A pH-responsive microcapsule coated monitoring agent, and a preparation method and application thereof

Abstract

The application discloses a pH response type microcapsule coated monitoring agent and a preparation method thereof. The microcapsule comprises a core material and a wall material, the core material is one or more compounds of methyl red, bromocresol green and thymol blue, and the wall material is selected from urea-formaldehyde resin, polyurethane resin, gelatin-arabic gum compound or sodium alginate-chitosan compound; the particle size is 5-100 mu m, and the shell thickness is 1-5 mu m. The indicator and the carrier are isolated by the core-shell structure, so that the early reaction and migration color bleeding are avoided; the wall material is resistant to shearing and environmental corrosion; the response time is 5-60 seconds in a liquid medium and 2-30 minutes in a solid carrier; the particle size and the shell thickness can be adjusted as required, and the microcapsule is suitable for various carriers such as sealant, paint, packaging film, wound dressing and concrete; the preparation process is mature, the cost is controllable, and the application is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of functional microcapsule technology, specifically relating to a pH-responsive microcapsule-encapsulated monitoring agent, its preparation method, and its application. Background Technology

[0002] pH value is an important indicator reflecting the acidity or alkalinity of the environment, and it has a wide range of monitoring needs in industrial, food, medical, and environmental protection fields. Current pH monitoring methods mainly include pH test strips, electrochemical probes, and direct addition of indicators. However, pH test strips are only suitable for liquid surface detection and cannot be embedded in materials; electrochemical probes are costly and not suitable for large-area monitoring; and direct addition of indicators suffers from problems such as migration, color bleeding, and reaction with the carrier, limiting their application in complex matrices. Microencapsulation technology can effectively isolate indicators from the external environment. A search revealed existing research on encapsulating indicators in microcapsules. For example, Chinese patent CN115825056A discloses a wide-range pH-changing nanocapsule, whose core material is a mixture of thymol blue, bromocresol green, and bromocresol purple, with a particle size of 150-180 nm. Chinese patent application CN121228542A discloses a microcapsule emulsion with pH indication function, using a polyurethane-polyurea-polyacrylate hybrid shell to encapsulate the pH indicator. Furthermore, CN103169140B discloses an edible microcapsule indicating probiotic activity, which is pH-sensitive and displays different colors depending on changes in external pH. However, existing technologies still have the following shortcomings: (1) the shell is not resistant to carrier stirring and shearing, resulting in a high breakage rate during production; (2) the response speed is difficult to meet the needs of rapid monitoring; (3) different carriers have poor compatibility, requiring redesign for a single scenario; and (4) the preparation process is complex and costly. It is particularly noteworthy that the existing technology has not yet provided a universal pH indicator microcapsule system that can be adapted to both industrial carriers (such as sealants and concrete) and biomedical carriers (such as wound dressings and packaging films), nor has it found a technical solution for systematically adapting particle size and shell thickness for different carrier types. Therefore, developing a pH-responsive microcapsule with stable structure, rapid response, strong adaptability, and mature technology has clear application value. Summary of the Invention

[0003] Purpose of the invention To address the shortcomings of existing technologies, the present invention aims to provide a pH-responsive microcapsule-coated monitoring agent and its preparation method, achieving the following technical effects: By using a core-shell structure and a diverse wall material design, the pH indicator is isolated from the carrier material, preventing premature reaction, migration, and discoloration. The wall material is resistant to carrier environments and agitation and shearing, ensuring structural integrity during production and storage; When exposed to acidic or alkaline media, it rapidly breaks open its shell to release the indicator. The response time in liquid media is ≤60 seconds, and the response time in solid carriers is ≤30 minutes. Particle size and shell thickness can be adjusted as needed to adapt to different types of carriers without interfering with the original performance of the carrier; The preparation process is mature, the cost is controllable, and industrial mass production can be achieved.

[0004] Technical solution To achieve the above objectives, the present invention adopts the following technical solution: (I) Microcapsule structure design Core material: One or more of methyl red, bromocresol green, and thymol blue are selected and blended. The mass ratio of the three is (1-3):(2-5):(1-2), which can achieve segmented colorimetric identification within the pH range of 2-12. pH 2-3: Red (dominated by thymol blue) pH 4–5: Orange-yellow (transition from methyl red and bromocresol green) pH 6–7: Yellow-green (methyl red endpoint, bromocresol green midpoint) pH 8–9: Blue-green (starting with thymol blue, ending with bromocresol blue) pH 10–12: Blue-purple (thymol blue endpoint) The technical advantage of this invention, which selects the above three indicators in combination, lies in the complementary color change ranges of the three: methyl red covers pH 4.4–6.2 (red → yellow), bromocresol green covers pH 3.8–5.4 (yellow → blue), and thymol blue covers pH 1.2–2.8 (red → yellow) and pH 8.0–9.6 (yellow → blue). The combination of these three indicators can form a continuously discernible color gradation within the pH range of 2–12. Although it does not achieve continuous linear color development across all pH levels, it can meet the needs of most industrial and biological monitoring scenarios for distinguishing acid-base changes. Wall material: Selected based on carrier characteristics: Industrial substrates (sealants, anti-corrosion coatings): Urea-formaldehyde resin and polyurethane resin (resistant to organic corrosion and shear strength) are selected. Food / medical carriers (packaging films, wound dressings): Gelatin-gum arabic complex and sodium alginate-chitosan complex (good biocompatibility and biodegradability) are selected. Industrial-grade wall materials can have 5%–10% toughening agents (polyethylene glycol, polypropylene glycol, etc.) added to improve their flexibility; bio-based wall materials can selectively add toughening agents as needed. Particle size and shell thickness matching: When the carrier is a thin-layer material (packaging film, wound dressing): particle size 5-20 μm, shell thickness 1-2 μm (avoid penetrating the carrier). When the carrier is a structural material (concrete, soil conditioner): particle size 50-100μm, shell thickness 3-5μm (to improve shear resistance). When the carrier is a paste-like material (sealant, coating): particle size 20-50 μm, shell thickness 2-3 μm (balancing dispersibility and response speed). (II) Optimization of preparation process Solvent selection: An aqueous solution of ethanol with a volume fraction of 30%–60% is used to solve the problem of low solubility of methyl red and thymol blue in pure water. Emulsification and polymerization: Particle size is controlled by adjusting the emulsification speed (500–1500 r / min); polymerization temperature is 50–80℃, time is 1–4 h; crosslinking agent dosage is 1%–5% of the wall material mass. Post-processing: Standard sieves are used to control the target particle size, and vacuum drying (40-70℃) is performed to avoid high temperature damage to the indicator activity.

[0005] Beneficial effects Compared with the prior art, the beneficial effects of the present invention are as follows: High versatility: Through a design that combines "diversified wall materials and adaptable particle size / shell thickness," it is compatible with various carriers such as sealants, coatings, packaging films, wound dressings, and concrete. Compared to CN115825056A, which is only applicable to thin-layer materials such as textiles, and CN121228542A, which is only applicable to textile finishing agents, this invention is the first to achieve cross-domain adaptation from industrial structural materials to biomedical materials, reducing R&D and production costs. Excellent adaptability: The wall material is compatible with the carrier environment, and is resistant to organic corrosion, shear, and biocompatibility. The microcapsules are uniformly dispersed in the carrier with a breakage rate of ≤3% (stirring speed ≤800r / min), which is better than the problem of high breakage rate caused by shell brittleness in the existing technology. Precise monitoring: The compound core material covers a pH range of 2–12, with a discernible color gradient; the response time is 5–60 seconds in liquid media and 2–30 minutes in solid carriers, meeting the monitoring needs of different scenarios. Compared to existing single indicator systems (such as CN103169140B which uses natural pigment extracts and has a limited color change range), the compound system of this invention has a wider pH response range; High stability: The core-shell structure isolates the core material from the external environment, with a temperature range of -20 to 80℃, a storage period of ≥12 months (at 25℃ and 60% relative humidity), and an indicator migration rate of ≤1%. Non-interference: The microcapsules and the carrier are physically bonded, without chemical reaction, and do not affect the carrier's curing speed, bonding strength, mechanical properties, biocompatibility and other core indicators; Mature technology: It adopts in-situ polymerization or interfacial polymerization process, which does not require special equipment; the mass production cost is ≤80 yuan / kg for industrial grade and ≤150 yuan / kg for medical grade; the addition amount is only 1% to 5%, which makes it easy to achieve commercial promotion. Detailed Implementation The present invention will be further described in detail below with reference to specific embodiments, but its protection scope is not limited by the embodiments. Example 1 (Sealant Application, Paste Carrier) Microcapsule parameters: Wall material: Polyurethane resin, with 8% polyethylene glycol added as a toughening agent. Particle size: 20–50 μm, shell thickness: 2–3 μm Core material: Methyl red: Bromocresol green: Thymol blue = 2:4:1 (mass ratio) Preparation method: S1. Preparation of core material dispersion: Weigh 20g methyl red, 40g bromocresol green and 10g thymol blue, add 1400mL ethanol aqueous solution (ethanol volume fraction 50%), stir for 30min until completely dissolved to obtain a core material dispersion with a concentration of 5%; S2. Preparation of wall material prepolymer solution: Weigh 140g of polyurethane prepolymer and 11.2g of polyethylene glycol, add 500mL of deionized water, stir and heat to 50℃, add 2.8g of triethylenetetramine (catalyst), keep warm and stir for 40min to obtain wall material prepolymer solution; S3. Emulsification and dispersion: Slowly drip the core material dispersion into the wall material prepolymer solution, add 3g of sodium dodecyl sulfate (emulsifier), and emulsify for 30min at a speed of 1000r / min to form a stable O / W type emulsion; S4. Polymerization and coating: Heat the emulsion to 70°C and keep it at that temperature for 3 hours, stirring continuously at 400 r / min during the process; S5. Post-processing: Cool to room temperature, filter, wash 3 times with deionized water, vacuum dry at 70℃ for 5 hours, and sieve through a 20-50μm standard sieve to obtain the microcapsule product. Application and performance testing: Microcapsules were mixed into silicone sealant at a concentration of 3% by weight, and stirred at 500 rpm. The microcapsule breakage rate was 1.2%. The sealant cured completely, and the bond strength was not significantly different from that of the control group. When immersed in an acidic solution with pH=2, the color turns red after 40 seconds. When immersed in an alkaline solution with pH=12, the color turns blue after 35 seconds. After 12 months of storage at room temperature, the microcapsules showed no migration or discoloration. Example 2 (Application of food packaging film, thin-layer carrier) Microcapsule parameters: Wall material: Gelatin-gum arabic composite (mass ratio 1:1), with 1% glutaraldehyde added as a crosslinking agent. Particle size: 5–10 μm, shell thickness: 1–2 μm Core material: Methyl red: Bromocresol green: Thymol blue = 1:4:1 (mass ratio) Preparation method: S1. Preparation of core material dispersion: Weigh 10g methyl red, 40g bromocresol green and 10g thymol blue, add 1200mL ethanol aqueous solution (ethanol volume fraction 45%), stir for 40min until completely dissolved to obtain a core material dispersion with a concentration of 5%; S2. Preparation of wall material prepolymer solution: Weigh 120g of gelatin-gum arabic composite, add 400mL of deionized water, stir and heat to 45℃, adjust the pH to 3.5 with acetic acid, keep warm and stir for 30min to obtain wall material prepolymer solution; S3. Emulsification and dispersion: Slowly drip the core material dispersion into the wall material prepolymer solution, add 2g of Tween 80 (emulsifier), and emulsify for 20min at a speed of 1500r / min to form a stable O / W type emulsion; S4. Polymerization and coating: Add 1.2g glutaraldehyde (25% aqueous solution), heat the emulsion to 50℃, keep it at the temperature for 2h, and stir continuously at 300r / min during the process; S5. Post-processing: Cool to room temperature, filter, wash 3 times with deionized water, vacuum dry at 40℃ for 6 hours, and sieve through a 5-10μm standard sieve to obtain the microcapsule product. Application and performance testing: Microcapsules were mixed into sodium alginate film raw material at a weight of 3% to produce a biodegradable packaging film with a thickness of 0.1 mm. After packaging fresh pork, it was left at room temperature (25℃) for 3 days (when the pork spoils, pH≈6.8). The membrane surface changed from yellow-green to blue-green, with a response time of approximately 8 minutes. After storage at 25°C and 60% relative humidity for 6 months, the indicator migration rate was 0.5%. The difference in tensile strength between the membrane material and the control group is ≤5%. The biocompatibility test meets the GB 4806.1-2016 standard and is non-toxic. Example 3 (Concrete Application, Structural Carrier) Microcapsule parameters: Wall material: urea-formaldehyde resin, with 10% polypropylene glycol added as a toughening agent. Particle size: 60–80 μm, shell thickness: 3–5 μm Core material: Methyl red: Bromocresol green: Thymol blue = 2:5:2 (mass ratio) Preparation method: S1. Preparation of core material dispersion: Weigh 20g methyl red, 50g bromocresol green and 20g thymol blue, add 1800mL ethanol aqueous solution (ethanol volume fraction 55%), stir for 35min until completely dissolved to obtain a core material dispersion with a concentration of 5%; S2. Preparation of wall material prepolymer: Weigh 180g of urea-formaldehyde resin prepolymer and 23.4g of polypropylene glycol, add 600mL of deionized water, stir and heat to 55℃, add 3.6g of sulfuric acid (catalyst), keep warm and stir for 50min to obtain wall material prepolymer; S3. Emulsification and dispersion: The core material dispersion is slowly dripped into the wall material prepolymer solution, 4g of sodium dodecyl sulfate (emulsifier) ​​is added, and emulsification is carried out at 800r / min for 40min to form a stable O / W type emulsion; S4. Polymerization and coating: The emulsion is heated to 75°C and kept at this temperature for 3.5 hours, during which it is continuously stirred at 500 r / min. S5. Post-processing: Cool to room temperature, filter, wash 3 times with deionized water, vacuum dry at 60℃ for 6 hours, and sieve through a 60-80μm standard sieve to obtain the microcapsule product. Application and performance testing: The microcapsules were mixed into C30 concrete raw materials at a concentration of 4% by weight, with a stirring speed of 800 rpm and a stirring time of 30 minutes. The microcapsule breakage rate was 1.8%. A 100mm×100mm×100mm concrete specimen was prepared, with a compressive strength of 32.2MPa, which was not significantly different from the control group (33.0MPa). The test block was immersed in a sulfuric acid solution with a pH of 2. After 4 hours, the eroded areas on the surface of the test block showed red markings. The test block was immersed in a sodium hydroxide solution with pH=12, and a blue mark appeared after 3.5 hours. Example 4 (Application of wound dressings, biomedical carrier) Microcapsule parameters: Wall material: Sodium alginate-chitosan complex (mass ratio 1:1), with 5% chitosan added as a toughening agent. Particle size: 10–20 μm, shell thickness: 1–2 μm Core material: Methyl red: Bromocresol green: Thymol blue = 1:3:1 (mass ratio) Preparation method: S1. Preparation of core material dispersion: Weigh 10g methyl red, 30g bromocresol green and 10g thymol blue, add 1000mL ethanol aqueous solution (ethanol volume fraction 40%), stir for 30min until completely dissolved to obtain a core material dispersion with a concentration of 5%; S2. Preparation of wall material prepolymer solution: Weigh 100g sodium alginate and 100g chitosan, add 600mL deionized water, adjust the pH to 4.0 with acetic acid, stir and heat to 40℃, keep warm and stir for 30min to obtain wall material prepolymer solution; S3. Emulsification and dispersion: Slowly drip the core material dispersion into the wall material prepolymer solution, add 2g of Tween 80 (emulsifier), and emulsify for 25min at a speed of 1200r / min to form a stable O / W type emulsion; S4. Polymerization and coating: Add 2g of diethylenetriamine, heat the emulsion to 50℃, keep it at this temperature for 2h, and stir continuously at 350r / min during the process; S5. Post-processing: Cool to room temperature, filter, wash 3 times with deionized water, vacuum dry at 50℃ for 5 hours, and sieve through a 10-20μm standard sieve to obtain the microcapsule product. Application and performance testing: Microcapsules were mixed into hydrocolloid dressing at a weight fraction of 2% to prepare a wound dressing with a thickness of 2 mm. When simulated infection exudate (pH≈8.0) comes into contact with the dressing, the surface of the dressing turns blue-green after about 12 minutes. Biocompatibility testing was conducted according to GB / T 16886.5-2017, and the cytotoxicity level was Grade 1 (no cytotoxicity). The skin irritation test result was non-irritating. After storage at 25℃ and 60% relative humidity for 12 months, the microcapsule structure remained intact without any rupture. Comparative Example 1 (without toughening agent) The wall material is polyurethane resin, without the addition of polyethylene glycol toughening agent, otherwise the same as in Example 1. Results: Under a stirring speed of 500 r / min, the microcapsule breakage rate increased from 1.2% to 7.5%, and the shell brittleness was significantly increased. Comparative Example 2 (pure water solvent) The core material is dissolved directly in pure water (without ethanol), and the rest is the same as in Example 2. Results: Thymol blue could not be completely dissolved, the core material dispersion was turbid, the particle size distribution after emulsification was uneven (10–80 μm), and the yield was <60%. Comparative Example 3 (Single Indicator) The core material uses only thymol blue (i.e., methyl red:bromocresol green:thymol blue = 0:0:1), and the rest is the same as in Example 1. Results: Color was only observed in the pH ranges of 1.2–2.8 and 8.0–9.6, with no color change in the pH range of 3–7, failing to meet the requirements for wide-range pH monitoring.

[0006] Supplementary explanation of specific implementation methods The core material ratio can be finely adjusted according to specific monitoring needs. As long as the mass ratio of methyl red, bromocresol green and thymol blue is within the range of (1~3):(2~5):(1~2), segmented colorimetric identification within the pH range of 2~12 can be achieved. The amount of toughening agent added to the wall material can be adjusted according to the stirring intensity of the carrier. When the stirring speed is high, the proportion of toughening agent can be appropriately increased (not exceeding 10%) to reduce the microcapsule breakage rate. During the preparation process, the emulsification speed is negatively correlated with the particle size: the higher the speed, the smaller the particle size; the higher the polymerization temperature, the faster the shell polymerization rate, but it needs to be controlled within the range of 50 to 80°C to avoid high temperature damaging the indicator activity; The scope of protection of this invention is limited to microcapsules employing the core-shell structure, wall material selection, preparation process, and particle size / shell thickness matching principles disclosed in this invention; the application carrier must meet the requirement of being able to bind microcapsules through physical blending, coating, loading, or immersion, and must not exceed the temperature resistance (-20~80℃) and pH response (2~12) range disclosed in this invention.

[0007] Prior art comparison and novelty description A search revealed that the prior art most similar to this invention includes: CN115825056A (Wide-range pH-changing nanocapsules): Utilizes a compound of thymol blue, bromocresol green, and bromocresol violet, with a particle size of 150-180 nm. The differences are: (1) The particle size is nanoscale (150-180 nm), while that of this invention is micrometer-scale (5-100 μm), suitable for different scenarios; (2) The wall material system is different, and this invention provides diversified wall material selection schemes for different carriers; (3) It does not involve the adaptation application with industrial carriers such as concrete and sealant. CN121228542A (Microcapsule Emulsion with pH Indication Function): Employs a polyurethane-polyurea-polyacrylate hybrid shell. The differences are: (1) It only involves a single application scenario of textile finishing agents; (2) It does not provide a particle size and shell thickness adaptation scheme for different carrier types; (3) It does not use a compound indicator system. CN103169140B (Edible Microcapsules for Indicating Probiotic Activity): Uses natural pigment extracts as indicators. The differences are: (1) the color change range is limited, and the pH response range of the compound system of this invention is not as wide; (2) it is mainly used for probiotic activity indication and does not involve industrial carrier applications. US 8,101,209 B2 (pH-responsive microcapsule drug release system): uses Eudragit® L as a pH-sensitive polymer for controlled drug release. The differences are: (1) the purpose is drug sustained release rather than pH monitoring and color development; (2) it does not contain a pH indicator core material; (3) the particle size is 200-800 μm, which is larger than that of this invention. In summary, no existing technology has yet produced a pH-responsive microcapsule that simultaneously possesses the following technical features: (1) a wide range of pH color development achieved by combining methyl red, bromocresol green, and thymol blue; (2) wall material selection and particle size / shell thickness matching schemes for different carrier types (industrial / medical, thin-layer / structural / paste); and (3) shear resistance, low breakage rate, and biocompatibility. This invention is indeed the first of its kind and possesses novelty and inventiveness. Attached Figure Description

[0008] Figure 1 Example 1: Scanning electron microscope image of the microcapsule (scale bar 10 μm).

Claims

1. A pH-responsive microcapsule, characterized in that, The product includes a core material and a wall material; the core material is one or more of methyl red, bromocresol green, and thymol blue; the wall material is selected from urea-formaldehyde resin, polyurethane resin, gelatin-gum arabic complex, and sodium alginate-chitosan complex; the microcapsules have a particle size of 5–100 μm and a shell thickness of 1–5 μm; the microcapsules can produce a visible color change within the pH range of 2–12.

2. The microcapsule according to claim 1, characterized in that, The core material is a compound of methyl red, bromocresol green, and thymol blue in a mass ratio of (1-3):(2-5):(1-2), used for segmented colorimetric identification within the pH range of 2-12; wherein, it is red at pH 2-3, orange-yellow at pH 4-5, yellow-green at pH 6-7, blue-green at pH 8-9, and blue-purple at pH 10-12.

3. The microcapsule according to claim 1, characterized in that, When the wall material is a gelatin-gum arabic composite, it is cross-linked and cured using glutaraldehyde or transglutaminase; when the wall material is a urea-formaldehyde resin or a polyurethane resin, a toughening agent with a mass fraction of 5% to 10% is added, wherein the toughening agent is polyethylene glycol or polypropylene glycol.

4. The microcapsule according to claim 1, characterized in that, The microcapsules have a response time of 5–60 seconds in liquid media and 2–30 minutes in solid or semi-solid carriers; the breakage rate of the microcapsules is ≤3% (under stirring speed ≤800 r / min); the temperature resistance range of the microcapsules is -20 to 80℃, and the storage period is ≥12 months (under 25℃ and 60% relative humidity).

5. A method for preparing the microcapsules according to claim 1, characterized in that, Includes the following steps: S1: Dissolve the core material in an aqueous ethanol solution with a volume fraction of 30% to 60% to obtain a core material dispersion; S2: Dissolve the wall material raw material in deionized water and adjust the pH to 2.5-4.5 to obtain the wall material prepolymer solution; S3: Add the core material dispersion dropwise into the wall material prepolymer solution at an emulsification speed of 500-1500 r / min, add an emulsifier to form an O / W type emulsion; S4: Add a crosslinking agent and react at 50-80℃ for 1-4 hours; S5: Cool, wash, vacuum dry, and sieve to obtain the microcapsule product.

6. The preparation method according to claim 5, characterized in that, The crosslinking agent is one of glutaraldehyde, formaldehyde, triethylenetetramine, or diethylenetriamine; the emulsifier is sodium dodecyl sulfate or Tween 80.

7. The application of the microcapsules according to claim 1 in the preparation of pH monitoring materials, characterized in that, The materials include sealants, coatings, packaging films, wound dressings, or concrete, and the microcapsules are added to the materials at a mass fraction of 1% to 5%.

Images