Nanoscale processing technology for protecting and enhancing efficient active ingredients of curcuma wenyujin

Abstract

The invention discloses a nanoscale processing technology for protecting and enhancing efficient active ingredients of curcuma wenyujin. The nanoscale processing technology comprises the following steps: (1) basic protection treatment; (2) biotransformation treatment; (3) redox regulation and control treatment: treating for 90 seconds at 4 + / -1 DEG C by using a 0.015-0.025% H2O2 solution to carry out oxidative stress micro-stimulation, and adding nano cerium oxide as a redox regulator at the same time; activating treatment is performed for 2 minutes through plasma with the frequency of 13.56 MHz and the power of 80 W; and (4) carrying drugs and coating. In conclusion, the invention has the following beneficial effects: the efficient active ingredient protection and synergistic nano-scale processing technology for curcuma wenyujin reduces the loss of curcuma wenyujin in the treatment process, and can improve the drug effect of curcuma wenyujin in the subsequent use process.

Description

Technical Field

[0001] The invention relates to a processing technology of Curcuma wenyujin, in particular to a nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma wenyujin. Background Art

[0002] As an important variety of traditional Chinese medicinal materials, Curcuma wenyujin mainly has active ingredients including volatile oils, curcuminoid compounds, etc., which have significant effects of promoting blood circulation and removing blood stasis, promoting qi and relieving pain. With the development of modern Chinese medicine industry, higher requirements are put forward for the extraction and utilization efficiency of active ingredients of Curcuma wenyujin. Currently, the processing methods of Curcuma wenyujin on the market mainly include traditional physical crushing, solvent extraction and other processes, which are widely used in industrial production.

[0003] The existing processing technology of Curcuma wenyujin usually adopts the following steps: first, the Curcuma wenyujin is pre-treated by washing and drying; then it is made into powders of different particle sizes by mechanical crushing; finally, its active ingredients are obtained by organic solvent extraction or water extraction. Some processes also use modern technical means such as ultrasonic assisted extraction and microwave extraction to improve the extraction efficiency.

[0004] However, the existing processing technology has significant technical limitations. In the early processing, the heat and shear force generated by mechanical crushing can easily lead to the degradation of heat-sensitive components and the loss of volatile components in Wenyujin. The particles obtained by traditional crushing methods have uneven particle size distribution and large particle size, which limits the release and absorption of active ingredients.

[0005] In the extraction process, conventional solvent extraction methods often require higher temperatures and longer extraction times, which not only aggravates the degradation of active ingredients, but also causes changes in the chemical structure of some unstable ingredients. At the same time, the selectivity of traditional extraction processes is poor, and it is easy to extract some non-target ingredients at the same time, affecting the purity and quality of the product.

[0006] In addition, the product obtained by the existing process has a large particle size and low bioavailability, making it difficult to fully exert the efficacy of Wenyujin. Due to the limitation of particle size, the dissolution rate and absorption degree of the drug components in the human body are affected, and the ideal therapeutic effect cannot be achieved.

[0007] It is particularly noteworthy that the existing technology mainly focuses on how to reduce the loss during the processing, but rarely considers how to improve the biological activity of medicinal materials through process innovation and achieve the goal of enhancing the efficacy. This single protection idea limits the further improvement of the clinical application effect of Wenyujin.

[0008] Therefore, it is of great practical significance to develop a processing technology that can effectively protect the active ingredients of Curcuma wenyujin and improve its bioavailability through nanotechnology. This technology should not only solve the loss problem in the traditional processing process, but also improve the absorption and utilization efficiency of medicinal materials through nano-level processing, so as to achieve the dual goals of protection and efficiency enhancement, thereby meeting the needs of the modern Chinese medicine industry for efficient and high-quality products. Summary of the invention

[0009] The purpose of the present invention is to provide a nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma wenyujin. The nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma wenyujin can reduce the loss during the processing of Curcuma wenyujin and improve the efficacy of Curcuma wenyujin in the subsequent use process.

[0010] The above technical objectives of the present invention are achieved through the following technical solutions: A nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma wenyujin, comprising the following steps: (1) Basic protection treatment: Cleaning and screening the Curcuma aromatica raw materials; Mix Curcuma wenyujin with water at a ratio of 1:5-1:10 to form a slurry; The slurry is subjected to ultra-high pressure pulse treatment at a pressure of 500 MPa for 20 seconds; 40kHz ultrasonic wave was used to assist the pre-adsorption of mesoporous activated carbon for 2 minutes; Ultrasonic assisted cutting was performed in an argon environment at -5°C; (2) Biotransformation treatment: Microbial transformation was carried out by fermenting lactic acid bacteria LC-11 and Bacillus BY-5 at 32°C and pH 6.0 for 24 h; Chitosan-citric acid composite protective film was formed at pH 5.0; (3) Redox regulation treatment: Oxidative stress micro-stimulation was performed using 0.015-0.025% H2O2 solution at 4±1℃ for 90 seconds, and nano-cerium oxide was added as a redox regulator; Plasma activation treatment at 13.56 MHz frequency and 80 W power for 2 minutes; (4) Drug loading and coating treatment: Chitosan-hyaluronic acid composite nanoparticles were used to encapsulate ginkgolide and silymarin to construct an intelligent nano-drug delivery system; Supercritical CO was carried out at 25 MPa and 35 °C. 2 The fluid was allowed to dry for 4 hours; Cyclodextrin-phospholipid bilayer inclusion and packaging were performed.

[0011] Basic protection treatment also includes: activated carbon pre-adsorption using coconut shell activated carbon, with a specific surface area of ​​800-1200m 2 / g, the pore size distribution is 2-5nm accounting for 40-60%; the activated carbon pretreatment is activated at 300-500℃ for 2 hours, and the surface oxygen content is controlled at 15-25%; the pre-adsorption process is carried out under a vacuum degree of 0.05-0.08MPa and the temperature is controlled at 20±2℃.

[0012] Through the above technical scheme, the present invention constructs a multi-level protection and synergistic system through a reasonable combination of basic protection treatment, biological transformation treatment, redox regulation treatment, and drug loading and coating treatment, thereby achieving efficient protection of the active ingredients of Curcuma aromatica and improving their bioavailability. Through a precise concentration control system and multiple coating mechanisms, the stability and sustained-release effect of the active ingredients are ensured, while the synergistic effect of microbial transformation and redox regulation significantly enhances the efficacy.

[0013] The present invention is further configured as follows: the basic protection treatment also includes: activated carbon pre-adsorption using coconut shell activated carbon, the specific surface area of ​​800-1200m 2 / g, the pore size distribution is 2-5nm accounting for 40-60%; the activated carbon pretreatment is activated at 300-500℃ for 2 hours, and the surface oxygen content is controlled at 15-25%; the pre-adsorption process is carried out under a vacuum degree of 0.05-0.08MPa and the temperature is controlled at 20±2℃.

[0014] Through the above technical scheme, by optimizing the specific surface area, pore size distribution and surface oxygen content of activated carbon, combined with specific pretreatment and adsorption conditions, the selective adsorption capacity of activated carbon for non-target components in Curcuma aromatica was significantly improved, laying a good foundation for subsequent treatment. At the same time, temperature control under vacuum conditions ensured the stability of the active ingredients.

[0015] The present invention is further configured as follows: the preparation of the chitosan-citric acid composite protective film includes: the chitosan is selected from medical-grade chitosan with a deacetylation degree of 85-95% and a molecular weight of 50-200 kDa; the citric acid concentration is 0.5-2.0%, and the mass ratio of citric acid to chitosan is 1:1-3; the cross-linking reaction is carried out at 40-50° C. for 2-4 hours; the thickness of the protective film is controlled at 100-300 nm; and the cross-linking degree reaches 75-85%.

[0016] Through the above technical scheme, by selecting medical-grade chitosan with a specific deacetylation degree and molecular weight and optimizing the cross-linking reaction conditions with citric acid, a protective film with an ideal thickness and cross-linking degree is formed. The protective film not only provides a physical barrier effect, but also enhances the protective effect on the active ingredients through the coordination effect of citric acid.

[0017] The present invention is further configured as follows: the oxidative stress micro-stimulation treatment includes: the H2O2 solution is diluted with medical-grade hydrogen peroxide; the nano-cerium oxide particle size is 20-50nm, the concentration is 0.01-0.05%; the surface Ce of the cerium oxide 3+ / Ce 4+ The ratio is 0.3-0.5; the solution pH is controlled at 6.8-7.2 during the treatment process; the residual H2O2 concentration after treatment is ≤0.001%.

[0018] Through the above technical solution, the surface Ce 3+ / Ce 4+ ratio, establishing a dynamically balanced redox regulation system, achieving a mild and controllable oxidative stress micro-stimulation effect, while ensuring that the residual hydrogen peroxide concentration after treatment meets safety requirements.

[0019] The present invention is further configured as follows: the microbial transformation process includes: the number of viable bacteria of lactic acid bacteria LC-11 is ≥ 1×10 9 CFU / g; the number of viable bacteria of Bacillus BY-5 ≥1×10 8 CFU / g; the inoculation ratio of the two strains is 1:1-3; the fermentation medium contains: glucose 2-4%, yeast extract 0.5-1.5%, peptone 1-2%; the dissolved oxygen content during the fermentation process is maintained at 30-40%; the pH of the fermentation liquid is automatically controlled at 6.0±0.2.

[0020] Through the above technical scheme, by controlling the live bacterial count and inoculation ratio of the two strains and optimizing the fermentation medium composition and fermentation conditions, an efficient microbial transformation process is achieved, the biotransformation efficiency and bioavailability of the active ingredients are improved, and the precise control of the fermentation process ensures the stability and uniformity of the transformation products.

[0021] The present invention is further configured as follows: the intelligent nano drug delivery system comprises: chitosan-hyaluronic acid composite nanoparticles with a particle size of 100-300nm; zeta potential of +20 to +40mV; encapsulation efficiency of 85-95%; drug loading of 15-25%; hyaluronic acid molecular weight of 500-1500kDa; and nanoparticle polydispersity coefficient ≤0.2.

[0022] Through the above technical scheme, efficient drug encapsulation and drug loading capacity are achieved by regulating the physicochemical properties of chitosan-hyaluronic acid composite nanoparticles. The optimization of the particle size distribution and surface potential of the nanoparticles ensures good dispersibility and stability, providing effective protection and controlled release for the active ingredients.

[0023] The present invention is further configured as follows: plasma activation treatment includes: using argon as a working gas with a purity of ≥99.999%; the gas pressure is controlled at 50-100 Pa; the treatment temperature does not exceed 40°C; the distance between the sample and the plasma source is 10-15 cm; and the relative humidity of the treatment chamber is controlled at 30-40%.

[0024] Through the above technical scheme, by precisely controlling the working parameters of the plasma activation treatment, including gas purity, pressure, temperature and treatment distance, a gentle and effective surface modification effect is achieved, which improves the binding ability and stability of the subsequent drug delivery system, while avoiding the damage of high temperature to the active ingredients.

[0025] The present invention is further configured as follows: supercritical CO 2 Fluid drying process includes: CO 2 Purity ≥99.99%; pressure rise rate is 2-3MPa / min; temperature fluctuation range during drying is ±0.5℃; ethanol is added as a co-solvent with a concentration of 3-5%; moisture content after drying is controlled below 3%.

[0026] Through the above technical solution, by controlling the supercritical CO 2 The process parameters for fluid drying, including pressure ramp rate, temperature fluctuation range and co-solvent concentration, achieve gentle and efficient drying effects, ensure low moisture content and ideal physical state of the product, and are conducive to the long-term stability of the finished product.

[0027] The present invention is further configured as follows: cyclodextrin-phospholipid bilayer inclusion includes: using β-cyclodextrin with a purity of ≥99%; the phospholipid is soybean lecithin, and the phosphatidylcholine content is ≥80%; the mass ratio of cyclodextrin to phospholipid is 1:0.5-2; the inclusion process is carried out at 45-55°C; the inclusion compound particle size distribution is 200-500nm; and the inclusion rate reaches 90-95%.

[0028] Through the above technical scheme, high-purity β-cyclodextrin and phospholipids of specific composition are used, and the inclusion conditions are optimized to form a double-layer protective structure with ideal particle size distribution and high inclusion rate. This structure not only provides additional protection, but also improves the biocompatibility and absorbability of the product.

[0029] The present invention is further provided as follows: an application of the Curcuma wenyujin preparation prepared by the above processing technology in the preparation of anti-inflammatory, antioxidant and immunomodulatory drugs.

[0030] Through the above technical scheme, the Wenyujin preparation prepared by the present invention shows significant effects in the application of anti-inflammatory, antioxidant and immunomodulatory drugs, achieves better therapeutic effects through multiple action mechanisms, and has important clinical application value and promotion prospects.

[0031] In summary, the present invention has the following beneficial effects: The core innovation of this invention is to build a multi-level collaborative system of "protection-efficiency-stabilization", the mechanism of which is as follows: The active ingredient system of Wenyujin is complex, mainly including three categories: Volatile oils: account for 2-5% of the total mass, and the main components include monoterpenes and sesquiterpenes such as α-pinene (15-20%), β-pinene (12-15%), camphene (8-10%), and curcuminol (5-8%). These components generally have the characteristics of small molecular weight (154-222) and low boiling point (150-180℃). The molecules contain unsaturated bonds and are prone to oxidation and isomerization. At the same time, they are highly fat-soluble and have poor stability in the aqueous phase.

[0032] Curcuminoids: 1-3% of the total mass, including curcumin (35-40%), demethoxycurcumin (15-20%) and bisdemethoxycurcumin (10-15%). The molecular structure of this type of compound contains a characteristic β-diketone structure, which is easily hydrolyzed in an environment of pH>7; the methoxy and hydroxyl groups on the benzene ring give it strong antioxidant activity, but also lead to strong photothermal sensitivity. The conjugated double bond system in the molecule is prone to cis-trans isomerization under light conditions.

[0033] Sesquiterpenoids: mainly include turmeric ketone (0.5-0.8%), turmeric alcohol (0.3-0.5%), etc. The molecular weight of this type of compound is between 220-280, contains multiple unsaturated bonds and active hydroxyl groups, and is easily oxidized. Its spatial conformation is sensitive to temperature, and heating can easily lead to conformational transformation and affect activity.

[0034] Initial release stage: Ultrahigh pressure pulses cause the cell membrane phospholipid molecules to rearrange, the head group spacing is reduced from 0.9nm to 0.7nm, and the tail carbon chain changes from disordered arrangement to parallel arrangement. This conformational change leads to a decrease in membrane fluidity, and at the same time, a transient channel with a diameter of 15-20nm is formed under the action of the pressure gradient. Ultrasonic cavitation (40kHz, power density 0.2W / cm 2 ) to promote the directional movement of active ingredients in the cytoplasm. This process maintains the integrity of volatile oils while achieving the gentle release of curcuminoids, allowing curcuminoids to be freed from the internal structure of the cells of Curcuma longifolia, facilitating the subsequent efficacy of the drug.

[0035] Molecular recognition and separation: The pore size distribution of mesoporous activated carbon matches the size of curcumin molecules, and selectively adsorbs aromatic impurities through π-π stacking. The surface modification of mesoporous activated carbon introduces surface carboxyl (-COOH), hydroxyl (-OH) and other functional groups to form a hydrogen bond network with curcumin molecules, achieving precise separation of target molecules.

[0036] Multiple protection system: Chitosan and citric acid are cross-linked to form a network structure with a mesh size of 3-5nm. The amino group forms a Schiff base bond with the carbonyl group of the curcumin molecule. At the same time, the network structure restricts the freedom of molecular movement and effectively prevents the escape of volatile oil. β-cyclodextrin (cavity diameter 0.7nm, depth 0.8nm) forms an inclusion complex with the aromatic ring of curcumin through hydrophobic interaction. The phospholipid bilayer is further wrapped, and the oxygen permeability coefficient is reduced to 1 / 5 of the original.

[0037] Active enhancement system: Nano cerium oxide (particle size 5-10nm) through Ce 3+ / Ce 4+ Cycle (redox potential +1.61V) to remove superoxide anion free radicals (produced when the active ingredients of Curcuma zedoaria come into contact with oxygen, which will attack the active ingredients in Curcuma zedoaria, such as destroying the unsaturated bonds in the curcumin molecule, oxidizing the compounds in the volatile oil, etc.), while nano-cerium oxide maintains the hydrogen peroxide concentration in the range of 0.1-1μM, activating the Nrf2 signaling pathway. In the dual-strain fermentation system, β-glucosidase selectively hydrolyzes glycosidic bonds, and the oxidoreductase system (ECR1.3.1) catalyzes the hydrogenation of some unsaturated bonds in the curcumin molecule to improve stability.

[0038] Nano-cerium oxide regulates redox balance, the drug delivery system provides a physical barrier, and the cyclodextrin-phospholipid bilayer inclusion provides further protection. The above process makes the nano-particles after the treatment of Wenyujin show a significant advantage of sustained release effect. Not only can the multiple protection system prevent the rapid consumption of hydrogen peroxide due to its unstable nature, but it can also maintain a stable low concentration range and prolong the action time. Combining oxidative stress micro-stimulation, redox regulation and multiple coatings to form a synergistic overall system, thereby achieving a regulatory effect.

[0039] In the active enhancement system. Hydrogen peroxide will cause oxidative degradation of the active ingredients of Curcumin. Specifically, the β-diketone structure in the curcumin molecule is ring-opened under the action of hydrogen peroxide, and the phenolic hydroxyl group is oxidized to form a quinone structure and loses its antioxidant activity; the unsaturated bonds in the volatile oil are attacked by hydrogen peroxide to form epoxides, which are further ring-opened to form aldehydes and ketones; the active hydroxyl groups of sesquiterpenoid compounds are oxidized to carbonyl groups, and the double bonds in the molecules are oxidized and broken. The above process not only reduces the content of active ingredients, but also produces free radicals that further accelerate the degradation process.

[0040] The present invention achieves reverse synergy by constructing a precise redox regulation network to maintain the concentration of hydrogen peroxide at a beneficial level (0.1-1 μM). 4+ / Ce 3+ The reversible conversion of hydrogen peroxide can precisely adjust the concentration of hydrogen peroxide, and its surface oxygen vacancies (concentration 3.5×1019 / cm³) can reversibly adsorb H2O2 to maintain homeostasis. In the human body, low concentrations of hydrogen peroxide act as signal molecules to promote the dissociation of Keap1 and Nrf2 in human cells. After free Nrf2 is translocated into the nucleus, it binds to the ARE element and initiates the transcription of antioxidant genes such as HO-1 and NQO1. At the same time, the enzymatic network composed of catalase (200U / mg), glutathione peroxidase (150U / mg) and superoxide dismutase (300U / mg) synergistically regulates the cellular redox balance. Activate the body's own antioxidant defense system. By converting destructive hydrogen peroxide into beneficial signal molecules, low concentrations of hydrogen peroxide (0.1-1μM) act as a second messenger, oxidizing key cysteine ​​residues (Cys151, Cys273 and Cys288) on the Keap1 protein, causing Keap1 conformational changes, releasing the originally bound Nrf2 and translocating it into the nucleus. After free Nrf2 forms a heterodimer with the small Maf protein, it specifically binds to the ARE sequence and initiates the transcription of multiple antioxidant genes. The group of antioxidant enzymes produced by this transcriptional activation includes not only superoxide dismutase (SOD) and catalase (CAT) that directly scavenge free radicals, but also γ-glutamylcysteine ​​ligase (γ-GCS) and glutathione reductase (GR) that participate in the synthesis and circulation of glutathione (GSH). At the same time, the upregulation of NAD(P)H quinone oxidoreductase 1 (NQO1) enhances the metabolic activation of cells to the active ingredients of Curcuma wenyujin, and the expression of heme oxygenase-1 (HO-1) provides additional anti-inflammatory and antioxidant protection. This multi-level defense network not only protects curcumin, volatile oils and sesquiterpenoids in Curcuma wenyujin from oxidative damage, but more importantly, it significantly enhances the biological effects of these active ingredients through the cascade amplification effect of cell signaling pathways.

[0041] Nano delivery system: Nano carriers (particle size 150±20nm, PDI<0.2) are formed by electrostatic self-assembly of chitosan (+25mV) and hyaluronic acid (-30mV). Surface modification with PEG2000 improves stability, and the Zeta potential is controlled at +15mV to ensure good dispersibility. The pH-sensitive bond (hydrazide bond) is hydrolyzed under weakly acidic conditions to achieve directional release of curcuminoids. DETAILED DESCRIPTION

[0042] A nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma wenyujin, comprising the following steps: (1) Basic protection treatment: Cleaning and screening the Curcuma aromatica raw materials; Mix Curcuma wenyujin with water at a ratio of 1:5-1:10 to form a slurry; The slurry is subjected to ultra-high pressure pulse treatment at a pressure of 500 MPa for 20 seconds; 40kHz ultrasonic wave was used to assist the pre-adsorption of mesoporous activated carbon for 2 minutes; Ultrasonic assisted cutting was performed in an argon environment at -5°C; (2) Biotransformation treatment: Microbial transformation was carried out by fermenting lactic acid bacteria LC-11 and Bacillus BY-5 at 32°C and pH 6.0 for 24 h; Chitosan-citric acid composite protective film was formed at pH 5.0; (3) Redox regulation treatment: Oxidative stress micro-stimulation was performed using 0.015-0.025% H2O2 solution at 4±1℃ for 90 seconds, and nano-cerium oxide was added as a redox regulator; Plasma activation treatment at 13.56 MHz frequency and 80 W power for 2 minutes; (4) Drug loading and coating treatment: Chitosan-hyaluronic acid composite nanoparticles were used to encapsulate ginkgolide and silymarin to construct an intelligent nano-drug delivery system; Supercritical CO was carried out at 25 MPa and 35 °C. 2 The fluid was allowed to dry for 4 hours; Cyclodextrin-phospholipid bilayer inclusion and packaging were performed.

[0043] Basic protection treatment also includes: activated carbon pre-adsorption using coconut shell activated carbon, with a specific surface area of ​​800-1200m 2 / g, the pore size distribution is 2-5nm accounting for 40-60%; the activated carbon pretreatment is activated at 300-500℃ for 2 hours, and the surface oxygen content is controlled at 15-25%; the pre-adsorption process is carried out under a vacuum degree of 0.05-0.08MPa and the temperature is controlled at 20±2℃.

[0044] The preparation of chitosan-citric acid composite protective film includes: chitosan is selected from medical grade chitosan with a deacetylation degree of 85-95% and a molecular weight of 50-200kDa; the concentration of citric acid is 0.5-2.0%, and the mass ratio of citric acid to chitosan is 1:1-3; the cross-linking reaction is carried out at 40-50°C for 2-4 hours; the thickness of the protective film is controlled at 100-300nm; and the degree of cross-linking reaches 75-85%.

[0045] Oxidative stress micro-stimulation treatment includes: H2O2 solution is diluted with medical grade hydrogen peroxide; the particle size of nano-cerium oxide is 20-50nm, the concentration is 0.01-0.05%; Ce on the surface of cerium oxide 3+ / Ce 4+ The ratio is 0.3-0.5; the solution pH is controlled at 6.8-7.2 during the treatment process; the residual H2O2 concentration after treatment is ≤0.001%.

[0046] The microbial transformation process includes: the number of viable lactic acid bacteria LC-11 ≥ 1×10 9 CFU / g; the number of viable bacteria of Bacillus BY-5 ≥1×10 8 CFU / g; the inoculation ratio of the two strains is 1:1-3; the fermentation medium contains: glucose 2-4%, yeast extract 0.5-1.5%, peptone 1-2%; the dissolved oxygen content during the fermentation process is maintained at 30-40%; the pH of the fermentation liquid is automatically controlled at 6.0±0.2.

[0047] The intelligent nano drug delivery system includes: chitosan-hyaluronic acid composite nanoparticles with a particle size of 100-300nm; zeta potential of +20 to +40mV; encapsulation efficiency of 85-95%; drug loading of 15-25%; hyaluronic acid molecular weight of 500-1500kDa; and nanoparticle polydispersity coefficient ≤0.2.

[0048] Plasma activation treatment includes: using argon as working gas with a purity of ≥99.999%; controlling the gas pressure at 50-100 Pa; the treatment temperature not exceeding 40°C; the distance between the sample and the plasma source is 10-15 cm; and controlling the relative humidity of the treatment chamber at 30-40%.

[0049] Supercritical CO 2 Fluid drying process includes: CO 2 Purity ≥99.99%; pressure rise rate is 2-3MPa / min; temperature fluctuation range during drying is ±0.5℃; ethanol is added as a co-solvent with a concentration of 3-5%; moisture content after drying is controlled below 3%.

[0050] The cyclodextrin-phospholipid bilayer inclusion process includes: using β-cyclodextrin with a purity of ≥99%; the phospholipid is soybean lecithin with a phosphatidylcholine content of ≥80%; the mass ratio of cyclodextrin to phospholipid is 1:0.5-2; the inclusion process is carried out at 45-55°C; the inclusion compound particle size distribution is 200-500nm; and the inclusion rate reaches 90-95%.

[0051] In view of the above process, the present invention designs the experiment as follows: 1. Experimental groups are shown in Table 1 below:

[0052] 2. Experimental conditions 2.1 Main equipment, as shown in Table 2 below:

[0053] 2.2 Environmental conditions, as shown in Table 3 below:

[0054] 3. Experimental results (1) Physical property indicators, as shown in Table 4 below:

[0055] (2) Chemical composition analysis, as shown in Table 5 below:

[0056] (3) Biological activity evaluation, as shown in Table 6 below:

[0057] (4) Stability evaluation (6 months), as shown in Table 7 below:

[0058] 4. Result analysis: (1) Analysis of physical properties: The EXP5 group performed best, with an average particle size of 175±12nm and the lowest PDI value of 0.148, indicating that the particle size distribution was the most uniform; in terms of Zeta potential, the EXP5 group reached +33.2mV, indicating that the system had good stability; the encapsulation efficiency of the experimental groups (EXP1-5) was significantly better than that of the control group, among which EXP5 reached 94.1%, much higher than the 45.6% of the conventional method (CTL2); SEM morphological observation showed that the uniformity of the experimental groups was significantly better than that of the control group, especially the EXP5 group reached a higher level.

[0059] (2) Chemical composition analysis: Active ingredient retention rate: The experimental group was significantly higher than the control group, and the EXP5 group had the highest indicators (volatile oil 4.45%, curcumin 2.78%, sesquiterpenes 1.22%); Antioxidant activity: The DPPH clearance rate of the EXP5 group reached 88.2%, nearly double that of the control group CTL1 (45.3%); Total flavonoid content: The EXP5 group reached 45.6 mg / g, about twice that of CTL1 (22.4 mg / g).

[0060] (3) Biological activity evaluation: Cell safety: The cell survival rate of all experimental groups was >90%, indicating good biocompatibility; anti-inflammatory effect: The EXP5 group showed the strongest IL-6 and TNF-α inhibition effects (72.3% and 68.9%, respectively); Nrf2 activation: The EXP5 group reached 2.65, showing the strongest antioxidant pathway activation ability; bioavailability: The EXP5 group reached 196% of the original level, a significant improvement.

[0061] (4) Stability evaluation: The 6-month stability data showed that the EXP5 group had the highest retention rate of various indicators; active ingredient retention: the volatile oil retention rate of the EXP5 group was 94.2%, and the curcumin retention rate was 92.6%; moisture control: the EXP5 group had the lowest moisture content (2.8%), which is conducive to long-term storage; morphological stability: the EXP5 group remained highly stable, while the control group had stability problems to varying degrees.

[0062] 5. Conclusion The present invention has established a complete active ingredient protection mechanism through a multi-level protection system such as basic protection treatment, biotransformation treatment, redox regulation and drug-carrying coating, which not only solves the problem of easy degradation of active ingredients in traditional processing, but also significantly improves bioavailability through nanotechnology. The chitosan-citric acid composite protective film and cyclodextrin-phospholipid bilayer inclusion used in the process provide physical and chemical dual protection, and the parameters such as precisely controlled pressure, temperature, pH, etc. improve the stability of the processing process. At the same time, biotransformation is carried out by the coordinated fermentation of lactic acid bacteria and bacillus, and the mild regulation of the redox regulation system is coordinated to achieve the synergism of active ingredients. The intelligent nano drug-carrying system finally formed has a high encapsulation rate and an ideal drug loading, can achieve the directional release of drugs, and improves the medicinal value and clinical application effect of Wenyujin as a whole.

[0063] This specific embodiment is merely an explanation of the present invention and is not a limitation of the present invention. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed. However, as long as they are within the scope of the claims of the present invention, they are protected by the patent law.

Claims

1. A nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma wenyujin, characterized in that: The following steps are involved: (1) Basic protection treatment: Cleaning and screening the Curcuma aromatica raw materials; Mix Curcuma wenyujin with water at a ratio of 1:5-1:10 to form a slurry; The slurry is subjected to ultra-high pressure pulse treatment at a pressure of 500 MPa for 20 seconds; 40kHz ultrasonic wave was used to assist the pre-adsorption of mesoporous activated carbon for 2 minutes; Ultrasonic assisted cutting was performed in an argon environment at -5°C; (2) Biotransformation treatment: Microbial transformation was carried out by fermenting lactic acid bacteria LC-11 and Bacillus BY-5 at 32°C and pH 6.0 for 24 h; Chitosan-citric acid composite protective film was formed at pH 5.0; (3) Redox regulation treatment: Oxidative stress micro-stimulation was performed using 0.015-0.025% H2O2 solution at 4±1℃ for 90 seconds, and nano-cerium oxide was added as a redox regulator; Plasma activation treatment at 13.56 MHz frequency and 80 W power for 2 minutes; (4) Drug loading and coating treatment: Chitosan-hyaluronic acid composite nanoparticles were used to encapsulate ginkgolide and silymarin to construct an intelligent nano-drug delivery system; Supercritical CO was carried out at 25 MPa and 35 °C. 2 The fluid was allowed to dry for 4 hours; Cyclodextrin-phospholipid bilayer inclusion and packaging were performed.

2. The nanoscale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma aromatica according to claim 1 is characterized in that: The basic protection process also includes: The activated carbon pre-adsorption adopts coconut shell activated carbon with a specific surface area of ​​800-1200m 2 / g, pore size distribution is 2-5nm accounting for 40-60%; The activated carbon pretreatment is activated at 300-500℃ for 2 hours, and the surface oxygen content is controlled at 15-25%; The pre-adsorption process is carried out under a vacuum degree of 0.05-0.08MPa and the temperature is controlled at 20±2°C.

3. The nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma aromatica according to claim 1 is characterized in that: The preparation of the chitosan-citric acid composite protective film includes: selecting medical-grade chitosan with a deacetylation degree of 85-95% and a molecular weight of 50-200 kDa; the concentration of citric acid is 0.5-2.0%, and the mass ratio of citric acid to chitosan is 1:1-3; the cross-linking reaction is carried out at 40-50° C. for 2-4 hours; the thickness of the protective film is controlled at 100-300 nm; and the cross-linking degree reaches 75-85%.

4. The nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma aromatica according to claim 1 is characterized in that: The oxidative stress micro-stimulation treatment includes: the H2O2 solution is made by diluting medical-grade hydrogen peroxide; the nano-cerium oxide particle size is 20-50nm and the concentration is 0.01-0.05%; the surface Ce of the cerium oxide 3+ / Ce 4+ The ratio is 0.3-0.5; the solution pH is controlled at 6.8-7.2 during the treatment process; the residual H2O2 concentration after treatment is ≤0.001%.

5. The nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma aromatica according to claim 1 is characterized in that: The microbial transformation process includes: the number of viable bacteria of lactic acid bacteria LC-11 is ≥ 1×10 9 CFU / g; the number of viable bacteria of Bacillus BY-5 ≥1×10 8 CFU / g; the inoculation ratio of the two strains is 1:1-3; the fermentation medium contains: glucose 2-4%, yeast extract 0.5-1.5%, peptone 1-2%; the dissolved oxygen content during the fermentation process is maintained at 30-40%; the pH of the fermentation liquid is automatically controlled at 6.0±0.

2.

6. The nanoscale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma aromatica according to claim 1 is characterized in that: The intelligent nano drug delivery system comprises: chitosan-hyaluronic acid composite nanoparticles with a particle size of 100-300nm; zeta potential of +20 to +40mV; encapsulation efficiency of 85-95%; drug loading of 15-25%; hyaluronic acid molecular weight of 500-1500kDa; and nanoparticle polydispersity coefficient ≤0.

2.

7. The nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma aromatica according to claim 1 is characterized in that: The plasma activation treatment includes: using argon as working gas with a purity of ≥99.999%; controlling the gas pressure at 50-100 Pa; the treatment temperature not exceeding 40° C.; the distance between the sample and the plasma source is 10-15 cm; and controlling the relative humidity of the treatment chamber at 30-40%.

8. The nano-scale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma aromatica according to claim 1 is characterized in that: The supercritical CO 2 Fluid drying process includes: CO 2 Purity ≥99.99%; pressure rise rate is 2-3MPa / min; temperature fluctuation range during drying is ±0.5℃; ethanol is added as a co-solvent with a concentration of 3-5%; moisture content after drying is controlled below 3%.

9. The nanoscale processing technology for protecting and enhancing the high-efficiency active ingredients of Curcuma aromatica according to claim 1, characterized in that: The cyclodextrin-phospholipid bilayer inclusion process includes: using β-cyclodextrin with a purity of ≥99%; the phospholipid is soybean lecithin with a phosphatidylcholine content of ≥80%; the mass ratio of cyclodextrin to phospholipid is 1:0.5-2; the inclusion process is carried out at 45-55°C; the inclusion compound particle size distribution is 200-500nm; and the inclusion rate reaches 90-95%.

10. A Curcuma wenyujin preparation prepared by the processing technology according to any one of claims 1 to 9, characterized in that: Application in the preparation of anti-inflammatory, antioxidant and immunomodulatory drugs.

Images