Nutrient composition for delaying impaired vision based on multi-mode targeted delivery and preparation method thereof

Abstract

The invention relates to the technical field of functional nutritional compositions, and particularly discloses a nutritional composition for delaying impaired vision based on multi-mode targeted delivery and a preparation method, the nutritional composition comprises mitochondrial targeted nanoparticles, light protection compound microcapsules, neuroinflammation regulation nanocrystals and epigenetic activator powder, and microbiome synergistic sustained-release particles. The quick-release and slow-release double-layer tablet is obtained by preparing in different modules and then pressing in batches or coating and forming. Different effective components are respectively prepared into the quick release layer and the slow release layer, so that 30% of the quick release layer is released in gastric juice within 5 minutes, and the acute deficiency symptom is quickly relieved; the sustained-release layer maintains the steady-state blood concentration for 12 hours through a swelling diffusion mechanism, the blood peak valley fluctuation rate is reduced to be within + / -15%, the technical effect of precise space-time release is achieved, and due to targeted delivery and high-concentration retention of various effective components, the remarkable effect exceeding expectation is obtained.

Description

Technical Field

[0001] The present invention relates to the technical field of nutritional compositions, and in particular to the technical field of breaking through the bottleneck of bioavailability by combining targeted delivery, colon circumcision and nanocarrier technology, and specifically to a nutritional composition for delaying vision loss based on multimodal targeted delivery and a preparation method thereof. Background Art

[0002] In the current environment where intelligent devices are prevalent, people from all walks of life and all ages will inevitably come into contact with electronic products. Although in the era of intelligence, electronic products have brought great convenience to people's lives, work, and learning, and improved efficiency by an order of magnitude, it is inevitable that people use their eyes at close range for a long time, which makes people's vision face severe tests. The age at which vision declines gradually decreases, coupled with other factors such as ultraviolet exposure, smoking, and malnutrition, which makes vision decline more serious and even gradually becomes a common phenomenon. Therefore, the problem of protecting eyesight and delaying vision decline needs to be solved urgently, and the situation is very serious.

[0003] Although there are many oral nutritional products, dietary products, and even health-care drugs in the prior art that are helpful in protecting eyesight and delaying vision loss, the actual oral effects are minimal and not significant. The main reasons are as follows: First, the absorption of fat-soluble ingredients depends on fat. For example, vitamin A, DHA, etc. are fat-soluble substances and need to be ingested with dietary fat to be absorbed by the intestines. This significantly reduces the absorption rate for people with low-fat diets or insufficient bile secretion (such as gallbladder disease). Second, the intestinal barrier and transport protein restrictions. Some active ingredients (such as anthocyanins and polyphenols) need to be absorbed through intestinal specific transport proteins SCLT1 and GLUT2. If the corresponding active ingredients do not reach the designated intestine or exceed the carrying capacity of the transport protein when they reach the designated intestine, they will not be absorbed. Third, after the oral ingredients enter the liver through the portal vein, some are metabolized and inactivated. For example, DHA may be oxidized and decomposed in the liver, and ultimately cannot achieve the effect of protecting vision. In summary, the existing nutritional compositions are not effective in protecting vision because some of the active ingredients will be oxidized and decomposed in advance, and cannot reach the designated parts, resulting in no effective absorption and no actual effect. In addition, some active ingredients require specific conditions to be effectively absorbed, which ultimately leads to the fact that the actual effect on vision protection is not significant. Summary of the invention

[0004] In order to solve the problem that the existing nutritional compositions or similar health products have poor actual effects on protecting eyesight and delaying vision loss, the present application provides a nutritional composition and a preparation method for delaying vision loss based on multimodal targeted delivery. Through the triple combination technology of layered controlled release, carrier synergy and intelligent response, the delivery of active ingredients of the present invention breaks through the traditional bottleneck.

[0005] In order to achieve the above purpose, the technical solution adopted in this application is: The present invention provides a nutritional composition for delaying vision loss based on multimodal targeted delivery, comprising mitochondrial targeted nanoparticles, photoprotective complex microcapsules, neuroinflammation regulating nanocrystals, epigenetic activator powder, and microbiome synergistic sustained-release particles; the mitochondrial targeted nanoparticles are composed of lutein, zeaxanthin, SS-31 peptide, and coenzyme Q10 in a weight ratio of 10:2:50:0.5; the photoprotective complex microcapsules are composed of anthocyanidins, crocetin, and astaxanthin in a weight ratio of 100:5:4; the neuroinflammation regulating nanocrystals are composed of boswellic acid, curcumin, and berberine in a weight ratio of 150:50:25; the epigenetic activator powder is composed of sulforaphane and EGCG in a weight ratio of 15:100; the microbiome synergistic sustained-release particles are composed of GOS, arabinoxylan, and sodium butyrate in a weight ratio of 50:300:200.

[0006] The present invention also provides a method for preparing a nutritional composition, which is used to prepare the nutritional composition for delaying vision loss based on multimodal targeted delivery as described above, comprising the following steps: preparing mitochondrial targeting nanoparticles, photoprotection complex microcapsules, neuroinflammation regulating nanocrystals, epigenetic activator powder, and microbiome synergistic sustained-release particles separately and separately in modules; The method for preparing mitochondrial targeting nanoparticles comprises: Step STP110, lipid film formation: Phosphatidylcholine, cholesterol and SS-31 peptide were dissolved in chloroform at a weight ratio of 7:2:1, and rotary evaporated at 40°C and 0.1 MPa to form a uniform film; Step STP120, active ingredient loading: lutein and zeaxanthin dissolved in anhydrous ethanol are mixed with coenzyme Q10 dissolved in olive oil, added into a phosphate buffer with pH = 7.4, and hydrated at 50°C for 1 hour; Step STP130, high pressure homogenization: using a high pressure homogenizer at 1000 bar, cycle 3 times to obtain a light yellow translucent suspension of nanoparticles with a particle size of 80-120 nm; Step STP140, spray drying: the nano suspension is mixed with a protective agent and then spray dried to form a dry powder with a particle size of ≤10 μm and an encapsulation rate of >95%, wherein the protective agent is a mixture of mannitol and trehalose, and the spray drying conditions are: inlet temperature 80-100°C, outlet air temperature 40-50°C; The method for preparing the light protection composite microcapsules comprises: Step STP210, core material emulsification: anthocyanidin, crocetin, and astaxanthin are mixed in a weight ratio of 20:1:0.8, 10% gum arabic aqueous solution is added, and high-speed shear emulsification is performed at 10,000 rpm for 10 minutes to obtain an emulsified solution; Step STP220, spray drying: drying the emulsified solution obtained in step STP210 under the conditions of an inlet air temperature of 160°C, an outlet air temperature of 80°C, and an atomization pressure of 0.3 MPa to obtain dark purple fluid powder microcapsules; The method for preparing the neuroinflammation regulating nanocrystals comprises: Step STP310, nanocrystal preparation: curcumin and Pluronic F127 were dissolved in acetone at a ratio of 1:3, dropped into ultrapure water and magnetically stirred for 24 hours, and the nanoparticle crystals were collected by centrifugation; Step STP320, dry mixing: uniformly mixing the boswellic acid, berberine and curcumin nanocrystals by a three-dimensional mixer at 30 rpm for 30 minutes to obtain an orange-red powder; The preparation method of the epigenetic activator powder comprises: freeze drying: sulforaphane and EGCG are mixed in a mass ratio of 1:6.7, dissolved in deionized water, pre-frozen at -80°C, and then placed in a 0.1 mbar environment for vacuum drying for 24 hours to obtain a light green loose powder; The preparation method of the microbiome synergistic sustained-release particles comprises: placing sodium butyrate core particles in a fluidized bed, and spraying Eudragit® L100 with a weight of 5% of the total weight of the sodium butyrate core particles and Eudragit® FS30D with a weight of 10% of the total weight of the sodium butyrate core particles in sequence; then mixing GOS, arabinoxylan and the coated sodium butyrate core particles by a V-type mixer at 20 rpm for 15 minutes to obtain white to beige particles; the Eudragit® FS30D refers to sodium butyrate.

[0007] Then, the photoprotective complex microcapsules, neuroinflammation regulating nanocrystals and microbiome synergistic sustained-release granules were wet granulated and then tableted to obtain a sustained-release layer; Finally, the mitochondrial targeting nanoparticles and epigenetic activator powder are directly compressed to obtain a quick-release layer and then compressed together with the sustained-release layer or wrapped outside the sustained-release layer.

[0008] Beneficial effects: 1. By preparing different active ingredients into immediate-release layer and sustained-release layer respectively, the immediate-release layer releases 30% of the dose in gastric juice within 5 minutes, quickly relieving acute deficiency symptoms; the sustained-release layer maintains a steady-state blood drug concentration for 12 hours through a swelling and diffusion mechanism, and the peak-to-valley fluctuation rate of the blood drug is reduced to within ±15%, achieving the technical effect of precise temporal and spatial release.

[0009] 2. The colon targeting layer of the present invention protects the survival rate of probiotics to >85%, and accurately releases them in the ileocecal region; in addition, the nanoliposome encapsulates lutein, which improves the efficiency of passing through the blood-ocular barrier and increases the amount of retinal drug deposition.

[0010] 3. The flavin-piperine PLGA cocrystal system of the present invention prolongs the liver metabolic half-life to 14 hours, and the bioavailability can be theoretically increased by 18 times. The iron ions are co-delivered with ascorbic acid microcapsules, and the absorption rate can be increased from the current 12% to a maximum of 68%, which is 5 times that of existing similar products. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without paying any creative labor.

[0012] Figure 1 It is a process flowchart of a biological oral targeted nutritional composition from ingestion to the final production of medicinal effects. DETAILED DESCRIPTION

[0013] In order to make the purpose, technical solution and advantages of the embodiments of the present application clearer, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. The components of the embodiments of the present application described and shown in the drawings here can be arranged and designed in various different configurations.

[0014] Therefore, the following detailed description of the embodiments of the present application provided in the accompanying drawings is not intended to limit the scope of the present application for which protection is sought, but merely represents selected embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present application.

[0015] Embodiment 1: The present embodiment provides a nutritional composition for delaying vision loss based on multimodal targeted delivery, including mitochondrial targeted nanoparticles, photoprotective complex microcapsules, neuroinflammation regulating nanocrystals, epigenetic activator powder, and microbiome synergistic sustained-release particles; the mitochondrial targeted nanoparticles are composed of lutein, zeaxanthin, SS-31 peptide, and coenzyme Q10 in a weight ratio of 10:2:50:0.5; the photoprotective complex microcapsules are composed of anthocyanidins, crocetin, and astaxanthin in a weight ratio of 100:5:4; the neuroinflammation regulating nanocrystals are composed of boswellic acid, curcumin, and berberine in a weight ratio of 150:50:25; the epigenetic activator powder is composed of sulforaphane and EGCG in a weight ratio of 15:100; the microbiome synergistic sustained-release particles are composed of GOS, arabinoxylan, and sodium butyrate in a weight ratio of 50:300:200. The mitochondrial targeted nanoparticles are used to target the repair of retinal mitochondrial damage, the photoprotective complex microcapsules are used to absorb blue light and neutralize phototoxic ROS, the neuroinflammation regulating nanocrystals are used to inhibit excessive activation of retinal microglia, the epigenetic activator powder is used to activate antioxidant genes through DNA demethylation, the microbiome synergistic sustained-release particles are used to regulate the intestinal flora-retina axis, and the sustained-release butyrate strengthens the blood-retina barrier.

[0016] Embodiment 2: This embodiment provides a method for preparing a nutritional composition, which is used to prepare a nutritional composition for delaying vision loss based on multimodal targeted delivery as described in Example 1. The nutritional composition of this embodiment is prepared by preparing components with different functions separately, and finally preparing different components separately according to different sites and stages of biological absorption, specifically comprising the following steps: preparing mitochondrial targeting nanoparticles, photoprotection complex microcapsules, neuroinflammation regulating nanocrystals, epigenetic activator powder, and microbiome synergistic sustained-release particles separately and separately; The method for preparing mitochondrial targeting nanoparticles comprises: Step STP110, lipid film formation: Phosphatidylcholine, cholesterol and SS-31 peptide were dissolved in chloroform at a weight ratio of 7:2:1, and rotary evaporated at 40°C and 0.1 MPa to form a uniform film; Step STP120, active ingredient loading: lutein and zeaxanthin dissolved in anhydrous ethanol are mixed with coenzyme Q10 dissolved in olive oil, added into a phosphate buffer with pH = 7.4, and hydrated at 50°C for 1 hour; Step STP130, high pressure homogenization: using a high pressure homogenizer at 1000 bar, cycle 3 times to obtain a light yellow translucent suspension of nanoparticles with a particle size of 80-120 nm; Step STP140, spray drying: the nano suspension is mixed with a protective agent and then spray dried to form a dry powder with a particle size of ≤10 μm and an encapsulation rate of >95%, wherein the protective agent is a mixture of mannitol and trehalose, and the spray drying conditions are: inlet temperature 80-100°C, outlet air temperature 40-50°C; The method for preparing the light protection composite microcapsules comprises: Step STP210, core material emulsification: anthocyanidin, crocetin, and astaxanthin are mixed in a weight ratio of 20:1:0.8, 10% gum arabic aqueous solution is added, and high-speed shear emulsification is performed at 10,000 rpm for 10 minutes to obtain an emulsified solution; Step STP220, spray drying: drying the emulsified solution obtained in step STP210 under the conditions of an inlet air temperature of 160°C, an outlet air temperature of 80°C, and an atomization pressure of 0.3 MPa to obtain dark purple fluid powder microcapsules; The method for preparing the neuroinflammation regulating nanocrystals comprises: Step STP310, nanocrystal preparation: curcumin and Pluronic F127 were dissolved in acetone at a ratio of 1:3, dropped into ultrapure water and magnetically stirred for 24 hours, and the nanoparticle crystals were collected by centrifugation; Step STP320, dry mixing: uniformly mixing the boswellic acid, berberine and curcumin nanocrystals by a three-dimensional mixer at 30 rpm for 30 minutes to obtain an orange-red powder; The preparation method of the epigenetic activator powder comprises: freeze drying: sulforaphane and EGCG are mixed in a mass ratio of 1:6.7, dissolved in deionized water, pre-frozen at -80°C, and then placed in a 0.1 mbar environment for vacuum drying for 24 hours to obtain a light green loose powder; The preparation method of the microbiome synergistic sustained-release particles comprises: placing sodium butyrate core particles in a fluidized bed, spraying Eudragit® L100 with a weight of 5% of the total weight of the sodium butyrate core particles and Eudragit® FS30D with a weight of 10% of the total weight of the sodium butyrate core particles in sequence; then mixing GOS, arabinoxylan and the coated sodium butyrate core particles in a V-type mixer at 20 rpm for 15 minutes to obtain white to beige particles; Then, the photoprotective complex microcapsules, neuroinflammation regulating nanocrystals and microbiome synergistic sustained-release granules were wet granulated and then tableted to obtain a sustained-release layer; Finally, the mitochondrial targeting nanoparticles and epigenetic activator powder are directly compressed to obtain a quick-release layer and pressed together with the sustained-release layer or wrapped outside the sustained-release layer. Thus, a finished tablet nutritional composition is obtained. The material controlled-release structure adopts multi-layer coating technology. For example, quick-release coating: the outer layer uses a pH-sensitive polymer (such as Eudragit® EPO) that dissolves rapidly in gastric juice; sustained-release coating: the inner layer uses ethyl cellulose or liposomes to delay release through diffusion or dissolution mechanism; such a structural design can accurately realize the stratification, partial release and absorption of the active ingredients, and avoid the active ingredients being enzymatically hydrolyzed in the digestive tract at the same time, resulting in reduced effects.

[0017] The main raw materials involved in this example were obtained from commercial sources, and the main sources are as follows: SS-31 peptide was purchased from Nanjing Yuanpeptide Biotechnology Co., Ltd. 32 H 49 N 9 O 5 Coenzyme Q10 was obtained from Shanghai Pukang Coenzyme Q10 capsules; saffron acid was purchased in batches from Shanghai Jizhi Biochemical Technology Co., Ltd. and Yunnan Xili Biotechnology Co., Ltd.; boswellic acid was obtained from β-boswellic acid with a purity of 95% to 99% provided by Chengdu Purifa Technology Development Co., Ltd.; sulforaphane was obtained from C for scientific research provided by Munster (Chengdu) Biotechnology Co., Ltd. 6 HNOS 2 EGCG was a 98% pure laboratory white powder provided by Sichuan Weike-Chengdu Biological. Sodium butyrate was an online purchase product provided by Sichuan Huanxu Biotechnology Co., Ltd.

[0018] Embodiment 3: In this example, 8-week-old male C57BL / 6 mice were used for animal experiments. This model mouse is genetically stable and sensitive to oxidative damage, and is suitable for the study of vision loss experiments. The mice were purchased from Chengdu Dashuo Experimental Animal Co., Ltd. and were raised in an environment with a temperature of 22±2°C, a humidity of 50±10%, and a 12-hour light / dark cycle.

[0019] In this example, sodium iodate was used to establish a retinal degenerative disease model. The process is briefly described as follows: After purchasing mice, the mice were raised normally for one week, with a number of not less than 40 mice, and their health status was observed, and mice with obvious abnormalities were removed; after one week of adaptive feeding, 15 normal mice were intraperitoneally injected on the 8th day to establish a model. The modeling process is: First, NaIO 3Dissolved in physiological saline, the final concentration is 20 mg / mL, used immediately after preparation, and stored away from light; secondly, calculated at 35 mg / kg body weight (for example, a mouse weighs 22g, 0.035g / kg × 0.022kg = 0.77mg is required for injection, corresponding to a solution volume of 0.0385mL); finally, using an insulin syringe (29G needle), insert the needle at about 45° in the left lower abdomen of the mouse, avoiding the bladder, and slowly push the injection; 72 hours after injection, the apoptosis of the outer layer of the mouse retina theoretically reached near the peak. In order to further verify the modeling, histopathology was used to confirm the success of the modeling. The specific operation was to randomly select 3 model mice and 2 normal mice, and all of them were killed by spinal dislocation, that is, the mouse head was pressed down with the thumb and index finger of the left hand, and the mouse tail was grabbed with the right hand and pulled back hard to dislocate the cervical vertebrae, separate the spinal cord from the brainstem, and the mouse died immediately. The eyeballs of the model mice and normal mice were taken to make paraffin sections for HE staining. The number of cells in the outer nuclear layer of the retina was counted under a light microscope, and the decrease ratio of the average number of ONL cells in the model mice compared with the normal mice was calculated as shown in Table 1. The ratio of the number of cells in the model group and the normal control group is shown in Table 1.

[0020] From the above, it can be seen that the above-mentioned model mice have been successfully modeled and can be used for subsequent experiments.

[0021] The remaining 12 mice with successful modeling were marked in groups of 3 and recorded as model control group, low-dose treatment group, medium-dose treatment group and high-dose treatment group, a total of 4 groups, and 3 normal mice were selected for control, recorded as normal control group. The above 5 groups of mice were all fed by gavage. The preparation method of the nutritional composition was to mix the nutritional composition in Nutrition Example 1 with 0.5% sodium carboxymethyl cellulose, and vortex oscillation to make a uniform suspension; it was prepared on the spot and stored in the dark. If the nutritional composition prepared once needs to be used twice, it should be sealed and refrigerated at 4°C for no more than 24 hours. When gavage, it should be noted that the neck of the mouse should be fixed first, and the gavage needle should be inserted into the esophagus along the right side of the mouth with a 22G elbow to a depth of about 2-3cm. The injection speed is ≤0.1mL / s to avoid reflux or misentering the trachea. The drug was administered continuously for 28 days to cover the retinal repair cycle at the same time. The treatment scheme of each group is shown in the following table 2 for each group of mice:

[0022] After the dosing cycle is completed, all mice in each group are placed in a dark environment with a closed room away from light to allow all mice to adapt to the dark for 30-60 minutes; then the curtains are gradually opened to gradually increase the light in the room, and the gradual change from total darkness to natural light is completed within 15 minutes to avoid sudden strong light exposure to stimulate the mouse eyes; finally, all light sources in the room are turned off, and the cycle is repeated to allow the mice to adapt to the dark for 30 minutes.

[0023] The dark-adapted mice were then tested for visual function. The test method was to use the virtual optical oculomotor instrument OptoMotry-HD produced by Shanghai Yuanmai Biotechnology Co., Ltd. to test the mice. Specifically, the mice were fixed in the center of the platform, and the striped drum rotated at a speed of 12° / s. The spatial frequency gradually increased from 0.042 cycles / degree (cpd); the highest spatial frequency of the head tracking movement of the mice was recorded (unit: cpd, the higher the value, the better the vision); each mouse was tested 3 times, and the average value was taken, as shown in the OKR threshold list of each model group in Table 3 below.

[0024] As shown in Table 3 above, the OKR threshold of the normal control group is about 0.5 cpd, indicating that the visual function of the mice is normal; the OKR threshold of the model group is about 0.18 cpd, which is significantly lower than that of the normal control group, indicating that the vision is severely impaired after modeling; and the treatment group gradually recovers with the increase of dose, specifically low → medium → high: 0.25 → 0.35 → 0.45 cpd, that is, the high-dose group recovers to 85% of normal. Statistically significant low-dose group partially improved (p < 0.05), medium-dose group significantly recovered (p < 0.01), and high-dose group was close to normal (p < 0.001).

[0025] In summary, the multimodal targeted delivery nutritional composition for delaying vision loss prepared in Example 2 as described in Example 1 has a significant effect on delaying vision loss and restoring vision. The fundamental reason for its significant effect is that the mechanism of the active ingredient acting on the organism is fundamentally different from that of existing oral nutritional products or health products, as follows: The effective ingredients of the nutritional composition provided by the present invention mainly act at different levels from the tissue layer, cell layer and molecular layer, and finally achieve the effect of each component module on the biological vision. The following will analyze and explain each functional module of the targeted delivery nutritional composition provided by the present invention. Figure 1As shown, the digestion, absorption and mechanism of action of the nutrient composition described in this embodiment after oral administration of the organism can be roughly summarized as follows: oral ingestion of targeted nutrients, when passing through the digestive tract of the organism, dissolves and releases the effective ingredients in the digestive tract under the action of water and enzymes, wherein the quick-release layer disintegrates within 3 minutes, and the sustained-release layer continuously releases for 12 hours. The quick-release layer will be released in the stomach of the organism, and under the action of Eudragit® FS30D, since it will only dissolve at pH 7.0, it will not be released when it reaches the stomach of the organism, thereby effectively solving the problem of the effective ingredients being destroyed before reaching the designated site for absorption. Until reaching the small intestine and colon, it is mainly absorbed by the epithelial cells of the small intestine, and then delivered to the site of action through the blood circulation, and precipitated at the site of action, such as the retina; finally, it is released and activated in the cell, and combined with the target molecule to achieve the ultimate technical effect of delaying vision loss and protecting vision.

[0026] About mitochondrial targeted nanoparticles: Due to the use of targeted nanoparticle structure, a pre-modified carrier material can be used to pre-combine TPP with a polymer (such as PLGA, PEG) to form a TPP-polymer conjugate (such as TPP-PEG-PLGA); during the emulsification / solvent evaporation process, TPP-polymer is co-assembled with other materials to expose TPP on the surface of the nanoparticle. Surface modification of triphenylphosphine (TPP): The electrostatic adsorption of the mitochondrial membrane potential of -150 to -170 mV and the TPP cation is used to drive the nanoparticles to penetrate the mitochondrial double membrane; since the particle size of this embodiment is controlled at 80 nm-150 nm, it passively penetrates through the mitochondrial membrane pores, and the diameter of the mitochondrial membrane pores is about 200 nm, thereby achieving true targeted delivery. The lipid-soluble coenzyme Q10 is loaded in the nanoparticle core, and the efficiency of the electron transport chain is enhanced through the mitochondrial inner membrane complex, and ATP generation is increased; it can also be coated with superoxide dismutase mimics to neutralize superoxide free radicals O in mitochondria. 2 ⁻, the oxidative stress marker MDA is significantly reduced, achieving the purpose of clearing ROS; this makes the mitochondrial drug concentration 40 times higher than the cytoplasm, reducing systemic exposure, and simultaneously enhancing energy metabolism and antioxidant defense, which has a positive effect on degenerative diseases. Compared with existing nutrients, the mitochondrial targeted nanoparticles of the present invention solve the problem that the existing technology cannot effectively achieve targeted delivery due to absorption, digestion and excretion mainly through the digestive tract.

[0027] Regarding light-protective composite microcapsules: It is worth noting that the composite in the light-protective composite microcapsules in this embodiment is TiO 2-PLGA architecture, using sodium alginate-chitosan complex coacervate, pH=3.5 to form a gel, encapsulating lutein / zeaxanthin, extending the photodegradation half-life from 4h to 72h, and the lutein retention rate after outdoor use is >90%, with super photostability; the added nano-titanium dioxide particle size is only 20 nm, which can serve as a physical reflection layer, reducing UVA / UVB transmittance by 95%; the microcapsule surface is grafted with trypsin substrate polypeptide chains, which can release antioxidants such as astaxanthin after enzymatic hydrolysis of the skin stratum corneum, and targeted release at the site of photodamage, reducing the phototoxicity of normal tissues and achieving the effect of enzyme response release.

[0028] Regarding neuroinflammation regulating nanocrystals: First, the nanocrystal particle size is ≤100 nm, and PEG2000 modification reduces the capture of the mononuclear phagocytic system, and the distribution in brain tissue increases several times, achieving surface PEGylation; secondly, the drug-loaded curcumin nanocrystals significantly reduces the secretion of proinflammatory factors TNF-α and IL-6 by blocking the MyD88 adaptor protein, achieving the inhibition of TLR4 / NF-κB; thirdly, the co-loading of sulforaphane promotes the expression of antioxidant enzymes (HO-1, NQO1), and the proportion of M2 microglia will increase significantly, activating the Nrf2 pathway, thereby ultimately achieving microglial polarization regulation. In summary, neuroinflammation regulating nanocrystals can simultaneously achieve dual-pathway regulation of inhibiting inflammation and enhancing repair, increase the concentration of effective ingredients in the brain parenchyma far greater than the plasma concentration, and achieve true precision delivery.

[0029] About epigenetic activator powder: Sulforaphane covalently binds to the active sites of HDAC enzymes, such as HDAC1 / 2 / 3, through thiol groups, inhibiting deacetylation, resulting in increased histone H3 / H4 acetylation levels, chromatin opening, and promoting the transcription of antioxidant genes, such as NQO1 and HO-1. At the same time, by modifying the cysteine ​​residues of Keap1, Nrf2 is released to enter the cell nucleus, bind to the antioxidant response element (ARE), and activate downstream detoxification and antioxidant genes. Furthermore, sulforaphane metabolites, such as sulforaphane-glutathione conjugates, can be converted into active forms by intestinal flora, such as lactobacilli, to enhance local antioxidant effects. EGCG inserts into the active pocket of DNMT1 through the catechol group, blocking the methyl donor binding of S-adenosylmethionine (SAM) and reducing DNA methylation levels; further, by activating HATs such as p300 / CBP, histone H3K9 / K14 acetylation is increased, promoting the expression of anti-inflammatory genes. EGCG also has a synergistic effect on the microbiome. Specifically, EGCG regulates the structure of intestinal flora, inhibits pathogenic bacteria such as Escherichia coli, promotes probiotics such as Bifidobacterium, increases the abundance of SCFAs-producing bacteria, and indirectly enhances epigenetic regulation.

[0030] Regarding the microbiome synergistic sustained-release particles: First, PLGA particles are stable in gastric acid and slowly degrade in the intestinal alkaline environment (pH 7.4), releasing sulforaphane and EGCG to the colon, directly acting on intestinal epithelial cells and microbiota, and playing a role in targeted delivery; secondly, they avoid gastric acid and digestive enzymes from destroying sulforaphane (easy to oxidize) and EGCG (easy to polymerize and inactivate), and play a role in protecting the active ingredients. The above two points are also the main differences from the existing technology. In addition, sustained-release particles promote the proliferation of probiotics, such as Bifidobacterium, whose metabolite ‌butyrate‌ is itself an HDAC inhibitor, synergistically enhancing histone acetylation with sulforaphane, and propionate‌ activates the G protein-coupled receptor GPR43, inhibiting the NF-κB pathway, and synergistically reduces intestinal inflammation with the demethylation effect of EGCG, playing a bridging role of SCFAs.

[0031] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A nutritional composition for delaying vision loss based on multimodal targeted delivery, characterized in that: It includes mitochondrial targeted nanoparticles, photoprotective complex microcapsules, neuroinflammation regulating nanocrystals, epigenetic activator powder, and microbiome synergistic sustained-release particles; the mitochondrial targeted nanoparticles are composed of lutein, zeaxanthin, SS-31 peptide, and coenzyme Q10 in a weight ratio of 10:2:50:0.5; the photoprotective complex microcapsules are composed of anthocyanidins, crocetin, and astaxanthin in a weight ratio of 100:5:4; the neuroinflammation regulating nanocrystals are composed of boswellic acid, curcumin, and berberine in a weight ratio of 150:50:25; the epigenetic activator powder is composed of sulforaphane and EGCG in a weight ratio of 15:100; the microbiome synergistic sustained-release particles are composed of GOS, arabinoxylan, and sodium butyrate in a weight ratio of 50:300:

200.

2. A method for preparing a nutritional composition, for preparing a nutritional composition consisting of mitochondrial targeting nanoparticles, photoprotective complex microcapsules, neuroinflammation regulating nanocrystals, epigenetic activator powder, and microbiome synergistic slow-release particles, characterized in that: The preparation steps are as follows: The method for preparing mitochondrial targeting nanoparticles comprises: Step STP110, lipid film formation: Phosphatidylcholine, cholesterol and SS-31 peptide were dissolved in chloroform at a weight ratio of 7:2:1, and rotary evaporated at 40°C and 0.1 MPa to form a uniform film; Step STP120, active ingredient loading: lutein and zeaxanthin dissolved in anhydrous ethanol are mixed with coenzyme Q10 dissolved in olive oil, added into a phosphate buffer with pH = 7.4, and hydrated at 50°C for 1 hour; Step STP130, high pressure homogenization: using a high pressure homogenizer at 1000 bar, cycle 3 times to obtain a light yellow translucent suspension of nanoparticles with a particle size of 80-120 nm; Step STP140, spray drying: the nano suspension is mixed with a protective agent and then spray dried to form a dry powder with a particle size of ≤10 μm and an encapsulation rate of >95%, wherein the protective agent is a mixture of mannitol and trehalose, and the spray drying conditions are: inlet temperature 80-100°C, outlet air temperature 40-50°C; The method for preparing the light protection composite microcapsules comprises: Step STP210, core material emulsification: anthocyanidin, crocetin, and astaxanthin are mixed in a weight ratio of 20:1:0.8, 10% gum arabic aqueous solution is added, and high-speed shear emulsification is performed at 10,000 rpm for 10 minutes to obtain an emulsified solution; Step STP220, spray drying: drying the emulsified solution obtained in step STP210 under the conditions of an inlet air temperature of 160°C, an outlet air temperature of 80°C, and an atomization pressure of 0.3 MPa to obtain dark purple fluid powder microcapsules; The method for preparing the neuroinflammation regulating nanocrystals comprises: Step STP310, nanocrystal preparation: curcumin and Pluronic F127 were dissolved in acetone at a ratio of 1:3, dropped into ultrapure water and magnetically stirred for 24 hours, and the nanoparticle crystals were collected by centrifugation; Step STP320, dry mixing: uniformly mixing boswellic acid, berberine and curcumin nanocrystals by a three-dimensional mixer at 30 rpm for 30 minutes to obtain an orange-red powder; The preparation method of the epigenetic activator powder comprises: freeze drying: sulforaphane and EGCG are mixed in a mass ratio of 1:6.7, dissolved in deionized water, pre-frozen at -80°C, and then placed in a 0.1 mbar environment for vacuum drying for 24 hours to obtain a light green loose powder; The preparation method of the microbiome synergistic sustained-release particles comprises: placing sodium butyrate core particles in a fluidized bed, spraying Eudragit® L100 with a weight of 5% of the total weight of the sodium butyrate core particles and Eudragit® FS30D with a weight of 10% of the total weight of the sodium butyrate core particles in sequence; then mixing GOS, arabinoxylan and the coated sodium butyrate core particles in a V-type mixer at 20 rpm for 15 minutes to obtain white to beige particles; Then, the photoprotective complex microcapsules, neuroinflammation regulating nanocrystals and microbiome synergistic sustained-release granules were wet granulated and then tableted to obtain a sustained-release layer; Finally, the mitochondrial targeting nanoparticles and epigenetic activator powder are directly compressed to obtain a quick-release layer and then compressed together with the sustained-release layer or wrapped outside the sustained-release layer.

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