High-stability anti-allergic collagen-chamomile active component hydrogel as well as large-scale preparation method and application thereof

Abstract

The invention relates to a high-stability anti-allergic collagen-chamomile active component hydrogel as well as a large-scale treatment method and application thereof. Chamomile is used as a raw material, and a method of combining various chemical extraction and separation drying extraction technologies is innovatively and intensively combined. The preparation method comprises the following steps: sequentially preparing a chamomile water-phase component with relatively high sugar extraction rate and relatively high oxidation resistance, a chamomile ethanol-phase component with relatively high total flavone content and relatively high tyrosinase inhibition activity, and a chamomile volatile component which is relatively comprehensive in component, complete in main component, clear in symbolic efficient anti-allergic compound (matricariazulene) and excellent in anti-allergic effect; furthermore, macromolecular collagen is prepared by taking ocean / freshwater fish forehead scales as raw materials, and is purified by anion exchange chromatography / resin; and homogenizing and emulsifying the collagen and chamomile active components (a chamomile water-phase component, a chamomile ethanol-phase component and a chamomile volatile component) to obtain the high-stability anti-allergic collagen-chamomile active component hydrogel suitable for cosmetics.

Description

Technical Field

[0001] This invention relates to a highly stable, anti-allergic collagen-chamomile active ingredient hydrogel, its large-scale processing method and application, involving chemical extraction, separation and purification and homogenization emulsification technology, and belongs to the field of cosmetics. Background Technology

[0002] Chamomile, an annual herb belonging to the genus *Chamomile* in the family Asteraceae, is recorded in the *Illustrated Handbook of Chinese Medicinal Plants* as having the effects of clearing heat and detoxifying, relieving cough and asthma, and dispelling wind and dampness. It is mainly used to treat colds with fever, sore throat, cough and asthma due to lung heat, swelling and pain from heat-related arthralgia, and sores. Chamomile essential oil, extracted from chamomile, is also frequently used to inhibit skin inflammation, promote wound healing, repair skin lacerations, and treat nerve pain. Chamomile is an aromatic plant known to people for a long time and is widely used in Europe, the United States, and Japan. Chamomile-based health products have significant moisturizing, hydrating, and pore-tightening effects; at the same time, due to its various medicinal properties, it has been used as an ingredient in medicated cosmetics.

[0003] Chamomile has excellent soothing and repairing properties for sensitive skin, reducing fine lines and redness, and evening out skin tone. Rich in flavonoids, it possesses antioxidant, anti-angiogenic, anti-inflammatory, anti-allergic, and antiviral effects, making it suitable for use in high-end anti-sensitivity skincare products. Applying a chamomile compress with cotton pads gently replenishes moisture, soothes the skin, and has a soothing effect on itchy skin.

[0004] Currently, both domestic and international patents and Chinese and English literature contain numerous reports on the extraction of single components from chamomile raw materials, such as chamomile polysaccharides (CN201910716078.6), total chamomile flavonoids (CN202310641172.6, CN202410642029.3, CN202211521873.8), or chamomile essential oil (CN202210720959.7), but there are relatively few reports on the comprehensive utilization of multiple active ingredients in chamomile raw materials.

[0005] The comprehensive utilization of multiple active ingredients in chamomile raw materials cannot be achieved simply by replicating and adding existing technologies. Instead, it requires an intensive, combined innovation: keenly grasping the differences in the properties of various components / ingredients, creatively combining various extraction, separation, and drying methods to form a concise and coherent process flow, achieving the sequential and efficient extraction of chamomile's aqueous phase, ethanolic phase, and volatile components. Therefore, this patented technology undoubtedly possesses significant scientific value and practical implications.

[0006] Furthermore, according to literature reports, among the various active components of chamomile, chamomile essential oil (the volatile component of chamomile) has the best calming effect. It can relieve anxiety, tension, anger, and fear, making people relaxed, patient, and peaceful, reducing worry, calming the mind, and also greatly helping to treat insomnia. In terms of skin care, chamomile essential oil can soothe burns, blisters, inflamed wounds, ulcers, and boils; help improve eczema, acne, herpes, psoriasis, hypersensitive skin, and general allergies; soothe broken capillaries, improve elasticity, and is particularly effective for dry, itchy, and sensitive skin. It can reduce swelling and strengthen tissues. Therefore, chamomile essential oil is an excellent skin purifying and care product.

[0007] However, chamomile essential oil contains volatile components such as azulene, α-bisabolol, farnesene, and bisabolol, causing its excellent efficacy to gradually diminish over time. This undoubtedly necessitates an efficient and feasible technology to ensure the stability of the efficacy of chamomile essential oil (its volatile components). This also demonstrates the advanced and groundbreaking nature of this invention's patented technology. Summary of the Invention

[0008] In view of this, the present invention provides a large-scale preparation method for collagen-chamomile active component hydrogel with flexible production process, wide applicability, obvious anti-allergy effect and good stability, so as to realize the high-value development of marine biological resources and the comprehensive utilization of terrestrial plant resources.

[0009] To solve the above-mentioned technical problems, the technical solution of the present invention is:

[0010] A method for large-scale processing of highly stable, anti-allergic collagen-chamomile active component hydrogels, comprising the following steps:

[0011] (1) Preparation of the aqueous phase component of chamomile

[0012] Chamomile raw materials are dried in a hot air drying oven at 60-80℃ for 2-5 hours. After drying, they are placed in a traditional Chinese medicine pulverizer and pulverized for 5-8 minutes. The pulverized chamomile powder is then added to a reaction vessel, along with a dilute acid solution at 5-15 times its weight. The mixture is stirred and reacted for 2-6 hours at a temperature of 85-100℃ and a pH of 4-5. After the high-temperature dilute acid hydrolysis reaction is completed, the mixture is cooled to room temperature, and the pH is adjusted to 6.5-7.5 with a dilute alkali solution. The mixture is then centrifuged at high speed using a continuous flow centrifuge to obtain the first centrifugation residue and the first centrifugation supernatant. The first centrifugation supernatant is desalted and concentrated using a nanofiltration membrane with a relative molecular weight of 500-200 Da to obtain a chamomile aqueous phase solution with a mass-volume concentration ≥10%. The chamomile aqueous phase solution is then rapidly dried using spray drying technology to obtain chamomile aqueous phase powder. The mass-volume concentrations of the dilute acid solution and the dilute alkali solution are 0.01-0.05%, respectively.

[0013] (2) Preparation of the ethanol phase of chamomile

[0014] The residue from the first centrifugation was placed in a vacuum drying oven and dried at 40–50°C for 2–5 hours at a vacuum degree of -0.06 MPa to -0.1 MPa. After vacuum drying, it was removed and placed in a reaction vessel. Anhydrous ethanol solution of 5–15 times the weight of chamomile powder was added, and the mixture was stirred and reacted for 2–6 hours at a reaction temperature of 70–80°C. After the anhydrous ethanol extraction was completed, the mixture was cooled to room temperature and then centrifuged at high speed using a continuous flow centrifuge to obtain the residue from the second centrifugation and the supernatant from the second centrifugation. The supernatant from the second centrifugation was concentrated by rotary evaporation to obtain the chamomile ethanol phase extract. The rotary evaporation temperature was 30–40°C, and the rotary evaporation vacuum degree was -0.02 MPa to -0.06 MPa.

[0015] (3) Preparation of volatile components of chamomile

[0016] The residue from the second centrifugation was placed in a vacuum drying oven and dried at 30–40°C for 2–5 hours at a vacuum degree of -0.04 MPa to -0.06 MPa. After vacuum drying, it was removed and placed in a supercritical CO2 fluid extractor. The extraction temperature was 35–45°C, the extraction time was 0.5–1 hour, and the extraction pressure was 20–30 MPa. The obtained supercritical extract was dissolved in anhydrous ethanol and filtered through a 1–0.2 μm filter to remove insoluble matter. The filtrate was then concentrated by rotary evaporation to obtain the volatile component extract of chamomile. The rotary evaporation temperature was 30–40°C, and the rotary evaporation vacuum degree was -0.02 MPa to -0.06 MPa.

[0017] (4) Degreasing, decalcification and deodorization of fish scale raw materials

[0018] Fish scale raw materials are put into a reaction vessel, and an alkaline solution of 2 to 10 times the weight of the fish scale raw materials is added. The mixture is stirred for 0.5 to 3 hours to remove impurities such as fat and protein from the fish scales, and then washed with water. Next, an acidic solution of 2 to 10 times the weight of the fish scale raw materials is added, and the mixture is stirred for 0.5 to 12 hours, and then washed with water. Then, an ethanolic solution of 2 to 10 times the weight of the fish scale raw materials is added, and the mixture is stirred for 1 to 6 hours, and then washed with water. The mass-volume concentration of the alkaline solution is 1 to 4%, the mass-volume concentration of the acidic solution is 3 to 8%, and the concentration of the ethanolic solution is 40% to 60%. The pretreatment temperature is controlled between 15 and 30°C.

[0019] (5) Extraction and filtration of macromolecular collagen

[0020] Add 0.5–10 mol / L citric acid as an extractant to the defatted, decalcified, and deodorized fish scale raw material. The weight ratio of raw material to extractant is 1:1 to 1:10. Stir for 2–6 hours, maintaining the extraction temperature at 5–15℃. After extraction, perform freeze centrifugation filtration. The residue obtained from filtration is recovered and the extraction and filtration steps are repeated 0–5 times. The resulting centrifugal supernatants are mixed and collected to obtain the crude extract of macromolecular collagen. The crude extract of macromolecular collagen is purified by membrane separation technology. The crude extract is first filtered with a microfiltration membrane with a pore size of 1–0.2 μm to remove fine residues or possible pyrogens that are not visible to the naked eye. The permeate is then filtered with an ultrafiltration membrane with a pore size of 0.1–0.05 μm or a relative molecular weight of 150 KD–100 KD to remove residual pepsin, small molecule impurities, and inorganic salts. The solution of macromolecular collagen is then concentrated.

[0021] (6) Anion exchange chromatography / resin purification of macromolecular collagen followed by nanofiltration membrane desalting and concentration

[0022] The macromolecular collagen solution was adsorbed using anion exchange chromatography / resin. Then, a buffer solution with pH 2.5–4 containing 0.5%–1.5% sodium chloride was prepared to desorb the macromolecular collagen on the anion exchange chromatography / resin. The resulting macromolecular collagen solution was adjusted to pH 6.5–7.5 with sodium hydroxide solution. Small molecule inorganic salts were then removed using a nanofiltration membrane with a relative molecular weight of 500–200 Da. The solution was then concentrated to obtain a macromolecular collagen solution purified by anion exchange chromatography / resin with a mass-volume concentration ≥2%.

[0023] (7) Preparation of collagen-chamomile active component hydrogel

[0024] Dissolve the chamomile aqueous component powder prepared in step (1) in deionized water to prepare a chamomile aqueous component solution with a mass-volume concentration of 3-15%; dissolve the chamomile ethanol component extract prepared in step (2) in anhydrous ethanol to prepare a chamomile ethanol component solution with a mass-volume concentration of 3-15%; dissolve the chamomile volatile component extract prepared in step (3) in anhydrous ethanol to prepare a chamomile volatile component solution with a mass-volume concentration of 3-15%; dissolve the chamomile volatile component extract prepared in step (3) in anhydrous ethanol to prepare a chamomile volatile component solution with a mass-volume concentration of 3-15%; Chamomile aqueous phase solution, chamomile ethanol phase solution, chamomile volatile component solution, and ion exchange chromatography / resin purified macromolecular collagen solution were added to a reaction vessel at a volume ratio of (0.5–1.5):(0.5–1.5):(0.5–1.5):(2–4) and homogenized and emulsified for 0.5–3 hours at a homogenization speed of 1000–28000 rpm, while stirring to maintain the extraction temperature at 5–25°C; thus obtaining a collagen-chamomile active component hydrogel.

[0025] The chamomile raw material in step (1) is German chamomile (Latin name: Matricaria chamomilia) or Roman chamomile (Latin name: Anthemis nobilis).

[0026] The centrifuges used in steps (1), (2) and (5) are large high-speed refrigerated centrifuges with a speed of 6,000 to 15,000 rpm.

[0027] The alkali used in steps (1) and (4) is sodium bicarbonate, potassium bicarbonate, sodium hydroxide or potassium hydroxide; the acid used in steps (1) and (4) is hydrochloric acid or nitric acid; the ethanol solution used in step (4) can be a solution prepared with edible alcohol or a solution containing ethanol prepared with baijiu, huangjiu or cooking wine.

[0028] The inlet air temperature of the spray dryer used in step (1) is 120-180℃ and the outlet air temperature is 70-95℃; the nanofiltration membrane with a relative molecular weight of 500-200 Da used in steps (1) and (6) has a flow rate of 5-14 cubic meters / hour, a membrane pressure of 0.5-2.5 MPa, and a temperature of 20-50℃; the microfiltration membrane with a pore size of 1-0.2 μm used in step (5) has a flow rate of 100-2000 cubic meters / (hour × square meter), a membrane pressure of 0.1-0.6 MPa, and a temperature of 0-10℃; the ultrafiltration membrane with a pore size of 0.1-0.05 μm or a relative molecular weight of 150 KD-100 KD used in the separation and purification has a flow rate of 100-1200 cubic meters / (hour × square meter), a membrane pressure of 0.1-0.6 MPa, and a temperature of 0-10℃.

[0029] The fish scale raw material in step (4) is marine fish scales or freshwater fish scales.

[0030] The anion exchange chromatography / resin used in step (6) is a preparative chromatography or resin with amino, primary amine, secondary amine, tertiary amine or quaternary amine groups; the buffer solution with a pH of 2.5 to 4 used is disodium hydrogen phosphate-citric acid buffer, citrate-sodium citrate buffer, glycine-hydrochloric acid buffer, phthalic acid-hydrochloric acid buffer, citrate-sodium hydroxide-hydrochloric acid buffer, citrate-sodium citrate buffer, acetic acid-sodium acetate buffer.

[0031] In step (7), the aqueous phase solution of chamomile, the ethanol phase solution of chamomile, the volatile component solution of chamomile, and the macromolecular collagen solution purified by ion exchange chromatography / resin are added to the reaction vessel in a volume ratio of 1:1:1:3.

[0032] The present invention also provides a highly stable anti-allergic collagen-chamomile active component hydrogel prepared according to the above method.

[0033] This invention also provides the application of the prepared collagen-chamomile active component hydrogel in the preparation of cosmetics with anti-allergy (soothing), antioxidant, and tyrosinase-inhibiting (whitening) properties.

[0034] Compared with the prior art, the present invention has the following advantages:

[0035] 1. This invention uses chamomile as raw material and employs a high-temperature dilute acid hydrolysis reaction to prepare the chamomile aqueous phase component. The sugar extraction rate of this method is higher than that of the previous process (Comparative Experiment 1) in preparing chamomile polysaccharides (see...). Figure 4 Furthermore, the antioxidant capacity (iron ion reduction / antioxidant capacity and ABTS antioxidant capacity) of the aqueous chamomile component prepared using the process of this invention is stronger than that of the chamomile polysaccharide prepared by the previous process (Comparative Experiment 1) (see...). Figure 5 and Figure 6 Therefore, the high-temperature dilute acid hydrolysis reaction used in this invention can replace the ultrasonic extraction technology, which is more complex and expensive than in previous literature, thus demonstrating significant progress. Furthermore, unlike the chamomile polysaccharides prepared by previous processes (Comparative Experiment 1), the chamomile aqueous phase component prepared by the high-temperature dilute acid hydrolysis reaction in this invention is a mixture of sugars and proteins / peptides (see Table 1).

[0036] 2. Based on the preparation of the aqueous phase component of chamomile, the present invention uses a simple anhydrous ethanol extraction process to prepare the ethanol phase component of chamomile, which has a higher total flavonoid content than the chamomile extract obtained by macroporous resin purification and preliminary ethanol extraction using the previous process (Comparative Experiment 2) (see...). Figure 8Meanwhile, the ethanol phase of chamomile exhibited stronger tyrosinase-inhibiting activity than the chamomile extract obtained by macroporous resin purification using the previous process (Comparative Experiment 2) and the chamomile extract obtained by preliminary ethanol extraction (see...). Figure 9 Therefore, the method of extracting the aqueous phase of chamomile by high-temperature dilute acid hydrolysis and then extracting the ethanol phase of chamomile by anhydrous ethanol can replace the complex and cumbersome macroporous resin purification process in previous literature (comparative experiment 2).

[0037] 3. Based on the preparation of aqueous and ethanolic components of chamomile, this invention further utilizes supercritical fluid chromatography to extract products that are proven to be volatile components of chamomile with a relatively comprehensive composition, complete main components, a clearly identified and highly effective anti-allergic compound (matricophytin), and excellent anti-allergic efficacy (see Tables 2 and 3). Figure 12 and Figure 13 Therefore, the method of extracting volatile components of chamomile by supercritical fluid chromatography after extracting the aqueous and ethanolic components of chamomile can replace the complex and cumbersome method of combining supercritical fluid chromatography extraction with molecular distillation purification (Comparative Experiment 3) and the bulky and expensive steam distillation extraction technology (Comparative Experiment 4) in previous literature.

[0038] 4. This invention uses fish scales from marine / freshwater fish as raw material to prepare macromolecular collagen. The product, after purification by anion exchange chromatography / resin, retains the typical characteristics of collagen in its amino acid composition (see Tables 4 and 5), and its molecular weight is above 100 kDa (100,000 Daltons) (see Table 5). Figure 14 This can still be referred to as macromolecular collagen; simultaneously, due to the significant increase in the content of nonpolar amino acids in the amino acid composition of macromolecular collagen purified by anion exchange chromatography / resin, the emulsification effect of macromolecular collagen purified by anion exchange chromatography / resin with chamomile active components (chamomile aqueous phase component + chamomile ethanol phase component + chamomile volatile component) and the anti-allergic efficacy of the formed collagen-chamomile active component hydrogel are significantly improved (see...). Figure 15 , Figure 16 and Figure 17 ).

[0039] 5. The anti-allergic effect of the collagen-chamomile active component hydrogel prepared by this invention is significantly better than that of the anti-allergic effects of the various active components of chamomile (aqueous chamomile component, ethanolic chamomile component, and volatile chamomile component) prepared sequentially using the process of this invention (see...). Figure 18Furthermore, the anti-allergic effect of the collagen-chamomile active component hydrogel prepared by the process of the present invention is significantly stronger than the anti-allergic effect of the aqueous phase component of chamomile, the ethanol phase component of chamomile and the volatile component of chamomile combined (see Table 6). The process of the present invention can achieve a good effect of "1+1+1>3".

[0040] 6. The collagen-chamomile active component hydrogel prepared by this invention has a significant advantage in terms of stability of anti-allergic efficacy compared to the volatile components of chamomile; after being exposed for 4 hours, the collagen-chamomile active component hydrogel can still maintain a hyaluronidase inhibition rate of over 55%, demonstrating strong anti-allergic efficacy (see...). Figure 19 and Figure 20 ).

[0041] 7. This invention differs from previous patent literature reports on the extraction of single components from chamomile raw materials, such as chamomile polysaccharides, total chamomile flavonoids, or chamomile essential oil. Instead, it creatively combines various extraction, separation, drying, and extraction methods, taking advantage of the differences in the properties of different components, to form a complete, concise, and coherent process flow (see...). Figure 1 This invention enables the sequential and efficient extraction of chamomile's aqueous, ethanolic, and volatile components. More importantly, the innovative and intensive combination of these extraction, separation, and drying methods allows them to replace previously used, complex, and expensive extraction techniques in the preparation of each active component of chamomile. Therefore, this invention is not a simple replication or superposition of existing technologies, but rather an intensive and innovative combination.

[0042] 8. The method of this invention has a wide range of applications. Whether using German chamomile or Roman chamomile as raw material, it can sequentially prepare chamomile aqueous components with high sugar extraction rate and strong antioxidant capacity, chamomile ethanolic components with high total flavonoid content and strong tyrosinase inhibition activity, and chamomile volatile components with comprehensive composition, complete main components, clear marker and highly effective anti-allergic compound (chamomile azurite), and excellent anti-allergic effects. At the same time, regardless of whether the raw material is marine fish scales or freshwater fish scales, the prepared macromolecular collagen, after purification by anion exchange chromatography / resin, is homogenized and emulsified with chamomile active components (chamomile aqueous components + chamomile ethanolic components + chamomile volatile components) to obtain a highly stable anti-allergic collagen-chamomile active component hydrogel suitable for cosmetics. Attached Figure Description

[0043] Figure 1 This is a process flow diagram for the large-scale preparation of one of the raw materials of this invention: various active components of chamomile (aqueous chamomile components, ethanolic chamomile components, and volatile chamomile components).

[0044] Figure 2 This is a process flow diagram of the method of the present invention: a method for large-scale preparation of collagen-chamomile active component hydrogel.

[0045] Figure 3 The process flow diagram for preparing chamomile polysaccharides is shown in the reference "Optimization of Ultrasonic Extraction Process and Study on Free Radical Scavenging Ability of Chamomile Polysaccharides" in Comparative Experiment 1.

[0046] Figure 4 This is a sugar extraction rate diagram (n=3) of the aqueous phase components of chamomile prepared by the process of this invention. Sample 1 is German chamomile polysaccharide prepared by a previous process (Comparative Experiment 1); Sample 2 is the aqueous phase component of German chamomile prepared by the process of this invention; Sample 3 is Roman chamomile polysaccharide prepared by a previous process (Comparative Experiment 1); Sample 4 is the aqueous phase component of Roman chamomile prepared by the process of this invention. Sugar extraction rate (%) = sugar content of the aqueous phase component of chamomile / weight of chamomile raw material × 100%. The sugar content was determined according to the national food safety standard "Determination of Total Sugar Content in Meat Products" (GB / T 9695.31-2008).

[0047] Figure 5 The results show the iron ion reducing / antioxidant capacity of the aqueous components of chamomile prepared by the process of this invention (determined by FRAP method, n=3). Sample 1 is German chamomile polysaccharide prepared by a previous process (Comparative Experiment 1); Sample 2 is the aqueous component of German chamomile prepared by the process of this invention; Sample 3 is Roman chamomile polysaccharide prepared by a previous process (Comparative Experiment 1); and Sample 4 is the aqueous component of Roman chamomile prepared by the process of this invention.

[0048] Figure 6 The results show the ABTS antioxidant capacity of the aqueous components of chamomile prepared by the process of this invention (measured by ABTS method, n=3). Sample 1 is German chamomile polysaccharide prepared by a previous process (Comparative Experiment 1); Sample 2 is the aqueous component of German chamomile prepared by the process of this invention; Sample 3 is Roman chamomile polysaccharide prepared by a previous process (Comparative Experiment 1); and Sample 4 is the aqueous component of Roman chamomile prepared by the process of this invention.

[0049] Figure 7 The process flow diagram for the stepwise preparation of chamomile extract obtained from preliminary alcohol extraction and chamomile extract obtained from macroporous resin purification is shown in reference 2, "Study on process conditions for purification of total flavonoids in chamomile using macroporous resin".

[0050] Figure 8This is a graph showing the total flavonoid content in the ethanol phase of chamomile prepared by the process of this invention (n=3). Sample 1 is German chamomile extract obtained by preliminary ethanol extraction using a previous process (Comparative Experiment 2); Sample 2 is German chamomile extract obtained by macroporous resin purification using a previous process (Comparative Experiment 2); Sample 3 is the ethanol phase of German chamomile prepared by the process of this invention; Sample 4 is Roman chamomile extract obtained by preliminary ethanol extraction using a previous process (Comparative Experiment 2); Sample 5 is Roman chamomile extract obtained by macroporous resin purification using a previous process (Comparative Experiment 2); and Sample 6 is the ethanol phase of Roman chamomile prepared by the process of this invention. The method for detecting the total flavonoid content refers to the People's Republic of China Entry-Exit Inspection and Quarantine Industry Standard "Determination of Total Flavonoids in Exported Food" (SN / T 4592-2016).

[0051] Figure 9 This is a graph showing the experimental results (n=3) of the inhibition of tyrosinase activity by the ethanol phase component of chamomile prepared by the process of this invention. Sample 1 is German chamomile extract obtained by preliminary ethanol extraction using a previous process (Comparative Experiment 2); Sample 2 is German chamomile extract obtained by macroporous resin purification using a previous process (Comparative Experiment 2); Sample 3 is the ethanol phase component of German chamomile prepared by the process of this invention; Sample 4 is Roman chamomile extract obtained by preliminary ethanol extraction using a previous process (Comparative Experiment 2); Sample 5 is Roman chamomile extract obtained by macroporous resin purification using a previous process (Comparative Experiment 2); and Sample 6 is the ethanol phase component of Roman chamomile prepared by the process of this invention. The detection method for the tyrosinase activity inhibition rate refers to the Shanghai Daily Chemical Industry Association group standard "Cosmetics - Test Method for Tyrosinase Activity Inhibition" (T / SHRH 015-2018).

[0052] Figure 10 The reference for Comparative Experiment 3, "Study on Supercritical CO2 Extraction Process of Chamomile Essential Oil", is a process flow diagram for preparing chamomile essential oil.

[0053] Figure 11 This is the process flow diagram for preparing chamomile essential oil, as referenced in Comparative Experiment 4, "Analysis of Content and Components of Roman Chamomile Essential Oil".

[0054] Figure 12This is a gas chromatography / time-of-flight mass spectrometry (GC-TOF / MS) total ion current chromatogram of the volatile components of chamomile prepared according to this invention (1—GC-TOF / MS total ion current chromatogram of volatile components of Roman chamomile; 2—GC-TOF / MS total ion current chromatogram of volatile components of German chamomile). Gas chromatography conditions: RXi-5Sil MS column (60m × 0.25mm × 0.25μm), helium carrier gas, flow rate: 1.0mL / min; Mass spectrometry conditions: electron impact ionization (EI) source, ionization energy: 70eV; ion source temperature: 200℃; transfer line temperature: 250℃; scan range (m / z): 40~450, acquisition rate 10spec / s; mass spectrometry search libraries: Wiley9N library, Nist08 library. The experimental data were qualitatively analyzed by comparing the retention index in the ESO essential oil database.

[0055] Figure 13 This is a graph showing the anti-allergic efficacy of the volatile components of chamomile prepared according to the present invention (n=3). Among them, sample 1 is German chamomile essential oil prepared by a previous process (comparative experiment 3); sample 2 is the volatile component of German chamomile prepared by the process of the present invention; sample 3 is Roman chamomile essential oil prepared by a previous process (comparative experiment 4); and sample 4 is the volatile component of Roman chamomile prepared by the process of the present invention.

[0056] Figure 14 These are gel chromatograms of macromolecular collagen before and after anion exchange chromatography / resin purification (1 – macromolecular collagen from sea bass before anion exchange chromatography / resin purification; 2 – macromolecular collagen from sea bass after anion exchange chromatography / resin purification; 3 – macromolecular collagen from carp before anion exchange chromatography / resin purification; 4 – macromolecular collagen from carp after anion exchange chromatography / resin purification). Chromatographic conditions: SuperdexIncrease 200 gel column, mobile phase: 50 mM phosphate buffer (pH = 6.8) + 150 mM sodium chloride, flow rate: 0.5 mL / min, wavelength: 220 nm.

[0057] Figure 15 This is a graph (n=3) showing the effect of the anion exchange chromatography / resin purification process of this invention on the emulsification effect of collagen-German chamomile active component hydrogel. Sample 1 is a sea bass collagen (purified by anion exchange chromatography / resin)-German chamomile active component hydrogel; Sample 2 is a sea bass collagen (not purified by anion exchange chromatography / resin)-German chamomile active component hydrogel; Sample 3 is a carp collagen (purified by anion exchange chromatography / resin)-German chamomile active component hydrogel; and Sample 4 is a carp collagen (not purified by anion exchange chromatography / resin)-German chamomile active component hydrogel.

[0058] Figure 16 This is a graph showing the effect of the anion exchange chromatography / resin purification process of the present invention on the emulsification effect of collagen-Roman chamomile active component hydrogel (n=3). Sample 2 is a sea bass collagen (purified by anion exchange chromatography / resin)-Roman chamomile active component hydrogel; Sample 3 is a sea bass collagen (not purified by anion exchange chromatography / resin)-Roman chamomile active component hydrogel; Sample 4 is a carp collagen (not purified by anion exchange chromatography / resin)-Roman chamomile active component hydrogel.

[0059] Figure 17 This is a graph showing the effect of the anion exchange chromatography / resin purification process of the present invention on the anti-allergic efficacy of collagen-chamomile active component hydrogel (n=3). Among them, Sample 1 is a hydrogel of sea bass collagen (purified by anion exchange chromatography / resin) - German chamomile active component; Sample 2 is a hydrogel of sea bass collagen (not purified by anion exchange chromatography / resin) - German chamomile active component; Sample 3 is a hydrogel of carp collagen (purified by anion exchange chromatography / resin) - German chamomile active component; Sample 4 is a hydrogel of carp collagen (not purified by anion exchange chromatography / resin) - German chamomile active component; Sample 5 is a hydrogel of sea bass collagen (purified by anion exchange chromatography / resin) - Roman chamomile active component; Sample 6 is a hydrogel of sea bass collagen (not purified by anion exchange chromatography / resin) - Roman chamomile active component; Sample 7 is a hydrogel of carp collagen (purified by anion exchange chromatography / resin) - Roman chamomile active component; and Sample 8 is a hydrogel of carp collagen (not purified by anion exchange chromatography / resin) - Roman chamomile active component.

[0060] Figure 18 This is a diagram showing the anti-allergic efficacy of the various active components of chamomile (aqueous chamomile, ethanolic chamomile, and volatile chamomile) prepared by this invention, as well as the collagen-chamomile active component hydrogel (sample 1 - German chamomile aqueous phase; sample 2 - German chamomile ethanolic phase; sample 3 - German chamomile volatile components; sample 4 - sea bass collagen-German chamomile active component hydrogel; sample 5 - carp collagen-German chamomile active component hydrogel; sample 6 - Roman chamomile aqueous phase; sample 7 - Roman chamomile ethanolic phase; sample 8 - Roman chamomile volatile components; sample 9 - sea bass collagen-Roman chamomile active component hydrogel; sample 10 - carp collagen-Roman chamomile active component hydrogel) (n=3).

[0061] Figure 19The diagram shows the highly stable anti-allergic efficacy of the collagen-German chamomile active component hydrogel prepared by this invention (1 - sea bass collagen-German chamomile active component hydrogel; 2 - carp collagen-German chamomile active component hydrogel; 3 - volatile components of German chamomile) (n=3).

[0062] Figure 20 The diagram shows the highly stable anti-allergic efficacy of the collagen-Roman chamomile active component hydrogel prepared by this invention (1 - sea bass collagen-Roman chamomile active component hydrogel; 2 - carp collagen-Roman chamomile active component hydrogel; 3 - Roman chamomile volatile component) (n=3).

[0063] exist Figure 19 and Figure 20 In this study, the collagen-German / Roman chamomile active component hydrogel and the German / Roman chamomile volatile component were exposed to a temperature of 25°C and a humidity of 50%. Their hyaluronidase inhibition rates were measured at 0, 0.5, 1, 1.5, 2, 3 and 4 hours after the start of the experiment.

[0064] exist Figure 13 , Figure 17 , Figure 18 , Figure 19 and Figure 20 In this study, the higher the hyaluronidase inhibition rate of the sample (chamomile aqueous phase component, chamomile ethanol phase component, chamomile volatile component, and collagen-chamomile active component hydrogel), the stronger its anti-allergic effect. The anti-allergic efficacy was detected using the Elson-Morgan method, as described in the following literature:

[0065] [1]Kawasaki,M.,Toyoda,M.,Teshima,R.,Sawada,JI,Hayashi,T.,&Arisawa,M.,et al.(1994).In vitro antiallergic activity of flavonoids in histaminerelease assay using rat basophilic leukemia(RBl-2H3)cells.Journal of the FoodHygienic Society of Japan(Shokuhin Eiseigaku Zasshi),35(5),497-503_1.

[0066] [2] Wei Baoyao, Gao Chenghai, Teng Jianwen. Study on anti-allergic components in Guangxi sweet tea [J]. Food Science and Technology, 2006, 31(5):4. [3] Li Wanyi. Study on anti-allergic function of Yunnan tea, sweet tea and perilla [D]. Southwest University; Southwest Agricultural University, 2001. Detailed Implementation

[0067] The present invention will now be described in further detail with reference to the accompanying drawings and specific embodiments.

[0068] Example 1:

[0069] A method for large-scale processing of highly stable, anti-allergic collagen-chamomile active component hydrogels, comprising the following steps:

[0070] (1) Preparation of the aqueous phase component of German chamomile

[0071] German chamomile raw materials were dried in a hot air drying oven at 70℃ for 2 hours. After drying, they were removed and placed in a traditional Chinese medicine pulverizer for 5 minutes. The pulverized German chamomile powder was then added to a reaction vessel, along with a dilute hydrochloric acid solution at 10 times its weight. The mixture was stirred and reacted for 4 hours at 90℃ and pH 4.0. After the high-temperature dilute acid hydrolysis reaction was completed, the mixture was cooled to room temperature, and the pH was adjusted to 7.0 with dilute sodium hydroxide solution. The mixture was then centrifuged at 14,000 rpm using a continuous flow centrifuge to obtain the first centrifugation residue and the first centrifugation supernatant. The supernatant from the first centrifugation was concentrated by desalination using a nanofiltration membrane with a relative molecular weight of 500 Da to obtain a German chamomile aqueous solution with a mass-volume concentration of 12.5%. The membrane pressure was 2.10 MPa, the flow rate was 10 cubic meters per hour per square meter, and the temperature was 35°C. Then, the German chamomile aqueous solution was rapidly dried using spray drying technology to obtain German chamomile aqueous powder. The inlet air temperature of the spray dryer was 160°C, and the outlet air temperature was 84°C. The mass-volume concentrations of the dilute hydrochloric acid solution and the dilute sodium hydroxide solution were both 0.04%.

[0072] (2) Preparation of the ethanol phase component of German chamomile

[0073] The residue from the first centrifugation was dried in a vacuum drying oven at 40°C for 5 hours under a vacuum of -0.1 MPa. After vacuum drying, it was removed and placed in a reaction vessel. Anhydrous ethanol solution at 10 times the weight of German chamomile powder was added, and the mixture was stirred and reacted for 3 hours at 75°C. After the anhydrous ethanol extraction was completed, the mixture was cooled to room temperature and then centrifuged at 12,500 rpm using a continuous flow centrifuge to obtain the residue from the second centrifugation and the supernatant from the second centrifugation. The supernatant from the second centrifugation was concentrated by rotary evaporation to obtain the ethanol phase extract of German chamomile. The rotary evaporation temperature was 35°C, and the vacuum degree was -0.04 MPa.

[0074] (3) Preparation of volatile components of German chamomile

[0075] The residue from the second centrifugation was placed in a vacuum drying oven and dried at 35°C for 2 hours with a vacuum degree of -0.04 MPa. After vacuum drying, it was taken out and placed in a supercritical CO2 fluid extractor. The extraction temperature was 30°C, the extraction time was 1 hour, and the extraction pressure was 25 MPa. The obtained supercritical extract was dissolved in anhydrous ethanol and filtered through a 0.45 μm filter to remove insoluble matter. The filtrate was then concentrated by rotary evaporation to obtain the volatile component extract of German chamomile. The rotary evaporation temperature was 35°C and the rotary evaporation vacuum degree was -0.04 MPa.

[0076] (4) Degreasing, decalcification and deodorization of sea bass scales

[0077] Sea bass scales were placed in a reaction vessel, and a sodium bicarbonate solution at 5 times the weight of the sea bass scales was added. The mixture was stirred for 3 hours and then washed with water. Next, a hydrochloric acid solution at 10 times the weight of the sea bass scales was added, and the mixture was stirred for 6 hours and then washed with water. Then, an ethanol solution at 5 times the weight of the sea bass scales was added, and the mixture was stirred for 6 hours and then washed with water. The sodium bicarbonate solution had a mass-volume concentration of 4%, the hydrochloric acid solution had a mass-volume concentration of 5%, and the ethanol solution was a 50% solution prepared with edible alcohol. The pretreatment temperature was controlled at 20°C.

[0078] (5) Extraction and filtration of macromolecular collagen from sea bass

[0079] Add 1 mol / L citric acid as an extraction agent to the defatted, decalcified, and deodorized sea bass scales. The weight ratio of raw material to extraction agent is 1:10. Stir for 6 hours, maintaining the extraction temperature at 10℃. After extraction, perform refrigerated centrifugation filtration. The centrifuge speed is set to 10000 rpm, the centrifugation time is 30 minutes, and the centrifugation temperature is 10℃. The residue obtained from filtration is recovered, and the extraction and filtration steps are repeated 3 times. The resulting supernatants are mixed and collected to obtain the crude extract of sea bass macromolecular collagen. Membrane separation technology is used to purify sea bass macromolecular collagen. The crude extract of molecular collagen was first filtered through a microfiltration membrane with a pore size of 0.2 μm to remove microscopic residues or potential pyrogens invisible to the naked eye. The flow rate of the microfiltration membrane was 1200 cubic meters / (hour × square meter), the membrane pressure was 0.3 MPa, and the temperature was 10 °C. The permeate was then filtered through an ultrafiltration membrane with a pore size of 0.05 μm to remove residual pepsin, small molecule impurities, and inorganic salts. The flow rate of the ultrafiltration membrane was 600 cubic meters / (hour × square meter), the membrane pressure was 0.3 MPa, and the temperature was 10 °C. The resulting solution was concentrated to obtain a macromolecular collagen solution from sea bass.

[0080] (6) Preparative anion exchange chromatography purification of sea bass macromolecular collagen followed by nanofiltration membrane desalting and concentration

[0081] Preparative anion exchange chromatography with primary amine groups was used to adsorb macromolecular collagen from sea bass into a solution. Then, a disodium hydrogen phosphate-citric acid buffer solution (pH 3.0) containing 1.25% sodium chloride was prepared to desorb the macromolecular collagen from the preparative anion exchange chromatography. The resulting macromolecular collagen solution was adjusted to pH 7.5 with sodium hydroxide solution. Small molecule inorganic salts were then removed using a nanofiltration membrane with a relative molecular weight of 500 Da, and the solution was concentrated to obtain a 6% (w / v) preparative anion exchange chromatography-purified macromolecular collagen solution. The membrane pressure was 2.10 MPa, the flow rate was 10 m³ / (h × m²), and the temperature was 35 °C.

[0082] (7) Preparation of sea bass collagen-German chamomile active component hydrogel

[0083] The aqueous component powder of German chamomile prepared in step (1) was dissolved in deionized water to prepare a 6% (w / v) aqueous solution of German chamomile; the ethanolic component extract of German chamomile prepared in step (2) was dissolved in anhydrous ethanol to prepare a 6% (w / v) ethanolic solution of German chamomile; the volatile component extract of German chamomile prepared in step (3) was dissolved in anhydrous ethanol to prepare a 6% (w / v) volatile solution of German chamomile. Chamomile volatile component solution: German chamomile aqueous phase solution, German chamomile ethanol phase solution, German chamomile volatile component solution, and preparative anion exchange chromatography purified sea bass macromolecular collagen solution were added to a reaction vessel at a volume ratio of 1:1:1:3 and homogenized and emulsified for 2.5 hours at a homogenization speed of 15,000 rpm, while stirring to maintain the extraction temperature at 25°C; thus, sea bass collagen-German chamomile active component hydrogel was obtained.

[0084] Example 2:

[0085] A method for large-scale processing of highly stable, anti-allergic collagen-chamomile active component hydrogels, comprising the following steps:

[0086] (1) Preparation of the aqueous phase component of Roman chamomile

[0087] Roman chamomile raw materials were dried in a hot air drying oven at 70℃ for 2 hours. After drying, they were placed in a traditional Chinese medicine pulverizer and pulverized for 8 minutes. The pulverized chamomile powder was then added to a reaction vessel, along with a dilute hydrochloric acid solution at 8 times its weight. The mixture was stirred and reacted for 5 hours at 95℃ and pH 5.0. After the high-temperature dilute acid hydrolysis reaction was completed, the mixture was cooled to room temperature, and the pH was adjusted to 7.5 with dilute potassium hydroxide solution. The mixture was then centrifuged at 10,000 rpm using a continuous flow centrifuge to obtain the first centrifugation residue and the first centrifugation supernatant. The supernatant from the first centrifugation was concentrated using a nanofiltration membrane with a relative molecular weight of 200 Da to obtain a Roman chamomile aqueous solution with a mass-volume concentration of 15%. The flow rate was 6.5 cubic meters per hour per square meter, the membrane pressure was 1.0 MPa, and the temperature was 30°C. The Roman chamomile aqueous solution was then rapidly dried using spray drying technology to obtain Roman chamomile aqueous powder. The inlet air temperature for spray drying was 170°C, and the outlet air temperature was 90°C. The mass-volume concentrations of the dilute hydrochloric acid solution and the dilute potassium hydroxide solution were both 0.01%.

[0088] (2) Preparation of the ethanol phase component of Roman chamomile

[0089] The residue from the first centrifugation was dried in a vacuum drying oven at 50°C for 3 hours with a vacuum degree of -0.08 MPa. After vacuum drying, it was removed and placed in a reaction vessel. Anhydrous ethanol solution with a weight of 12 times that of Roman chamomile powder was added, and the mixture was stirred and reacted for 6 hours at a reaction temperature of 80°C. After the anhydrous ethanol extraction was completed, the mixture was cooled to room temperature and then centrifuged at 8000 rpm using a continuous flow centrifuge to obtain the residue from the second centrifugation and the supernatant from the second centrifugation. The supernatant from the second centrifugation was concentrated by rotary evaporation to obtain the ethanol phase extract of Roman chamomile. The rotary evaporation temperature was 30°C and the vacuum degree of rotary evaporation was -0.02 MPa.

[0090] (3) Preparation of volatile components of Roman chamomile

[0091] The residue from the second centrifugation was placed in a vacuum drying oven and dried at 40°C for 4 hours with a vacuum degree of -0.05 MPa. After vacuum drying, it was taken out and placed in a supercritical CO2 fluid extractor. The extraction temperature was 40°C, the extraction time was 0.75 hours, and the extraction pressure was 30 MPa. The obtained supercritical extract was dissolved in anhydrous ethanol and filtered through a 0.2 μm filter to remove insoluble matter. The filtrate was then concentrated by rotary evaporation to obtain the volatile component extract of Roman chamomile. The rotary evaporation temperature was 30°C and the rotary evaporation vacuum degree was -0.02 MPa.

[0092] (4) Degreasing, decalcifying and deodorizing of carp scales

[0093] Carp scales were added to a reaction vessel, followed by a potassium bicarbonate solution (8 times the weight of the carp scales) and stirred for 1 hour. The mixture was then rinsed with water. Next, a nitric acid solution (5 times the weight of the carp scales) was added and stirred for 3 hours. The mixture was then rinsed with water. Finally, an ethanol solution (10 times the weight of the carp scales) was added and stirred for 4 hours. The mixture was then rinsed with water. The potassium bicarbonate solution had a mass-volume concentration of 3%, the nitric acid solution had a mass-volume concentration of 6%, and the ethanol solution was a 60% concentration prepared from baijiu (Chinese liquor). The pretreatment temperature was controlled at 15°C.

[0094] (5) Extraction and filtration of macromolecular collagen from carp

[0095] Add 2 mol / L citric acid as an extraction agent to the defatted, decalcified, and deodorized carp scales as raw material. The weight ratio of raw material to extraction agent is 1:5. Stir for 2 hours, maintaining the extraction temperature at 15℃. After extraction, perform refrigerated centrifugation filtration. The centrifuge speed is set to 13000 rpm, the centrifugation time is 30 minutes, and the centrifugation temperature is 15℃. The residue obtained from filtration is recovered, and the extraction and filtration steps are repeated 5 times. The resulting supernatants are mixed and collected to obtain the crude extract of carp macromolecular collagen. Membrane separation process. A crude extract of carp macromolecular collagen was purified using a technique involving the following steps: The crude extract was first filtered through a microfiltration membrane with a pore size of 0.4 μm to remove microscopic residues and potential pyrogens invisible to the naked eye. The flow rate was 1800 m³ / (h×m²), the membrane pressure was 0.3 MPa, and the temperature was 5 °C. The permeate was then filtered through an ultrafiltration membrane with a relative molecular weight of 150 KD. The flow rate was 450 m³ / (h×m²), the membrane pressure was 0.2 MPa, and the temperature was 5 °C. The resulting solution was concentrated to obtain a carp macromolecular collagen solution.

[0096] (6) Purification of carp macromolecular collagen by anion exchange resin followed by desalting and concentration by nanofiltration membrane

[0097] A carp macromolecular collagen solution was adsorbed using an amino-containing anion exchange resin. A citrate-sodium citrate buffer solution with pH 2.6 and containing 1.5% sodium chloride was then prepared to desorb the carp macromolecular collagen from the anion exchange resin. The resulting carp macromolecular collagen solution was adjusted to pH 7.0 with sodium hydroxide solution. Small molecule inorganic salts were then removed using a nanofiltration membrane with a relative molecular weight of 200 Da, and the solution was concentrated to obtain a carp macromolecular collagen solution purified by anion exchange resin with a mass-volume concentration of 7.5%. The flow rate was 6.5 m³ / (h×m²), the membrane pressure was 1.0 MPa, and the temperature was 30℃.

[0098] (7) Preparation of carp collagen-Roman chamomile active component hydrogel

[0099] The Roman chamomile aqueous component powder prepared in step (1) was dissolved in deionized water to prepare a chamomile aqueous component solution with a mass-volume concentration of 9%; the Roman chamomile ethanol component extract prepared in step (2) was dissolved in anhydrous ethanol to prepare a Roman chamomile ethanol component solution with a mass-volume concentration of 9%; the Roman chamomile volatile component extract prepared in step (3) was dissolved in anhydrous ethanol to prepare a Roman chamomile volatile component solution with a mass-volume concentration of 9%; the Roman chamomile aqueous component solution, the Roman chamomile ethanol component solution, the Roman chamomile volatile component solution, and the carp macromolecular collagen solution purified by anion exchange resin were added to the reaction vessel in a volume ratio of 1:1:1:3 and homogenized and emulsified for 2 hours at a homogenization speed of 5000 rpm, accompanied by stirring and heat dissipation to maintain the extraction temperature at 20℃; a carp collagen-Roman chamomile active component hydrogel was obtained.

[0100] This invention includes a two-step process, wherein the first step of the process is as follows: Figure 1 As shown, this invention uses chamomile as raw material. First, it is dried and pulverized, then subjected to high-temperature dilute acid hydrolysis and continuous flow centrifugation filtration. The first centrifugation supernatant is processed sequentially using membrane separation and spray drying techniques to obtain the aqueous chamomile component. The remaining first centrifugation residue is first vacuum dried, then extracted with anhydrous ethanol and filtered by continuous flow centrifugation. The second centrifugation supernatant is concentrated by rotary evaporation to obtain the ethanolic chamomile component. The remaining second centrifugation residue is first vacuum dried, then extracted by supercritical fluid chromatography to obtain the volatile chamomile component.

[0101] This invention includes a two-step process, wherein the second step is as follows: Figure 2 As shown, this invention uses marine / freshwater fish scales as raw materials. First, the scales are degreased, decalcified, and deodorized. Then, a low-temperature citric acid extraction process is used, followed by continuous flow centrifugation and membrane separation technology to obtain a macromolecular collagen solution with a content of ≥95%. The macromolecular collagen is then purified by the adsorption and desorption of anion exchange chromatography / resin. Finally, the various active components of chamomile (chamomile aqueous phase, chamomile ethanol phase, and chamomile volatile components) are mixed with the purified macromolecular collagen, and a high-speed homogenization emulsification and embedding technique is used to prepare a collagen-chamomile active component hydrogel.

[0102] like Figure 3 As shown, the method described in the reference "Optimization of Ultrasonic Extraction Process and Study on Free Radical Scavenging Ability of Chamomile Polysaccharides" of this invention uses chamomile as raw material. First, the chamomile is dried and pulverized, then subjected to ultrasonic extraction, precipitated with anhydrous ethanol, and the polysaccharide precipitate is collected by continuous centrifugation. The polysaccharide precipitate is then redissolved, and finally, spray drying is used to obtain solid chamomile polysaccharides. This reference serves as a comparative experiment 1.

[0103] like Figure 4 As shown, regardless of whether German chamomile or Roman chamomile is used as raw material, the sugar extraction rate of the aqueous component of chamomile prepared using the process of this invention is higher than that of chamomile polysaccharides prepared by the previous process (comparative experiment 1); for example Figure 5 and Figure 6 As shown, regardless of whether German chamomile or Roman chamomile is used as the raw material, the antioxidant capacity (iron ion reduction / antioxidant capacity and ABTS antioxidant capacity) of the aqueous chamomile component prepared by the process of this invention is stronger than that of the chamomile polysaccharide prepared by the previous process (comparative experiment 1).

[0104] comprehensive Figure 4 , Figure 5 and Figure 6 The experimental results demonstrate that the high-temperature dilute acid hydrolysis reaction used in this invention can replace the ultrasonic extraction technology, which has a more complex extraction process and more expensive equipment, as described in previous literature, and achieves good preparation results (the aqueous chamomile component prepared by this invention has a high sugar extraction rate and strong antioxidant capacity).

[0105] As shown in Table 1, regardless of whether German chamomile or Roman chamomile is used as the raw material, the aqueous chamomile component prepared using the process of this invention differs significantly in basic composition from the chamomile polysaccharide prepared by the previous process (Comparative Experiment 1). In the aqueous chamomile component, in addition to more than three-quarters (77.75%) of the sugar component, there is also approximately one-fifth (19.71%–19.72%) of the protein / peptide component. This result indicates that the aqueous chamomile component prepared by the high-temperature dilute acid hydrolysis reaction of this invention is a mixture of sugars and proteins / peptides.

[0106] like Figure 7 As shown, the method described in the reference "Study on Process Conditions for Purification of Total Flavonoids from Chamomile using Macroporous Resin" of this invention uses chamomile as raw material. First, it is dried and pulverized, then initially extracted with ethanol and water sequentially. The supernatant is collected by continuous centrifugation and divided into two parts. One part of the supernatant is evaporated by rotary evaporation to obtain the chamomile extract obtained from the initial ethanol extraction. The other part of the supernatant is first purified using macroporous resin, and then evaporated by rotary evaporation to obtain the chamomile extract purified by macroporous resin. This reference serves as a comparative experiment 2.

[0107] like Figure 8As shown, regardless of whether German chamomile or Roman chamomile is used as the raw material, the total flavonoid content in the ethanol phase of chamomile prepared using the process of this invention is slightly higher than that of chamomile extract obtained by macroporous resin purification using the conventional process (Comparative Experiment 2), but significantly higher than that of chamomile extract obtained by preliminary alcohol extraction using the conventional process (Comparative Experiment 2). This result suggests that the high-temperature dilute acid hydrolysis reaction used in the preparation step of the aqueous phase of chamomile in this invention can break the glycosidic bonds of chamomile flavonoid glycosides, thereby removing glycosidic ligands that are easily soluble in water but poorly soluble in ethanol, and obtaining flavonoids or flavonols that are easily soluble in ethanol but poorly soluble in water, thus increasing the total flavonoid content of the ethanol phase of chamomile.

[0108] like Figure 9 As shown, regardless of whether German chamomile or Roman chamomile is used as the raw material, the chamomile ethanol phase component prepared using the process of this invention exhibits slightly stronger tyrosinase inhibitory activity than the chamomile extract obtained by macroporous resin purification using the conventional process (Comparative Experiment 2), but significantly stronger than the chamomile extract obtained by preliminary ethanol extraction using the conventional process (Comparative Experiment 2). This result suggests that the chamomile ethanol phase component prepared by this invention has a higher total flavonoid content, resulting in stronger tyrosinase inhibitory activity.

[0109] comprehensive Figure 8 and Figure 9 The experimental results also prove that the method of extracting the aqueous phase of chamomile by high-temperature dilute acid hydrolysis and then extracting the ethanol phase of chamomile by anhydrous ethanol can replace the complicated and cumbersome macroporous resin purification process in previous literature (comparative experiment 2), and achieve good preparation results (the ethanol phase of chamomile prepared by this invention has a high total flavonoid content and strong tyrosinase inhibitory activity).

[0110] like Figure 10 As shown, the method described in the reference "Research on Supercritical CO2 Extraction Process of Chamomile Essential Oil" of this invention uses chamomile as raw material. The chamomile is first dried and pulverized, then extracted by supercritical fluid chromatography and refined by molecular distillation to obtain chamomile essential oil. This reference serves as a comparative experiment 3.

[0111] like Figure 11 As shown, the method described in the reference "Content and Component Analysis of Roman Chamomile Essential Oil" of this invention uses chamomile as raw material. The chamomile is first dried and pulverized, then extracted by steam distillation, dried by anhydrous sodium sulfate absorption, and filtered through a membrane to obtain chamomile essential oil. This reference serves as a comparative experiment 4.

[0112] like Figure 12As shown in Table 2, a total of 66 volatile compounds were identified in the volatile components of German chamomile prepared using the process of this invention. These included 10 alcohols, 1 acid, 2 heterocyclic compounds, 4 aldehydes, 2 phenols, 11 esters, 5 ketones, 27 alkenes and alkenes, and 4 other compounds. The main components were (E)-β-farnesene, bicyclic geraniol, α-bisabolol oxide B, α-bisabolone oxide, α-bisabolol oxide A, geraniol D, (E)-β-ocimene, chamomile, spartanol, artemisinin, menthol, carvone, and other compounds. Compared to the 72 volatile compounds identified in the reference "Analysis of Volatile Components in German Chamomile Oil by Gas Chromatography-Time-of-Flight Mass Spectrometry", the 66 volatile compounds identified in the volatile components of German chamomile prepared using the process of this invention, although fewer in number, have almost identical main components. In particular, both the volatile components of German chamomile prepared using the process of this invention and the German chamomile essential oil in the reference have the characteristic compounds and highly effective anti-allergic substances unique to chamomile essential oil—matricophytin.

[0113] like Figure 12 As shown in Table 3, a total of 59 volatile compounds were identified in the volatile components of Roman chamomile prepared using the process of this invention. These included 14 alcohols, 2 acids, 2 aldehydes, 29 esters, 4 ketones, and 8 alkenes / alkenes. The main components were butyl isovalerate, butyl tetroxide, (E)-carvone alcohol, isobutyl isobutyrate, isoamyl isobutyrate, carvone, 2-pinene, 2-methylbutyrate-2-dimethylpropyl ester, pantothenic acid lactone, isobutyl tetroxide, myrtol, and 2-methylbutyl acetate. Compared to the 50 volatile compounds identified in the Roman chamomile essential oil prepared from whole flowers in the reference "Analysis of Roman Chamomile Essential Oil Content and Components" (Comparative Experiment 4), the Roman chamomile volatile components prepared using the process of this invention identified a greater number of volatile compounds (59).

[0114] like Figure 13 As shown, the anti-allergic efficacy (indicated by hyaluronidase inhibition rate) of the volatile components of chamomile prepared using the process of this invention, using German chamomile as raw material, is basically the same as that of the German chamomile essential oil prepared by comparative experiment 3 (a method combining supercritical fluid chromatography extraction and molecular distillation purification); however, the anti-allergic efficacy of the volatile components of chamomile prepared using the process of this invention, using Roman chamomile as raw material, is far superior to that of the Roman chamomile essential oil prepared by comparative experiment 4 (steam distillation extraction technology).

[0115] Combine Table 2 and Table 3 Figure 12 and Figure 13The experimental results show that, compared to chamomile essential oil prepared by previous processes (Comparative Experiments 3 and 4), the product prepared using the process of this invention, regardless of whether German or Roman chamomile is used as raw material, is a chamomile volatile component with a more comprehensive composition, complete main components, a clearly identified and highly effective anti-allergic compound (matricophytin), and excellent anti-allergic efficacy. This result indicates that the method of extracting chamomile volatile components by supercritical fluid chromatography after extracting the aqueous and ethanolic phases of chamomile can replace the complex and cumbersome method of combining supercritical fluid chromatography extraction with molecular distillation purification (Comparative Experiment 3) and the large and expensive steam distillation extraction technology (Comparative Experiment 4) used in previous literature, achieving excellent preparation results.

[0116] As shown in Tables 4 and 5, glycine accounts for approximately one-third of the total amino acids in both macromolecular collagen prepared from the scales of marine fish (sea bass as an example) and macromolecular collagen prepared from the scales of freshwater fish (carp as an example), which is a typical characteristic of collagen. Furthermore, glycine still accounts for approximately one-third of the total amino acids in the amino acid composition of both sea bass and carp macromolecular collagen after anion exchange chromatography / resin purification. This result indicates that macromolecular collagen purified by anion exchange chromatography / resin still retains the typical characteristics of collagen. Meanwhile, by comparing the amino acid composition of sea bass macromolecular collagen and carp macromolecular collagen before and after anion exchange chromatography / resin purification, it can be seen that the anion exchange chromatography / resin purification process used in this invention significantly increases the content of nonpolar amino acids (also known as hydrophobic amino acids, including Ala, Val, Met, Ile, Leu, Phe, Pro, and Trp) in both marine fish macromolecular collagen (taking sea bass macromolecular collagen as an example) and freshwater fish macromolecular collagen (taking carp macromolecular collagen as an example).

[0117] like Figure 14 As shown, whether using fish scales from marine fish (e.g., sea bass) or freshwater fish (e.g., carp) as raw materials, the molecular weight of macromolecular collagen from both marine and freshwater fish (e.g., carp macromolecular collagen) before and after anion exchange chromatography / resin purification is above 100 kDa (100,000 Daltons). This result demonstrates that, on the one hand, the anion exchange chromatography / resin purification process used in this invention does not alter the molecular weight distribution of macromolecular collagen; on the other hand, it also proves that both sea bass collagen and carp collagen before and after anion exchange chromatography / resin purification can be considered macromolecular collagen.

[0118] like Figure 15 and Figure 16 As shown, regardless of whether German chamomile or Roman chamomile is used as the raw material, the emulsification effect of the chamomile active component (chamomile aqueous phase component + chamomile ethanol phase component + chamomile volatile component) prepared using the process of this invention with macromolecular collagen from marine fish (taking sea bass macromolecular collagen as an example) or freshwater fish (taking carp macromolecular collagen as an example) after anion exchange chromatography / resin purification is significantly better than its emulsification effect with macromolecular collagen from marine fish (taking sea bass macromolecular collagen as an example) or freshwater fish (taking carp macromolecular collagen as an example) before anion exchange chromatography / resin purification. This result demonstrates the significant advancement of the present invention in using anion exchange chromatography / resin purification technology to treat macromolecular collagen.

[0119] At the same time, such as Figure 15 As shown, the collagen-German chamomile active component hydrogel, prepared using the process of this invention and using German chamomile as raw material, is emulsified with macromolecular collagen from marine fish (taking sea bass macromolecular collagen as an example) or freshwater fish (taking carp macromolecular collagen as an example) purified by anion exchange chromatography / resin to form a special deep blue color. This is because the German chamomile volatile component prepared by this invention contains magnolol (also known as: blue chamomile oil hydrocarbon), which is deep blue in color. Figure 15 The observed phenomena are consistent with the qualitative results of the volatile components of German chamomile in Table 2.

[0120] like Figure 16 As shown, the collagen-Roman chamomile active component hydrogel prepared using the process of this invention (Roman chamomile aqueous phase component + Roman chamomile ethanol phase component + Roman chamomile volatile component) and macromolecular collagen from marine fish (taking sea bass macromolecular collagen as an example) or freshwater fish (taking carp macromolecular collagen as an example) purified by anion exchange chromatography / resin does not appear blue. This is because the Roman chamomile volatile component prepared by this invention does not contain chamomile extract, resulting in a light yellow color for the Roman chamomile volatile component. Figure 16 The observed phenomena are consistent with the qualitative results of the volatile components of Roman chamomile in Table 3.

[0121] like Figure 17As shown, regardless of whether German chamomile or Roman chamomile is used as the raw material, the active chamomile component (chamomile aqueous phase component + chamomile ethanol phase component + chamomile volatile component) prepared using the process of this invention is respectively mixed with macromolecular collagen from marine fish (taking sea bass macromolecular collagen as an example) or macromolecular collagen from freshwater fish (taking carp macromolecular collagen as an example) purified by anion exchange chromatography / resin. The resulting collagen (after anion exchange chromatography / resin purification) is then processed using the high-speed homogenization emulsification and embedding technology of this invention. The anti-allergic efficacy (indicated by hyaluronidase inhibition rate) of the collagen (unpurified by anion exchange chromatography / resin)-chamomile active component hydrogel was consistently superior to that of the collagen (unpurified by anion exchange chromatography / resin)-chamomile active component hydrogel prepared by the high-speed homogenization emulsification and embedding technology of this invention. This result demonstrates the significant advancement of this invention in processing large-molecule collagen using anion exchange chromatography / resin purification technology.

[0122] like Figure 18 As shown, regardless of whether German chamomile or Roman chamomile is used as the raw material, the anti-allergic effects of each active component of chamomile (aqueous chamomile component, ethanolic chamomile component, and volatile chamomile component) prepared sequentially using the process of this invention are significantly weaker than the anti-allergic effects of the collagen-chamomile active component hydrogel prepared using the process of this invention. Furthermore, considering the anti-allergic efficacy data in Table 6, it can be seen that regardless of whether German or Roman chamomile is used as the raw material, the combined results of the hyaluronidase inhibition rates of the aqueous chamomile component, ethanolic chamomile component, and volatile chamomile component (total 1 and total 2) are also lower than the hyaluronidase inhibition rate data of the collagen-chamomile active component hydrogel prepared using the process of this invention. This result demonstrates that the anti-allergic effect of the collagen-chamomile active component hydrogel prepared by the process of this invention is significantly stronger than the combined anti-allergic effects of the aqueous phase of chamomile, the ethanol phase of chamomile, and the volatile components of chamomile. The process of this invention can achieve a good effect of "1+1+1>3".

[0123] like Figure 19 and Figure 20As shown, regardless of whether German chamomile or Roman chamomile is used as the raw material, the hyaluronidase inhibition rate of the volatile components of chamomile prepared using the process of this invention decreases rapidly with increasing exposure time. After 2 hours of exposure, their hyaluronidase inhibition rate is approximately 0, and their anti-allergic effect is almost negligible. However, the hyaluronidase inhibition rate of the collagen-chamomile active component hydrogel prepared using the process of this invention decreases slowly with increasing exposure time. Even after 4 hours of exposure, the collagen-chamomile active component hydrogel prepared using this invention can still maintain a hyaluronidase inhibition rate of over 55%, exhibiting strong anti-allergic efficacy. This result proves that the collagen-chamomile active component hydrogel prepared by this invention has a significant advantage in terms of the stability of its anti-allergic efficacy compared to the volatile components of chamomile. Therefore, the collagen-chamomile active component hydrogel prepared by this invention is a highly stable anti-allergic hydrogel suitable for cosmetics.

[0124] Table 1

[0125]

[0126]

[0127] Note: Table 1 is the basic component analysis table of the aqueous phase of chamomile (n=3). The detection methods for moisture content and ash content are based on the National Food Safety Standard "Determination of Moisture in Food" (GB / T 5009.3-2016); the detection methods for ash content and fat content are based on the National Food Safety Standard "Determination of Fat in Food" (GB / T 5009.4-2016); the detection methods for fat content and protein / peptide content are based on the National Food Safety Standard "Determination of Protein in Food" (GB / T 5009.5-2016); the detection methods for sugar content and sugar content are based on the National Food Safety Standard "Determination of Total Sugar Content in Meat Products" (GB / T 9695.31-2008); other compound content (%) = 100% - moisture content (%) - ash content (%) - fat content (%) - protein / peptide content (%) - sugar content (%).

[0128] Table 2

[0129]

[0130]

[0131] Note: Table 2 presents the qualitative results of the volatile components of German chamomile. The retention index (observed value) was automatically calculated by the Pegasus 4D workstation, while the retention index (reference value) uses data from the ESO essential oil database.

[0132] Table 3

[0133]

[0134]

[0135]

[0136] Note: Table 3 presents the qualitative results of the volatile components of Roman chamomile. The retention index (observed value) was automatically calculated by the Pegasus 4D workstation, while the retention index (referenced value) uses data from the ESO essential oil database.

[0137] Table 4

[0138]

[0139] Note: Table 4 shows the amino acid content (n=3) of the sea bass macromolecular collagen purified by anion exchange chromatography / resin according to the present invention. The nonpolar amino acids (hydrophobic amino acids) are Ala, Val, Met, Ile, Leu, Phe, Pro, and Trp. The detection methods for Ala, Arg, Asp, Glu, Gly, Hlys, His, Hyp, Ile, Leu, Lys, Phe, Pro, Ser, Thr, Tyr, and Val are in accordance with the National Food Safety Standard "Determination of Amino Acids in Food" (GB 5009.124-2016); the detection method for Trp is in accordance with the National Standard of the People's Republic of China "Determination of Amino Acids in Feed" (GB / T 18246—2019); and the detection methods for Cys and Met are in accordance with the National Standard of the People's Republic of China "Determination of Sulfur-Containing Amino Acids in Feed - Ion Exchange Chromatography" (GB / T15399-2018).

[0140] Table 5

[0141]

[0142] Note: Table 5 shows the amino acid content (n=3) of carp macromolecular collagen purified by anion exchange chromatography / resin according to the present invention. Among them, nonpolar amino acids (hydrophobic amino acids) are Ala, Val, Met, Ile, Leu, Phe, Pro, and Trp; the detection methods for Ala, Arg, Asp, Glu, Gly, Hlys, His, Hyp, Ile, Leu, Lys, Phe, Pro, Ser, Thr, Tyr, and Val refer to the National Food Safety Standard "Determination of Amino Acids in Food" (GB 5009.124-2016); the detection method for Trp refers to the National Standard of the People's Republic of China "Determination of Amino Acids in Feed" (GB / T 18246—2019); and the detection methods for Cys and Met refer to the National Standard of the People's Republic of China "Determination of Sulfur-Containing Amino Acids in Feed - Ion Exchange Chromatography" (GB / T 15399-2018).

[0143] Table 6

[0144]

[0145] Note: Table 6 shows the anti-allergic efficacy results (n=3) of each active component of chamomile (aqueous phase of chamomile, ethanol phase of chamomile, and volatile components of chamomile) prepared in this invention, as well as the collagen-chamomile active component hydrogel. Specifically, Total 1 = German chamomile aqueous phase + German chamomile ethanol phase + German chamomile volatile components; Total 2 = Roman chamomile aqueous phase + Roman chamomile ethanol phase + Roman chamomile volatile components.

Claims

1. A method for large-scale processing of a highly stable, anti-allergic collagen-chamomile active component hydrogel, comprising the following steps: (1) Preparation of the aqueous phase component of chamomile Chamomile raw materials are dried in a hot air drying oven at 60-80℃ for 2-5 hours. After drying, they are placed in a traditional Chinese medicine pulverizer and pulverized for 5-8 minutes. The pulverized chamomile powder is then added to a reaction vessel, along with a dilute acid solution at 5-15 times its weight. The mixture is stirred and reacted for 2-6 hours at a temperature of 85-100℃ and a pH of 4.0-5.

0. After the high-temperature dilute acid hydrolysis reaction is completed, the mixture is cooled to room temperature, and the pH is adjusted to 6.5-7.5 with a dilute alkali solution. The mixture is then centrifuged at high speed using a continuous flow centrifuge to obtain the first centrifugation residue and the first centrifugation supernatant. The first centrifugation supernatant is desalted and concentrated using a nanofiltration membrane with a relative molecular weight of 500-200 Da to obtain a chamomile aqueous phase solution with a mass-volume concentration ≥10%. This solution is then rapidly dried using spray drying technology to obtain chamomile aqueous phase powder. The mass-volume concentrations of the dilute acid solution and the dilute alkali solution are 0.01–0.05%, respectively. (2) Preparation of the ethanol phase of chamomile The residue from the first centrifugation was placed in a vacuum drying oven and dried at 40–50°C for 2–5 hours at a vacuum degree of -0.06 MPa to -0.1 MPa. After vacuum drying, it was removed and placed in a reaction vessel. Anhydrous ethanol solution of 5–15 times the weight of chamomile powder was added, and the mixture was stirred and reacted for 2–6 hours at a reaction temperature of 70–80°C. After the anhydrous ethanol extraction was completed, the mixture was cooled to room temperature and then centrifuged at high speed using a continuous flow centrifuge to obtain the residue from the second centrifugation and the supernatant from the second centrifugation. The supernatant from the second centrifugation was concentrated by rotary evaporation to obtain the chamomile ethanol phase extract. The rotary evaporation temperature was 30–40°C, and the rotary evaporation vacuum degree was -0.02 MPa to -0.06 MPa. (3) Preparation of volatile components of chamomile The residue from the second centrifugation was placed in a vacuum drying oven and dried at 30–40°C for 2–5 hours at a vacuum degree of -0.04 MPa to -0.06 MPa. After vacuum drying, it was removed and placed in a supercritical CO2 fluid extractor. The extraction temperature was 35–45°C, the extraction time was 0.5–1 hour, and the extraction pressure was 20–30 MPa. The obtained supercritical extract was dissolved in anhydrous ethanol and filtered through a 1–0.2 μm filter to remove insoluble matter. The filtrate was then concentrated by rotary evaporation to obtain the volatile component extract of chamomile. The rotary evaporation temperature was 30–40°C, and the rotary evaporation vacuum degree was -0.02 MPa to -0.06 MPa. (4) Degreasing, decalcifying and deodorizing of fish scale raw materials Fish scale raw materials are put into a reaction vessel, and an alkaline solution of 2 to 10 times the weight of the fish scale raw materials is added. The mixture is stirred for 0.5 to 3 hours to remove impurities such as fat and protein from the fish scales, and then washed with water. Next, an acidic solution of 2 to 10 times the weight of the fish scale raw materials is added, and the mixture is stirred for 0.5 to 12 hours, and then washed with water. Then, an ethanolic solution of 2 to 10 times the weight of the fish scale raw materials is added, and the mixture is stirred for 1 to 6 hours, and then washed with water. The mass-volume concentration of the alkaline solution is 1 to 4%, the mass-volume concentration of the acidic solution is 3 to 8%, and the concentration of the ethanolic solution is 40% to 60%. The pretreatment temperature is controlled between 15 and 30°C. (5) Extraction and filtration of macromolecular collagen Add 0.5–10 mol / L citric acid as an extractant to the defatted, decalcified, and deodorized fish scale raw material. The weight ratio of raw material to extractant is 1:1 to 1:

10. Stir for 2–6 hours, maintaining the extraction temperature at 5–15℃. After extraction, perform freeze centrifugation filtration. The residue obtained from filtration is recovered and the extraction and filtration steps are repeated 0–5 times. The resulting centrifugal supernatants are mixed and collected to obtain the crude extract of macromolecular collagen. The crude extract of macromolecular collagen is purified by membrane separation technology. The crude extract is first filtered with a microfiltration membrane with a pore size of 1–0.2 μm to remove fine residues or possible pyrogens that are not visible to the naked eye. The permeate is then filtered with an ultrafiltration membrane with a pore size of 0.1–0.05 μm or a relative molecular weight of 150 KD–100 KD to remove residual pepsin, small molecule impurities, and inorganic salts. The solution of macromolecular collagen is then concentrated. (6) Anion exchange chromatography / resin purification of macromolecular collagen followed by nanofiltration desalting and concentration The macromolecular collagen solution was adsorbed using anion exchange chromatography / resin. Then, a buffer solution with pH 2.5–4 containing 0.5%–1.5% sodium chloride was prepared to desorb the macromolecular collagen on the anion exchange chromatography / resin. The resulting macromolecular collagen solution was adjusted to pH 6.5–7.5 with sodium hydroxide solution. Small molecule inorganic salts were then removed using a nanofiltration membrane with a relative molecular weight of 500–200 Da. The solution was then concentrated to obtain a macromolecular collagen solution purified by anion exchange chromatography / resin with a mass-volume concentration ≥5%. (7) Preparation of collagen-chamomile active component hydrogel Dissolve the chamomile aqueous component powder prepared in step (1) in deionized water to prepare a chamomile aqueous component solution with a mass-volume concentration of 3-15%; dissolve the chamomile ethanol component extract prepared in step (2) in anhydrous ethanol to prepare a chamomile ethanol component solution with a mass-volume concentration of 3-15%; dissolve the chamomile volatile component extract prepared in step (3) in anhydrous ethanol to prepare a chamomile volatile component solution with a mass-volume concentration of 3-15%; dissolve the chamomile volatile component extract prepared in step (3) in anhydrous ethanol to prepare a chamomile volatile component solution with a mass-volume concentration of 3-15%; Chamomile aqueous phase solution, chamomile ethanol phase solution, chamomile volatile component solution, and macromolecular collagen solution purified by anion exchange chromatography / resin were added to a reaction vessel at a volume ratio of (0.5–1.5):(0.5–1.5):(0.5–1.5):(2–4). Homogenization and emulsification were carried out for 0.5–3 hours at a homogenization speed of 1000–28000 rpm, accompanied by stirring to maintain the extraction temperature at 5–25°C. A collagen-chamomile active component hydrogel was obtained.

2. The method for large-scale processing of a highly stable, anti-allergic collagen-chamomile active component hydrogel according to claim 1, characterized in that: The chamomile raw material in step (1) is German chamomile (Latin name: Matricaria chamomilia) or Roman chamomile (Latin name: Anthemis nobilis).

3. The method for large-scale processing of a highly stable, anti-allergic collagen-chamomile active component hydrogel according to claim 1, characterized in that: The centrifuges used in steps (1), (2) and (5) are large high-speed refrigerated centrifuges with a speed of 6000 to 15000 rpm.

4. The method for large-scale processing of a highly stable, anti-allergic collagen-chamomile active component hydrogel according to claim 1, characterized in that: The alkali used in steps (1) and (4) is sodium bicarbonate, potassium bicarbonate, sodium hydroxide or potassium hydroxide; the acid used in steps (1) and (4) is hydrochloric acid or nitric acid; the ethanol solution used in step (4) can be a solution prepared with edible alcohol or a solution containing ethanol prepared with baijiu, huangjiu or cooking wine.

5. The method for large-scale processing of a highly stable, anti-allergic collagen-chamomile active component hydrogel according to claim 1, characterized in that: The inlet air temperature of the spray dryer used in step (1) is 120-180℃ and the outlet air temperature is 70-95℃; the nanofiltration membrane with a relative molecular weight of 500-200 Da used in steps (1) and (6) has a flow rate of 5-14 cubic meters / (hour × square meter), a membrane pressure of 0.5-2.5 MPa, and a temperature of 20-50℃; the microfiltration membrane with a pore size of 1-0.2 μm used in step (5) has a flow rate of 100-2000 cubic meters / (hour × square meter), a membrane pressure of 0.1-0.6 MPa, and a temperature of 0-10℃; the ultrafiltration membrane with a pore size of 0.1-0.05 μm or a relative molecular weight of 150 KD-100 KD used in the separation and purification has a flow rate of 100-1200 cubic meters / (hour × square meter), a membrane pressure of 0.1-0.6 MPa, and a temperature of 0-10℃.

6. The method for large-scale processing of a highly stable, anti-allergic collagen-chamomile active component hydrogel according to claim 1, characterized in that: Step (4) The raw material for fish scales is marine fish scales or freshwater fish scales.

7. The method for large-scale processing of a highly stable, anti-allergic collagen-chamomile active component hydrogel according to claim 1, characterized in that: The anion exchange chromatography / resin used in step (6) is a preparative chromatography or resin with amino, primary amine, secondary amine, tertiary amine or quaternary amine groups; the buffer solution with a pH of 2.5 to 4 used is disodium hydrogen phosphate-citric acid buffer, citrate-sodium citrate buffer, glycine-hydrochloric acid buffer, phthalic acid-hydrochloric acid buffer, citrate-sodium hydroxide-hydrochloric acid buffer, citrate-sodium citrate buffer, acetic acid-sodium acetate buffer.

8. According to claim 1, the method for large-scale processing of a highly stable anti-allergic collagen-chamomile active component hydrogel, in step (7), the aqueous phase solution of chamomile, the ethanol phase solution of chamomile, the volatile component solution of chamomile and the macromolecular collagen solution purified by anion exchange chromatography / resin are added to the reaction vessel in a volume ratio of 1:1:1:

3.

9. A collagen-chamomile active component hydrogel prepared by the large-scale preparation method according to any one of claims 1 to 8.

10. The use of the collagen-chamomile active ingredient hydrogel as described in claim 9 in the preparation of cosmetics with anti-allergic, antioxidant, or tyrosinase-inhibiting properties.

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