboxymethyl chitosan; 2-3 parts of methacrylic acid-acrylate copolymer; 280-300 parts water; The weight parts of each raw material in the oil phase mixture are as follows: Comfrey oil 280-320 parts; Vaseline 130-170 servings; The score is 80-75-85. 90-110 parts of glyceryl monostearate; Ethylparaben 0.4-0.5 parts; 45-55 parts of PEGylated beeswax; The weight ratio of the aqueous phase mixture to the oil phase mixture is 1:(2.4-2.6).

[0021] By employing the above technical solutions, the proportions of the corresponding raw materials in the aqueous phase mixture are sufficient to form a continuous hydrogel network, providing enough pH-responsive sites without affecting emulsification due to excessive viscosity, and ensuring a "rigid yet flexible" structure, allowing the ointment to reversibly "breathe" (swell / shrink) with pH changes. In the oil phase mixture, under the above proportions, comfrey oil serves as the main oil phase, providing both medicinal efficacy and acting as a lipid solvent; petrolatum ensures the ointment has sufficient "thickness" and adhesion, forming a physical shield; Span 80 ensures the emulsion does not separate at high temperatures / centrifugation; glyceryl monostearate synergistically reduces interfacial tension with Span 80 and significantly improves the consistency and stability of the ointment; PEGylated beeswax enhances its water-binding ability and alters its microstructure when skin hydration (humidity) increases; thus, a biomimetic barrier of "strong sealing + anti-inflammation" can be created. The ratio of the aqueous phase mixture to the oil phase mixture, while ensuring the W / O structure, "encapsulates" as much of the hydrogel phase as possible, providing sufficient reaction space for pH response, and exhibiting excellent sealing and isolation effects as well as a pleasant feel when applied to the skin.

[0022] Preferably, the hydrophobic silica aerogel microspheres have a particle size of 20-50 μm; the organically modified montmorillonite has a particle size of 2-5 μm and an interlayer spacing of 2.2-2.5 nm.

[0023] By adopting the above technical solution, the hydrophobic silica aerogel microspheres can maintain their particle shape after absorbing liquid, forming a compressible "air cushion" between the skin and the diaper. This not only isolates friction but also allows gas exchange (breathability) and ensures that the organically modified montmorillonite can accurately remove chemical irritants that cause skin pH increase and barrier damage, rather than simply relying on thick oils for blocking. This allows the two to construct a composite phase change isolation system of "micron-level porous framework + nano-level sheet intercalation", thus exerting excellent effects.

[0024] Preferably, the preparation operation of the phase change isolating microparticles is as follows: Organically modified montmorillonite was dispersed in anhydrous ethanol to obtain an ethanol dispersion containing organically modified montmorillonite at a mass-volume ratio of 2-5%. Then, hydrophobic silica aerogel microspheres were immersed in the dispersion and ultrasonically treated at 40-50 kHz for 20-30 min. After vacuum filtration, washing with filtered ethanol, and drying, phase change isolation microparticles were obtained.

[0025] By adopting the above technical solution, the montmorillonite sheets are first fully dissociated in ethanol to avoid aggregation. Then, during ultrasonic treatment, the montmorillonite nanosheets are forced to penetrate deep into the three-dimensional network of the aerogel and "get stuck" at the intersection of the channels, generating strong physical adsorption. Next, during vacuum extraction, the montmorillonite dispersion is rapidly passed through the aerogel framework, causing the sheets to be directionally deposited in the channels, forming a dense internal "nanofilter". At the same time, excess liquid is removed to avoid overfilling and loss of porosity. In this way, an excellent "microsphere-sheet" multi-level composite structure can be constructed to ensure the excellent function of the phase change isolation particles.

[0026] Secondly, this application provides a method for preparing a topical traditional Chinese medicine ointment composition, using the following technical solution: A method for preparing a topical traditional Chinese medicine ointment composition includes the following steps: (1) Prepare raw materials containing pH-responsive traditional Chinese medicine nanocarrier powder, glycerol, functionalized layered liquid crystal precursor nanoparticle dispersion, intelligent response matrix and phase change isolation microparticles according to the formula ratio; (2) Disperse pH-responsive Chinese medicine nanocarrier powder in glycerin, then add smart response matrix under stirring for emulsification, and after cooling, add functionalized layered liquid crystal precursor nanoparticle dispersion and phase change isolation microparticles. After mixing evenly, a Chinese medicine ointment composition is obtained.

[0027] In summary, this application has the following beneficial effects: The topical Chinese medicine ointment composition of this application, while retaining the classic Chinese medicine components, innovatively introduces a three-layer intelligent response system: an intelligent response matrix composed of pH-sensitive polymers and hydrophilic modified lipids; a pH-responsive mesoporous silica nanoparticle carrier and a layered liquid crystal precursor nanoparticle carrier respectively loaded with Chinese medicine active ingredients and skin barrier repair lipids; and phase change isolation microparticles composed of hydrophobic silica aerogel loaded with modified montmorillonite. Thus, after application, it can dynamically adjust its barrier isolation performance and drug release behavior according to the changes in humidity and pH of the skin surface, so as to provide immediate barrier strengthening and targeted treatment during the irritation period of humid / high pH, ​​while reducing intervention and promoting skin self-repair during the recovery period of dry / normal pH. Detailed Implementation

[0028] The present application will be further described in detail below with reference to the embodiments.

[0029] Unless otherwise specified, all raw materials used in the embodiments and comparative examples of this application are commercially available.

[0030] Comfrey oil is obtained by extracting comfrey and sesame oil at a weight ratio of 1:5. The specific operation is as follows: extract with 5 times the amount of sesame oil as comfrey, control the temperature below 60℃, extract for 7 days, and then filter. The modified montmorillonite was obtained by modification with dimethyloctadecylammonium chloride; Hydrophobic silica aerogel microspheres were first prepared by sol-gel method combined with supercritical drying, and then modified with octadecyltrimethoxysilane for hydrophobicity modification. The methacrylate-acrylate copolymer is Eutech L100-55; The fatty acid is linoleic acid.

[0031] Preparation examples of raw materials and / or intermediates Preparation Example 1 A traditional Chinese medicine extract, the raw materials and their corresponding weight parts are shown in Table 1, and it is prepared by the following steps: Gallnut, rhubarb, and Euphorbia humifusa were mixed with 11 times their weight of water and extracted at 60°C for 12 hours. After centrifugation and filtration, the filtrate was concentrated to a relative density of 1.075 to obtain the herbal extract.

[0032] Preparation Examples 2-3 A traditional Chinese medicine extract differs from Preparation Example 1 in that its raw materials and corresponding weight parts are shown in Table 1.

[0033] Table 1. Raw materials and corresponding weight parts (parts / kg) for preparation examples 1-3.

[0034] Preparation Example 4 A traditional Chinese medicine extract, which differs from Preparation Example 1, is prepared by the following steps: Gallnut, rhubarb, and Euphorbia humifusa were mixed with 10 times their weight of water and extracted at 55°C for 14 hours. After centrifugation and filtration, the filtrate was concentrated to a relative density of 1.05 to obtain the herbal extract.

[0035] Preparation Example 5 A traditional Chinese medicine extract, which differs from Preparation Example 1, is prepared by the following steps: Gallnut, rhubarb, and Euphorbia humifusa were mixed with 12 times their weight of water and extracted at 65°C for 10 hours. After centrifugation and filtration, the filtrate was concentrated to a relative density of 1.10 to obtain the herbal extract.

[0036] Example Example 1

[0037] A topical traditional Chinese medicine ointment composition, the raw materials and their corresponding weight parts are shown in Table 2, and it is prepared by the following steps: (1) Prepare raw materials containing pH-responsive traditional Chinese medicine nanocarrier powder, glycerol, functionalized layered liquid crystal precursor nanoparticle dispersion, intelligent response matrix and phase change isolation microparticles according to the formula ratio; (2) Disperse the pH-responsive Chinese medicine nanocarrier powder in glycerol and stir at 1000 rpm for 15 min. Then, add the smart response matrix under stirring for emulsification. The emulsification temperature is 60℃, the speed is 3500 rpm, and the time is 20 min. After cooling to 30℃, add the functionalized layered liquid crystal precursor nanoparticle dispersion and phase change isolation microparticles. Stir at 200 rpm for 25 min. After mixing evenly, the Chinese medicine ointment composition is obtained.

[0038] Note: The pH-responsive traditional Chinese medicine nanocarrier powder mentioned above was obtained by mixing and adsorbing traditional Chinese medicine extracts with aminated mesoporous silica nanoparticles, followed by surface coating with carboxymethyl chitosan solution. The specific preparation method is as follows: Aminated mesoporous silica nanoparticles were dispersed in an acetate-sodium acetate buffer solution at a ratio of 1 g: 35 mL, and then a traditional Chinese medicine extract was added. The mixture was stirred at 200 rpm for 7 h at 40 °C in the dark. After centrifugation to collect the solid particles, they were redispersed in a 0.75% (w / v) carboxymethyl chitosan aqueous solution and stirred at 125 rpm for 1.75 h at 30 °C. Finally, the mixture was centrifuged (12000 rpm, 10 min), washed with water, and freeze-dried (-50 °C, 24 h) to obtain a pH-responsive traditional Chinese medicine nanocarrier powder. The herbal extract used was obtained from Preparation Example 1. The weight ratio of aminated mesoporous silica nanoparticles to herbal extract was 3:2, and the particle size of the aminated mesoporous silica nanoparticles was 115 nm and the pore size was 6.5 nm.

[0039] Functionalized layered liquid crystal precursor nanoparticle dispersions were prepared by dissolving a mixture of ceramide, cholesterol, and fatty acids in anhydrous ethanol at a ratio of 1 g: 50 mL, injecting the mixture into an aqueous phase containing poloxamer 1880 at a mass concentration of 5%, magnetically stirring, removing the ethanol by rotary evaporation, and then mixing it with an equal volume of glyceryl monooleate / phytanetriol melt (glyceryl monooleate and phytanetriol in a weight ratio of 6:1). The mixture was homogenized under high pressure (800 bar, 3 cycles) at a constant temperature of 60 °C and then cooled to 25 °C. In the functionalized layered liquid crystal precursor nanoparticle dispersion, the molar ratio of ceramide, cholesterol, and fatty acid is 1:0.7:1; the total weight ratio of ceramide, cholesterol, and fatty acid to poloxamer 188 is 1:5.

[0040] The intelligent response matrix is ​​obtained by adding an aqueous phase mixture (60°C) of carboxymethyl chitosan, methacrylate-acrylate copolymer and water to an oil phase mixture (75°C) of comfrey oil, petrolatum, Span 80, glyceryl monostearate, ethylparaben and PEGylated beeswax by heating and melting, under stirring, followed by emulsification (5000 rpm, 5 min) and homogenization (400 bar, 4 cycles). The raw materials and their corresponding weight parts in the aqueous phase mixture are shown in Table 3, and the raw materials and their corresponding weight parts in the oil phase mixture are shown in Table 4. The weight ratio of the aqueous phase mixture to the oil phase mixture is 1:2.5.

[0041] Phase change isolating microparticles were prepared by immersing hydrophobic silica aerogel microspheres in an ethanol dispersion containing organically modified montmorillonite, followed by ultrasonic treatment, filtration, washing, and drying. The specific preparation method is as follows: Organically modified montmorillonite was dispersed in anhydrous ethanol and treated at 10,000 rpm for 5 min to obtain an ethanol dispersion containing organically modified montmorillonite at a mass-volume ratio of 3.5%. Then, hydrophobic silica aerogel microspheres were immersed in the dispersion and ultrasonicated at 45 kHz for 25 min. After vacuum filtration, washing with filtered ethanol, and drying (drying at 60℃ and -0.095 MPa for 12 h), phase change isolation microparticles were obtained. The weight ratio of the above-mentioned organically modified montmorillonite and hydrophobic silica aerogel microspheres is 1:9, and the particle size of the hydrophobic silica aerogel microspheres is 35 μm; the particle size of the organically modified montmorillonite is 3.5 μm, and the interlayer spacing is 2.35 nm.

[0042] Example 2-3

[0043] A topical Chinese medicine ointment composition differs from Example 1 in that its raw materials and corresponding weight parts are shown in Table 2.

[0044] Table 2. Raw materials and corresponding weight parts (parts / kg) for the preparation of Examples 1-3

[0045] Example 4

[0046] A topical traditional Chinese medicine ointment composition differs from Example 1 in that the pH-responsive traditional Chinese medicine nanocarrier powder is prepared as follows: Aminated mesoporous silica nanoparticles were dispersed in an acetate-sodium acetate buffer solution at a ratio of 1 g: 35 mL, and then a traditional Chinese medicine extract was added. The mixture was stirred at 180 rpm for 8 h at 35 °C in the dark. After centrifugation to collect the solid particles, the mixture was redispersed in a 0.5% (w / v) carboxymethyl chitosan aqueous solution and stirred at 100 rpm for 2 h at 35 °C. Finally, the mixture was centrifuged (12000 rpm, 10 min), washed with water, and freeze-dried (-50 °C, 24 h) to obtain a pH-responsive traditional Chinese medicine nanocarrier powder.

[0047] Example 5

[0048] A topical traditional Chinese medicine ointment composition differs from Example 1 in that the pH-responsive traditional Chinese medicine nanocarrier powder is prepared as follows: Aminated mesoporous silica nanoparticles were dispersed in an acetate-sodium acetate buffer solution at a ratio of 1 g: 35 mL, and then a traditional Chinese medicine extract was added. The mixture was stirred at 220 rpm for 6 h at 45 °C in the dark. After centrifugation to collect the solid particles, the mixture was redispersed in a 1% (w / v) carboxymethyl chitosan aqueous solution and stirred at 150 rpm for 1.5 h at 25 °C. Finally, the mixture was centrifuged (12000 rpm, 10 min), washed with water, and freeze-dried (-50 °C, 24 h) to obtain a pH-responsive traditional Chinese medicine nanocarrier powder.

[0049] Example 6

[0050] A topical Chinese medicine ointment composition differs from Example 1 in that the aminated mesoporous silica nanoparticles have a particle size of 80 nm and a pore size of 5 nm.

[0051] Example 7

[0052] A topical Chinese medicine ointment composition differs from Example 1 in that the aminated mesoporous silica nanoparticles have a particle size of 150 nm and a pore size of 8 nm.

[0053] Example 8

[0054] A topical Chinese medicine ointment composition differs from Example 1 in that the molar ratio of ceramide, cholesterol, and fatty acid in the functionalized layered liquid crystal precursor nanoparticle dispersion is 1:0.6:0.8; and the total weight ratio of ceramide, cholesterol, and fatty acid to poloxamer 188 is 1:4.5.

[0055] Example 9

[0056] A topical Chinese medicine ointment composition differs from Example 1 in that the molar ratio of ceramide, cholesterol, and fatty acid in the functionalized layered liquid crystal precursor nanoparticle dispersion is 1:0.8:1.2; and the total weight ratio of ceramide, cholesterol, and fatty acid to poloxamer 188 is 1:5.5.

[0057] Examples 10-11

[0058] A topical Chinese medicine ointment composition differs from Example 1 in that the raw materials and their corresponding weight parts in the aqueous phase mixture are shown in Table 3.

[0059] Table 3. Raw materials and their corresponding weight parts (parts / kg) in the aqueous mixtures of Examples 1 and 10-11

[0060] Examples 12-13

[0061] A topical Chinese medicine ointment composition differs from Example 1 in that the raw materials and their corresponding weight parts in the oil phase mixture are shown in Table 4.

[0062] Table 4. Raw materials and their corresponding weight parts (parts / kg) in the oil phase mixtures of Examples 1, 12-13

[0063] Example 14

[0064] A topical Chinese medicine ointment composition differs from Example 1 in that the weight ratio of the aqueous phase mixture and the oil phase mixture is 1:2.4.

[0065] Example 15

[0066] A topical Chinese medicine ointment composition differs from Example 1 in that the weight ratio of the aqueous phase mixture and the oil phase mixture is 1:2.6.

[0067] Example 16

[0068] A topical traditional Chinese medicine ointment composition differs from Example 1 in that the phase change isolating microparticles are obtained by immersing hydrophobic silica aerogel microspheres in an ethanol dispersion containing organically modified montmorillonite, followed by ultrasonic treatment, filtration, washing, and drying. The specific preparation method is as follows: Organically modified montmorillonite was dispersed in anhydrous ethanol and treated at 10,000 rpm for 5 min to obtain an ethanol dispersion containing 2% organically modified montmorillonite by mass volume. Then, hydrophobic silica aerogel microspheres were immersed in the dispersion and ultrasonicated at 50 kHz for 20 min. After vacuum filtration, washing with filtered ethanol, and drying (drying at 60℃ and -0.095 MPa for 12 h), phase change isolation microparticles were obtained.

[0069] Example 17

[0070] A topical traditional Chinese medicine ointment composition differs from Example 1 in that the phase change isolating microparticles are obtained by immersing hydrophobic silica aerogel microspheres in an ethanol dispersion containing organically modified montmorillonite, followed by ultrasonic treatment, filtration, washing, and drying. The specific preparation method is as follows: Organically modified montmorillonite was dispersed in anhydrous ethanol and treated at 10,000 rpm for 5 min to obtain an ethanol dispersion containing organically modified montmorillonite at a mass-volume ratio of 5%. Then, hydrophobic silica aerogel microspheres were immersed in the dispersion and ultrasonically treated at 40 kHz for 30 min. After vacuum filtration, washing with filtered ethanol, and drying (drying at 60℃ and -0.095 MPa for 12 h), phase change isolation microparticles were obtained.

[0071] Example 18

[0072] A topical Chinese medicine ointment composition differs from Example 1 in that the hydrophobic silica aerogel microspheres have a particle size of 20 μm; the organically modified montmorillonite has a particle size of 2 μm and an interlayer spacing of 2.2 nm.

[0073] Example 19

[0074] A topical Chinese medicine ointment composition differs from Example 1 in that the hydrophobic silica aerogel microspheres have a particle size of 50 μm; the organically modified montmorillonite has a particle size of 5 μm and an interlayer spacing of 2.5 nm.

[0075] Example 20

[0076] A topical Chinese medicine ointment composition differs from Example 1 in that the Chinese medicine extract used is obtained from Preparation Example 2.

[0077] Example 21

[0078] A topical Chinese medicine ointment composition differs from Example 1 in that the Chinese medicine extract used is obtained from Preparation Example 3.

[0079] Example 22

[0080] A topical Chinese medicine ointment composition differs from Example 1 in that the Chinese medicine extract used is obtained from Preparation Example 4.

[0081] Example 23

[0082] A topical Chinese medicine ointment composition differs from Example 1 in that the Chinese medicine extract used is obtained from Preparation Example 5.

[0083] Comparative Example Comparative Example 1 A topical Chinese medicine ointment composition, which differs from Example 1 in that, by weight, it comprises: 4 parts of Gallnut, 2 parts of Rhubarb, 2 parts of Euphorbia humifusa, 2 parts of Lithospermum erythrorhizon, 1 part of Beeswax, 14 parts of edible sesame oil, 2 parts of Vaseline, 2 parts of Glycerin, 1 part of Span 80, 1 part of Glyceryl monostearate, and 0.01 parts of Ethylparaben. The preparation steps are as follows: Add 12 times the amount of water to gallnut, rhubarb, and euphorbia humifusa, maintain the temperature at 60℃, and extract for 12 hours. After standing or centrifugation, filter and concentrate the filtrate to a clear extract with a relative density of 1.05 (measured at 55-60℃). Set aside. Separately, place edible sesame oil in a pot and heat to 60℃. Then, extract comfrey in the edible sesame oil for 7 days. Filter to obtain comfrey oil. Oil phase preparation: Add beeswax to the comfrey oil, heat to 120℃ for sterilization for 30 minutes, then add petrolatum, Span 80, glyceryl monostearate, and ethylparaben. Dissolve and stir well, and keep warm at 60℃. Aqueous phase preparation: Disperse the above clear extract in glycerin, heat to dissolve and sterilize, and keep warm at 60℃. Emulsification: Slowly add the glycerin clear extract solution to the oil phase solution for preliminary emulsification. After cooling to 40℃, homogenize the emulsion to obtain the final product.

[0084] Performance testing Test samples: The topical Chinese medicine ointment compositions obtained in Examples 1-23 were selected as test samples 1-23, and the topical Chinese medicine ointment composition obtained in Comparative Example 1 was selected as control sample 1.

[0085] Experimental methods: (1) pH-responsive drug release test: Prepare release medium phosphate buffer (PBS), prepare two types of pH=5.5 and pH=7.4 respectively, and dialysis bags (molecular weight cutoff: 10000Da, boiled and soaked in deionized water before use). A measured amount of the topical Chinese medicine ointment composition was evenly spread onto an inert support mesh (nylon mesh), then transferred and sealed in a pretreated dialysis bag to obtain the test sample. The sample was then placed in a dissolution vessel containing 900 mL of PBS release medium at pH 5.5 and pH 7.4, respectively, and placed in a constant temperature shaker at 32°C (100 rpm). After 6 hours, the sample solution was aspirated from the external medium of the dissolution vessel, filtered through a 0.22 μm microporous membrane, and the characteristic components of the Chinese medicine were detected using high performance liquid chromatography (HPLC). Finally, the release rate of the Chinese medicine components was calculated as: (measured drug concentration × volume of release medium) / total amount of drug loaded in the ointment.

[0086] (2) Humidity-responsive barrier test: A certain amount of desiccant was added to the permeable cup, and the simulated skin substrate was tightly covered and sealed at the mouth of the cup. Then, the topical Chinese medicine ointment composition was evenly applied to the simulated skin substrate. Next, the permeable cup was placed in a constant temperature and humidity chamber with the conditions set as follows: temperature 32℃ and relative humidity 95% to simulate a high humidity environment. After 30 minutes, the total weight of the permeable cup was weighed, and the weight increase was calculated. Then, the water vapor transmission rate was calculated. Water vapor transmission rate = weight increase / (permeable area × time). Finally, the barrier efficiency improvement rate (%) was calculated. Barrier efficiency improvement rate (%) = [1 - (water vapor transmission rate after 30 minutes of treatment) / (initial water vapor transmission rate before treatment)] × 100%.

[0087] After performing the above tests on test samples 1-23 and control sample 1, the test results are recorded in Table 5.

[0088] Table 5. Test results of test samples 1-23 and control sample 1

[0089] As can be seen from Examples 1-23 and Comparative Example 1, and Table 5, compared with the traditional topical Chinese medicine ointment composition in Comparative Example 1, this application, while retaining the classic Chinese medicine components, uses a three-layer intelligent response system consisting of a smart response matrix composed of pH-sensitive polymers and hydrophilic modified lipids, a pH-responsive mesoporous silica nanoparticle carrier loaded with Chinese medicine active ingredients and skin barrier repair lipids respectively, a layered liquid crystal precursor nanoparticle carrier, and phase change isolation microparticles composed of hydrophobic silica aerogel loaded with modified montmorillonite. This results in a significantly lower release rate of Chinese medicine components at normal pH, avoiding a large amount of ineffective release and reducing potential irritation to healthy skin, thus improving efficacy and safety. At high pH, ​​the release rate of Chinese medicine components increases significantly, which is more conducive to exerting efficacy. Furthermore, after stimulation in a high-humidity environment, its ability to block water vapor penetration is increased by 70%, thereby achieving immediate barrier strengthening and targeted treatment during the humid / high pH stimulation period, while reducing intervention and promoting skin self-repair during the dry / normal pH recovery period. Overall, it has excellent and significant application effects.

[0090] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A topical traditional Chinese medicine ointment composition, characterized in that, Made from the following ingredients in parts by weight: pH-responsive traditional Chinese medicine nanocarrier powder 1.8-2.2 parts; 4-5 parts glycerin; Functionalized layered liquid crystal precursor nanoparticle dispersion, 4.5-5.5 parts; 28-32 portions of intelligent response matrix; Phase change isolation microparticles: 2.5-3.5 parts; The pH-responsive traditional Chinese medicine nanocarrier powder is obtained by mixing and adsorbing traditional Chinese medicine extract with aminated mesoporous silica nanoparticles, and then coating the surface with carboxymethyl chitosan solution. The functionalized layered liquid crystal precursor nanoparticle dispersion was obtained by dissolving ceramide, cholesterol and fatty acid in anhydrous ethanol, injecting it into an aqueous phase containing poloxamer 188, magnetically stirring, removing the ethanol by rotary evaporation, and then mixing it with an equal volume of glycerol monooleate / phytanetriol melt and homogenizing it under high pressure. The intelligent response matrix is ​​obtained by adding an aqueous phase mixture of carboxymethyl chitosan, methacrylate-acrylate copolymer and water to an oil phase mixture of comfrey oil, petrolatum, Span 80, glyceryl monostearate and PEGylated beeswax by heating and melting under stirring, followed by emulsification and homogenization. The phase change isolation microparticles are obtained by immersing hydrophobic silica aerogel microspheres in an ethanol dispersion containing organically modified montmorillonite, followed by ultrasonic treatment, filtration, washing, and drying.

2. The topical Chinese medicine ointment composition according to claim 1, characterized in that: The herbal extract is made from raw materials comprising the following parts by weight: Gallnut 4-7 parts; 2-4 parts rhubarb; 2-4 parts of Euphorbia humifusa; The specific extraction procedure is as follows: Gallnut, rhubarb, and Euphorbia humifusa are mixed with 10-12 times their weight of water and extracted at 55-65℃ for 10-14 hours. After centrifugation, the mixture is filtered and the filtrate is concentrated to a relative density of 1.05-1.10 to obtain the Chinese herbal extract.

3. The topical Chinese medicine ointment composition according to claim 1, characterized in that: The aminated mesoporous silica nanoparticles have a particle size of 80-150 nm and a pore size of 5-8 nm.

4. The topical Chinese medicine ointment composition according to claim 1, characterized in that: The preparation procedure for the pH-responsive traditional Chinese medicine nanocarrier powder is as follows: Aminated mesoporous silica nanoparticles were dispersed in an acetate-sodium acetate buffer solution, and then a traditional Chinese medicine extract was added. The mixture was stirred at 180-220 rpm for 6-8 hours at 35-45℃ in the dark. After centrifugation to collect the solid particles, they were redispersed in a 0.5-1% (w / v) carboxymethyl chitosan aqueous solution and stirred at 100-150 rpm for 1.5-2 hours at 25-35℃. Finally, the mixture was centrifuged, washed with water, and freeze-dried to obtain a pH-responsive traditional Chinese medicine nanocarrier powder.

5. The topical Chinese medicine ointment composition according to claim 1, characterized in that: In the functionalized layered liquid crystal precursor nanoparticle dispersion, the molar ratio of ceramide, cholesterol and fatty acid is 1:(0.6-0.8):(0.8-1.2); the total weight of ceramide, cholesterol and fatty acid to the weight ratio of poloxamer 188 is 1:(4.5-5.5).

6. The topical Chinese medicine ointment composition according to claim 1, characterized in that: The weight parts of each raw material in the aqueous mixture are as follows: 4.5-5.5 parts of carboxymethyl chitosan; 2-3 parts of methacrylic acid-acrylate copolymer; 280-300 parts water; The weight parts of each raw material in the oil phase mixture are as follows: Comfrey oil 280-320 parts; Vaseline 130-170 servings; The score is 80-75-85. 90-110 parts of glyceryl monostearate; Ethylparaben 0.4-0.5 parts; 45-55 parts of PEGylated beeswax; The weight ratio of the aqueous phase mixture to the oil phase mixture is 1:(2.4-2.6).

7. The topical Chinese medicine ointment composition according to claim 1, characterized in that: The hydrophobic silica aerogel microspheres have a particle size of 20-50 μm; the organically modified montmorillonite has a particle size of 2-5 μm and an interlayer spacing of 2.2-2.5 nm.

8. The topical Chinese medicine ointment composition according to claim 1, characterized in that: The preparation steps for the phase change isolation microparticles are as follows: Organically modified montmorillonite was dispersed in anhydrous ethanol to obtain an ethanol dispersion containing organically modified montmorillonite at a mass-volume ratio of 2-5%. Then, hydrophobic silica aerogel microspheres were immersed in the dispersion and ultrasonically treated at 40-50 kHz for 20-30 min. After vacuum filtration, washing with filtered ethanol, and drying, phase change isolation microparticles were obtained.

9. The method for preparing the topical traditional Chinese medicine ointment composition according to claim 1, characterized in that: Includes the following steps: (1) Prepare raw materials containing pH-responsive traditional Chinese medicine nanocarrier powder, glycerol, functionalized layered liquid crystal precursor nanoparticle dispersion, intelligent response matrix and phase change isolation microparticles according to the formula ratio; (2) Disperse pH-responsive Chinese medicine nanocarrier powder in glycerin, then add smart response matrix under stirring for emulsification, and after cooling, add functionalized layered liquid crystal precursor nanoparticle dispersion and phase change isolation microparticles. After mixing evenly, a Chinese medicine ointment composition is obtained.

Images