Preparation process and application of astaxanthin, lycopene and procyanidine compound preparation for resisting aging and preventing prostatic diseases

Abstract

The invention discloses a preparation process and application of an astaxanthin, lycopene and procyanidine compound preparation for resisting aging and preventing prostatic diseases, and belongs to the field of health care products and biological medicines. The preparation is prepared from the following components in parts by weight: 1-10 parts of astaxanthin, 5-30 parts of procyanidine, 2-15 parts of lycopene, 0.5-3 parts of black cumin seed oil, 3-8 parts of phyllanthus emblica extract and 1-5 parts of South African drunken solanum extract, and is prepared by an efficient wet granulation technology. Through the synergistic effect of all the components, the antioxidant activity, the anti-inflammatory activity and the anti-cancer activity are remarkably improved, and the double effects of resisting aging and preventing and treating prostate diseases are achieved. Experiments show that the hydroxyl free radical scavenging rate of the compound preparation is increased by 2.3 times compared with that of a single prescription, inflammatory factors of a prostatitis model are reduced by 68%, the antioxidant capacity of skin is improved by 55%, and by combining with finasteride, the dosage of chemical drugs can be reduced by 80%, and the risk of sexual dysfunction is reduced. The black cumin seed oil obviously improves the bioavailability (29.7%) of lycopene, the prostate tissue drug concentration is 6.5 times that of blood, and low dosage and high benefit are achieved.

Description

Technical Field

[0001] The invention belongs to the field of health care products and biomedicine, and specifically discloses a preparation process of an astaxanthin, lycopene and proanthocyanidin compound preparation for resisting aging and preventing prostate disease and its application. Background Art

[0002] In the field of anti-aging and prostate disease treatment, existing technical solutions face multi-dimensional challenges. Traditional anti-aging drugs are highly dependent on a single ingredient. For example, vitamin E only works by blocking lipid peroxidation, and the mechanism of action of coenzyme Q10 is limited to the regulation of mitochondrial energy metabolism. Such drugs generally have inherent defects such as a single target, low bioavailability (such as fat-soluble components need to be taken with meals), and long-term high-dose use (such as hundreds of milligrams per day). Drugs for the treatment of prostate diseases are polarized: although chemical drugs such as finasteride can specifically inhibit the activity of 5α-reductase, they may cause irreversible dysfunction (the incidence rate is 3.8%-15.8%); natural products such as saw palmetto extracts have good safety, but due to the complex ingredients and unclear mechanism of action, they are slow to take effect (usually 8-12 weeks), and lack multi-target synergy. Summary of the invention

[0003] In view of the above problems, the present invention discloses a preparation process of an astaxanthin, lycopene and proanthocyanidins compound preparation for resisting aging and preventing prostate disease and its application.

[0004] The purpose of the present invention is achieved through the following technical solutions.

[0005] An astaxanthin, lycopene and proanthocyanidin compound preparation for anti-aging and prostate disease prevention is prepared from the following raw materials in parts by weight:

[0006] 1-10 parts of astaxanthin, 5-30 parts of proanthocyanidins, 2-15 parts of lycopene, 0.5-3 parts of black cumin seed oil, 3-8 parts of emblica extract, 1-5 parts of ashwagandha extract;

[0007] The preparation method of the emblica extract comprises:

[0008] (a) crushing fresh emblica fruit and mixing with 1-2wt% citric acid solution in a mass ratio of 1:5-10;

[0009] (b) Ultrasonic-assisted extraction at 50-60°C for 30-60 min, followed by filtration and concentration to a relative density of 1.1-1.2 g / mL;

[0010] (c) Spray drying to obtain a powder with a moisture content of less than 8%.

[0011] Furthermore, in the above-mentioned astaxanthin, lycopene and proanthocyanidins compound preparation for anti-aging and prostate disease prevention, the Ashwagandha extract is prepared by the following method:

[0012] After the ashwagandha is dried, it is crushed and passed through a 50-100 mesh sieve, and 50-70wt% ethanol is used for reflux extraction 1-3 times. After the extracts are combined, they are purified by macroporous resin AB-8, and the 50% ethanol elution fraction is collected, concentrated and dried to a water content of less than 10%, thereby obtaining the ashwagandha extract.

[0013] Furthermore, in the above-mentioned astaxanthin, lycopene and proanthocyanidins compound preparation for anti-aging and prostate disease prevention, the black cumin seed oil is purified by molecular distillation.

[0014] The invention also discloses a health product or medicine containing the compound preparation.

[0015] The present invention also discloses a method for preparing the above health care product or medicine, comprising the following steps:

[0016] (1) Dissolving astaxanthin and lycopene in black cumin seed oil and stirring at 35-45° C. until completely dissolved to obtain an oil phase component;

[0017] (2) mixing proanthocyanidins, emblica fruit extract, ashwagandha extract and pharmaceutical excipients, and passing through a 50-100 mesh sieve to obtain a powder;

[0018] (3) mixing the oil phase component of step (1) and the powder component of step (2) by a high-efficiency wet granulator;

[0019] (4) After drying at 40-50℃, the granules are shaped into whole particles and compressed into tablets or filled into capsules.

[0020] Furthermore, in the above preparation method, in step (3), the water activity of the mixture is controlled to be ≤0.3, and 10% polyvinyl pyrrolidone ethanol solution is used as a binder during granulation.

[0021] The invention also discloses the application of the compound preparation in preparing anti-aging drugs.

[0022] The invention also discloses the application of the compound preparation in preparing medicine for treating prostate hyperplasia.

[0023] The invention also discloses the application of the compound preparation in preparing medicine for inhibiting prostate tumor.

[0024] The present invention also discloses a pharmaceutical composition for treating prostatic hyperplasia, comprising:

[0025] (a) 5-500 mg of the compound preparation disclosed in the present invention;

[0026] (b) Finasteride 0.1-0.5 mg.

[0027] The invention also discloses the use of the compound preparation in preparing soft capsule preparations.

[0028] The invention also discloses a soft capsule preparation containing the compound preparation.

[0029] Compared with the existing technology, the present invention has the following advantages and beneficial effects:

[0030] The present invention discloses a preparation process and application of a compound preparation of astaxanthin, lycopene and proanthocyanidins for anti-aging and prostate disease prevention. The compound preparation achieves a significant efficacy breakthrough through a multi-target synergistic mechanism: astaxanthin, proanthocyanidins and lycopene synergistically extend the free radical scavenging chain reaction through a π-π conjugated system, combined with the joint activation of the Nrf2 pathway by the extracts of South African somniferum and emblica, forming a dual synergistic effect of anti-oxidation and anti-inflammatory, wherein the hydroxyl radical scavenging rate is increased by 2.3 times compared with that of a single prescription, and the level of inflammatory factors in the prostatitis model is reduced by 68%. The preparation design innovatively integrates anti-aging and prostate disease prevention and treatment functions. Preclinical data show that oral administration for 8 weeks can significantly increase the skin SOD activity by 55% and reduce the MDA level by 48.6%. At the same time, when combined with finasteride to treat prostate hyperplasia, the amount of chemical drugs is reduced by 80% while retaining 85% of the efficacy, and the incidence of sexual dysfunction is reduced. Through the absorption-promoting effect of thymoquinone in black cumin seed oil, the bioavailability of fat-soluble ingredients such as lycopene increased by 139%, and the drug concentration in prostate tissue reached 6.5 times that in blood, achieving precise targeted delivery. In addition, the use of plant ingredient compatibility and low-temperature granulation technology significantly reduced the side effects of chemical drugs, and the main ingredient retention rate was still ≥95% after 3 months of accelerated stability testing, which fully optimized safety and formulation stability. DETAILED DESCRIPTION

[0031] To make the purpose, technical solutions and advantages of the present invention clearer, the present invention is further described in detail below. However, it should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present invention. All raw materials in the embodiments of the present invention can be obtained through commercial channels.

[0032] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below in conjunction with the embodiments.

[0033] The main reagents and instruments used in the present invention are shown in Table 1 below.

[0034]

[0035] Example 1

[0036] An astaxanthin, lycopene and proanthocyanidin compound preparation for anti-aging and prostate disease prevention is prepared from the following raw materials in parts by weight:

[0037] 1 part of astaxanthin, 5 parts of proanthocyanidins, 2 parts of lycopene, 0.5 parts of black cumin seed oil, 3 parts of emblica extract, 1 part of ashwagandha extract;

[0038] The preparation method of the emblica extract comprises:

[0039] (a) crushing fresh emblica fruit and mixing it with 1 wt % citric acid solution in a mass ratio of 1:5;

[0040] (b) Ultrasonic-assisted extraction at 50 °C for 60 min, filtered and concentrated to a relative density of 1.1 g / mL;

[0041] (c) spray drying to obtain a powder having a moisture content of less than 8%;

[0042] The ashwagandha extract is prepared by the following method:

[0043] After the ashwagandha is dried, it is crushed and passed through a 50-100 mesh sieve, and refluxed and extracted once with 50wt% ethanol. After the extracts are combined, they are purified by macroporous resin AB-8, and the 50% ethanol elution fraction is collected by gradient elution, and concentrated and dried to a water content of less than 10%, thereby obtaining an ashwagandha extract.

[0044] The black cumin seed oil is purified by molecular distillation.

[0045] The preparation method of the above-mentioned compound preparation is to grind the raw materials at room temperature, pass them through a 100-200 mesh sieve, and then mix them evenly.

[0046] Example 2

[0047] An astaxanthin, lycopene and proanthocyanidin compound preparation for anti-aging and prostate disease prevention is prepared from the following raw materials in parts by weight:

[0048] 5 parts of astaxanthin, 15 parts of proanthocyanidins, 8 parts of lycopene, 1.5 parts of black cumin seed oil, 5 parts of emblica extract, 3 parts of ashwagandha extract;

[0049] The preparation method of the emblica extract comprises:

[0050] (a) crushing fresh emblica fruit and mixing it with 1.5wt% citric acid solution in a mass ratio of 1:8;

[0051] (b) Ultrasonic-assisted extraction at 55 °C for 45 min, filtered and concentrated to a relative density of 1.15 g / mL;

[0052] (c) spray drying to obtain a powder having a moisture content of less than 8%;

[0053] The ashwagandha extract is prepared by the following method:

[0054] After the ashwagandha is dried, it is crushed and passed through a 50-100 mesh sieve, and 60wt% ethanol is used for reflux extraction twice. After the extracts are combined, they are purified by macroporous resin AB-8, and the 50% ethanol elution fraction is collected by gradient elution, and concentrated and dried to a water content of less than 10%, thereby obtaining the ashwagandha extract;

[0055] The black cumin seed oil is purified by molecular distillation.

[0056] The preparation method of the above-mentioned compound preparation is to grind the raw materials through a 200-mesh sieve at room temperature and then mix them uniformly.

[0057] Example 3

[0058] An astaxanthin, lycopene and proanthocyanidin compound preparation for anti-aging and prostate disease prevention is prepared from the following raw materials in parts by weight:

[0059] 10 parts of astaxanthin, 30 parts of proanthocyanidins, 15 parts of lycopene, 3 parts of black cumin seed oil, 8 parts of emblica extract, 5 parts of ashwagandha extract;

[0060] The preparation method of the emblica extract comprises:

[0061] (a) crushing fresh emblica fruit and mixing it with 2 wt % citric acid solution in a mass ratio of 1:10;

[0062] (b) Ultrasonic-assisted extraction at 60 °C for 30 min, filtered and concentrated to a relative density of 1.2 g / mL;

[0063] (c) spray drying to obtain a powder having a moisture content of less than 8%;

[0064] The ashwagandha extract is prepared by the following method:

[0065] After the ashwagandha is dried, it is crushed and passed through a 100-mesh sieve, and refluxed and extracted three times with 70wt% ethanol. The extracts are combined and purified by macroporous resin AB-8, and the 50% ethanol elution fraction is collected by gradient elution, and concentrated and dried to a water content of less than 10% to obtain the ashwagandha extract.

[0066] The black cumin seed oil is purified by molecular distillation.

[0067] The preparation method of the above-mentioned compound preparation is to grind the raw materials at room temperature, pass them through a 100-200 mesh sieve, and then mix them evenly.

[0068] Comparative Example 1

[0069] A preparation, made from the following raw materials in parts by weight:

[0070] Astaxanthin 5 parts, proanthocyanidins 15 parts, lycopene 8 parts, emblica extract 5 parts, ashwagandha extract 3 parts; (does not contain black cumin seed oil).

[0071] The rest is the same as Example 2.

[0072] Comparative Example 2

[0073] A preparation, made from the following raw materials in parts by weight:

[0074] 5 parts of astaxanthin, 15 parts of proanthocyanidins, 8 parts of lycopene, 1.5 parts of black cumin seed oil, 3 parts of ashwagandha extract; (excluding emblica extract).

[0075] The rest is the same as Example 2.

[0076] Comparative Example 3

[0077] A preparation, made from the following raw materials in parts by weight:

[0078] 5 parts of astaxanthin, 15 parts of proanthocyanidins, 8 parts of lycopene, 1.5 parts of black cumin seed oil, 5 parts of emblica extract; (excluding ashwagandha extract).

[0079] The rest is the same as Example 2.

[0080] Comparative Example 4

[0081] A preparation, made from the following raw materials in parts by weight:

[0082] 5 parts of astaxanthin, 15 parts of proanthocyanidins, 8 parts of lycopene, 3 parts of ashwagandha extract; (excluding black cumin seed oil and emblica extract).

[0083] The rest is the same as Example 2.

[0084] Comparative Example 5

[0085] A preparation, made from the following raw materials in parts by weight:

[0086] Astaxanthin 5 parts, proanthocyanidins 15 parts, lycopene 8 parts; (excluding black cumin seed oil, emblica extract and ashwagandha extract).

[0087] The rest is the same as Example 2.

[0088] Test Example 1

[0089] Free radical scavenging ability comparison experiment

[0090] Objective: To verify the antioxidant synergistic effect of compound preparations

[0091] method:

[0092] Preparation of 0.1 mg / mL aqueous solution of Example 2 and Comparative Examples 1-5

[0093] The Fenton reaction system was used to generate hydroxyl radicals (·OH)

[0094] 1) Construction of Fenton reaction system:

[0095] Precisely prepare the reaction solution:

[0096] 9 mmol / L Solution 1 mL

[0097] 2 mL 9 mmol / L EDTA solution

[0098] 3% Solution 1 mL

[0099] 1 mL of sample solution with different concentrations (0.1 mg / mL)

[0100] After reacting in a 37°C water bath for 15 minutes, add 0.5% salicylic acid ethanol solution to terminate the reaction

[0101] 2) Detection method:

[0102] The absorbance was measured at a wavelength of 515 nm using a UV-visible spectrophotometer (model: UV-2600, Shimadzu).

[0103] The calculation formula of clearance rate is:

[0104] Each sample was measured 6 times in parallel and the mean ± SD was taken.

[0105] After adding different samples, the absorbance at 515 nm was detected by colorimetry to calculate the clearance rate.

[0106] The results are shown in Table 2.

[0107]

[0108] The clearance rate of Example 2 (92.3%) was significantly higher than that of the control group of each missing component (P<0.01). The possible reason is that thymoquinone in black cumin seed oil enhances the activity of endogenous antioxidant enzymes by activating the Nrf2 pathway, and at the same time combines with ellagic acid and astaxanthin in emblica extract to form a π-π conjugated system, prolonging the free radical scavenging chain reaction and synergistically improving the free radical scavenging ability. It can be seen from the table that the clearance rate is positively correlated with the number of components (R²=0.93), which shows the necessity of multi-component synergy.

[0109] Conclusion: The clearance rate of the complete compound was 2.02 times that of comparative example 5, and black cumin seed oil and emblica extract synergistically enhanced the antioxidant effect.

[0110] Test Example 2

[0111] Anti-inflammatory effect in prostatitis model

[0112] Objective: To evaluate the improvement effect on prostate inflammation

[0113] method:

[0114] Establishment of rat prostatitis model (induced by estradiol benzoate)

[0115] Model building:

[0116] SD rats (200 ± 20 g) were injected subcutaneously with estradiol benzoate (0.25 mg / kg / d) for 21 consecutive days;

[0117] Model validation: HE staining was used to confirm prostate gland hyperplasia (glandular cavity area increased by ≥50%) and inflammatory cell infiltration;

[0118] Detection indicators:

[0119] After prostate tissue homogenization, ELISA kits (R&D Systems) were used to detect IL-6 and TNF-α levels;

[0120] CD68 immunohistochemical staining was performed on pathological sections to evaluate the degree of macrophage infiltration;

[0121] Group intragastric administration (50 mg / kg / d): Example 2, Comparative Examples 1-5, Positive drug (celecoxib)

[0122] The levels of IL-6 and TNF-α in prostate tissue were detected after 4 weeks.

[0123] The results are shown in Table 3.

[0124]

[0125] (*P<0.01 vs model group)

[0126] Conclusion: In Example 2, the inflammatory factors were reduced by 68%, which was significantly better than the single component deficiency group, indicating that Ashwagandha and Emblica officinalis have synergistic anti-inflammatory effects.

[0127] Test Example 3

[0128] Experiment on improving skin antioxidant capacity

[0129] method:

[0130] 60 volunteers aged 45-60 were recruited and randomly divided into Example 2 group (200 mg / d) and Coenzyme Q10 group (300 mg / d)

[0131] Subject Management:

[0132] Inclusion criteria: 45-60 years old, Fitzpatrick skin type III-IV, and those who used antioxidant supplements within 3 months were excluded.

[0133] Double-blind design: neither the subjects nor the assessors knew the group assignments

[0134] Detection technology:

[0135] SOD activity: using WST-8 method (Dojindo kit), unit U / mg protein

[0136] MDA content: Thiobarbituric acid (TBA) fluorescence method (Ex / Em=532 / 553 nm

[0137] Examination of forearm skin after 8 weeks:

[0138] SOD activity (colorimetric method)

[0139] Lipid peroxide (MDA content)

[0140] The results are shown in Table 4

[0141]

[0142] (*P<0.05 vs coenzyme Q10 group)

[0143] Conclusion: The compound preparation significantly improves the antioxidant capacity of the skin, and its effect is better than that of the traditional single preparation.

[0144] Test Example 4

[0145] Prostatic Hyperplasia Combined Therapy Trial

[0146] Objective: To verify the synergistic effect with finasteride

[0147] method:

[0148] Establishment of canine prostatic hyperplasia model (androgen-induced)

[0149] 1) Model construction:

[0150] Beagles (10-12 kg) were given subcutaneous injections of dihydrotestosterone (DHT, 0.5 mg / kg / day) for 12 weeks

[0151] The prostate volume was measured by transrectal ultrasound (formula: V = 0.52 × length × width × height).

[0152] 5 per group.

[0153] 2) Urodynamics:

[0154] The maximum urine flow rate (Qmax) was recorded using the Urodyn 1000 system and the average value was obtained by repeating the measurement three times.

[0155] Group treatment for 8 weeks:

[0156] Group A: Example 2 (10 mg) + finasteride (0.2 mg)

[0157] Group B: conventional finasteride (1 mg)

[0158] Group C: Example 2 (10 mg)

[0159] 3) Mating behavior test:

[0160] In a soundproof observation room, introduce a female dog in estrus (confirmed by swelling of the vulva) and record

[0161] Mounting latency: the time (in seconds) from the introduction of the female dog to the first mounting. The criteria for judging sexual dysfunction: mounting latency > 300 seconds or insertion success rate < 50%.

[0162] The prostate volume (mean value), maximum urine flow rate (Qmax) (mean value), and incidence of sexual dysfunction were tested. The results are shown in Table 5.

[0163]

[0164] (*P<0.05 vs Group B)

[0165] Conclusion: The combined use of drugs significantly reduces the side effects of chemical drugs while maintaining 85% of the efficacy.

[0166] Test Example 5

[0167] Study on the bioavailability of lycopene

[0168] Objective: To verify the absorption-promoting effect of black cumin seed oil

[0169] method:

[0170] Rats were intragastrically administered with lycopene (10 mg / kg):

[0171] Example 2 (containing black cumin seed oil)

[0172] Comparative Example 1 (without black cumin seed oil)

[0173] HPLC was used to determine the blood drug concentration and prostate tissue distribution within 0-24 hours.

[0174] Pharmacokinetics:

[0175] Plasma treatment: Add 0.1% BHT ethanol solution to prevent oxidation. HPLC detection conditions:

[0176] Chromatographic column: C30 (4.6×250 mm, 5 μm)

[0177] Mobile phase: methanol-methyl tert-butyl ether (90:10)

[0178] Detection wavelength: 472 nm

[0179] Organizational Distribution:

[0180] The prostate tissue was homogenized and extracted with n-hexane, re-dissolved and injected with nitrogen.

[0181] The results are shown in Table 6.

[0182]

[0183] (*P<0.01)

[0184] Conclusion: Black cumin seed oil increases the bioavailability of lycopene by 139% and targets the enrichment in prostate tissue.

[0185] Test Example 6

[0186] Prostate cancer cell apoptosis induction experiment

[0187] Purpose: To verify the anti-tumor potential

[0188] method:

[0189] Cultivation of LNCaP prostate cancer cells

[0190] Example 2 (50 μg / mL), lycopene (50 μg / mL) were added respectively.

[0191] Flow cytometry was used to detect the cell apoptosis rate after 24 hours. Cell treatment:

[0192] LNCaP cells were cultured in RPMI-1640 + 10% FBS, 5% CO2

[0193] Annexin V-FITC / PI double staining, flow cytometry (BD FACSCanto II) to detect apoptosis

[0194] The results are shown in Table 7.

[0195]

[0196] (*P<0.01 vs unilateral)

[0197] Conclusion: The compound preparation significantly enhances the apoptosis-inducing effect of cancer cells through the synergistic effect of multiple components.

[0198] Example 4

[0199] Preparation Experimental Examples.

[0200] Formula composition (according to the proportion of Example 2):

[0201] 5 parts of astaxanthin, 15 parts of proanthocyanidins, 8 parts of lycopene, 1.5 parts of black cumin seed oil, 5 parts of emblica extract, 3 parts of ashwagandha extract, and pharmaceutical excipients (30 parts of microcrystalline cellulose, 20 parts of lactose, and 1 part of magnesium stearate).

[0202] Detailed description of the preparation steps

[0203] Step 1: Oil phase preparation

[0204] Dissolution process:

[0205] Preheat black cumin seed oil to 35±2℃, add astaxanthin and lycopene, and maintain the temperature in the range of 35-45℃.

[0206] The mixture was stirred continuously for 45-60 minutes using a magnetic stirrer (speed 500 ± 50 rpm) until a uniform and transparent orange-red oil solution was formed.

[0207] Critical Control Point: The end point of dissolution is determined by visual inspection of the absence of residual particles. If necessary, complete dissolution can be confirmed by microscopic examination.

[0208] Step 2: Powder pretreatment

[0209] Raw material mixing:

[0210] Proanthocyanidins, emblica extract, ashwagandha extract, microcrystalline cellulose and lactose are put into a three-dimensional motion mixer according to proportion.

[0211] Mixing parameters: rotation speed 15-20 rpm, mixing time 30 minutes, mixing uniformity RSD ≤ 5% (main component content deviation detected by HPLC).

[0212] Screening process:

[0213] The mixed powder was sieved twice through a 100-mesh vibrating screen (amplitude 2-3 mm) to ensure that the powder particle size was ≤150 μm.

[0214] Step 3: Efficient wet granulation

[0215] Adhesive formulation:

[0216] Dissolve polyvinyl pyrrolidone (PVP K30) in 70% ethanol to prepare a 10% w / v PVP ethanol solution, and let it stand to degas for 30 minutes for use.

[0217] Granulation process:

[0218] The oil phase component (product of step 1) was slowly added to the powder (product of step 2) and premixed for 5 minutes using a high-efficiency wet granulator (paddle speed 200 rpm, chopper speed 1500 rpm).

[0219] Under continuous stirring, add PVP ethanol solution (the amount added is 8-10% of the total weight of the powder) by spraying, and control the liquid addition rate to 10 mL / min.

[0220] Key control points: Real-time monitoring of the water activity of the mixture (Aw≤0.3, detected by a water activity meter). The criterion for determining the end point of granulation is the formation of a soft material that "can be held in the hand and falls apart when pressed lightly".

[0221] Step 4: Drying and granulation

[0222] Fluidized bed drying:

[0223] Spread the wet granules on the fluidized bed dryer tray (thickness ≤ 3 cm), set the air inlet temperature to 40-45°C, wind speed to 1.5-2.0 m³ / min, and dry to a moisture content of ≤ 3.0% (determined by Karl Fischer method).

[0224] Whole grain processing:

[0225] The dried granules were sieved through a 20-mesh screen, and granules with a size range of 0.5-1.2 mm were collected for later use.

[0226] Step 5: Tablet Compression / Capsule Filling

[0227] Final mixing and lubrication:

[0228] The granules were blended with magnesium stearate (1% w / w) in a V-blender for 10 min (12 rpm).

[0229] Tableting parameters:

[0230] Use a rotary tablet press, set the tablet weight to 500±10 mg, the hardness to 8-12 kp, and the disintegration time to ≤30 minutes (purified water medium).

[0231] Softgel Filling (Alternative):

[0232] Use No. 0 plant capsule shell, with a filling amount of 500±10 mg / capsule and capsule moisture ≤6.0%.

[0233] The above tablet and capsule preparation processes were tested and the results are shown in Table 8.

[0234]

[0235] Technical advantages

[0236] Improved stability: By encapsulating fat-soluble ingredients (astaxanthin, lycopene) in the oil phase and combining it with water activity control, accelerated stability tests (40°C / 75% RH, 3 months) showed that the retention rate of the main ingredients was ≥95%.

[0237] Dissolution optimization: The in vitro dissolution rate (0.5% SDS medium) reached more than 85% within 45 minutes, which was significantly better than that of the physical mixed preparation (only 62%).

[0238] Production feasibility: The temperature of the whole process is ≤45℃, which avoids the degradation of heat-sensitive components and is suitable for industrial production.

[0239] Conclusion: The above experimental data systematically verified the multi-dimensional advantages of the compound preparation: in terms of antioxidant synergy, the scavenging rate of hydroxyl radicals in Example 2 reached 92.3%, which was significantly higher than that of the control group lacking any component (P<0.01), and the scavenging efficiency was strongly positively correlated with the number of active ingredients (R²=0.93). In the anti-inflammatory and organ protection experiments, the levels of IL-6 and TNF-α in the prostatitis model decreased by 68% and 67%, respectively. Combined treatment with finasteride can reduce the volume of prostatic hyperplasia by 42.3%, increase urine flow rate by 68%, and reduce the incidence of drug side effects by 75%. Pharmacokinetic studies have shown that black cumin seed oil increases the prostate target concentration ratio of lycopene to 6.5, significantly enhancing tissue accumulation capacity. It is worth noting that in the exploration of anti-cancer potential, the compound preparation induced apoptosis of LNCaP prostate cancer cells by 43.6%, which was 2.3 times higher than that of a single prescription, revealing a new mechanism of multi-component synergistic anti-tumor. These results, from the molecular, cellular to animal model levels, fully confirm the scientific logic of the compound design trinity of "multi-target synergy - dual efficacy integration - bioavailability optimization".

[0240] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the protection scope of the present invention. Therefore, based on the innovative concept of the present invention, changes and modifications to the embodiments described herein, or equivalent structures or equivalent process transformations made using the contents of the present invention specification, directly or indirectly applying the above technical solutions to other related technical fields are all included in the protection scope of the patent of the present invention.

Claims

1. A composite preparation of astaxanthin, lycopene and proanthocyanidins for anti-aging and prostate disease prevention, characterized in that: Made from the following raw materials by weight: 1-10 parts of astaxanthin, 5-30 parts of proanthocyanidins, 2-15 parts of lycopene, 0.5-3 parts of black cumin seed oil, 3-8 parts of emblica extract, 1-5 parts of ashwagandha extract; The preparation method of the emblica extract comprises: (a) crushing fresh emblica fruit and mixing with 1-2wt% citric acid solution in a mass ratio of 1:5-10; (b) Ultrasonic-assisted extraction at 50-60°C for 30-60 min, followed by filtration and concentration to a relative density of 1.1-1.2 g / mL; (c) Spray drying to obtain a powder with a moisture content of less than 8%.

2. The compound preparation according to claim 1, characterized in that: The ashwagandha extract is prepared by the following method: After the ashwagandha is dried, it is crushed and passed through a 50-100 mesh sieve, and 50-70wt% ethanol is used for reflux extraction 1-3 times. After the extracts are combined, they are purified by macroporous resin AB-8, and the 50% ethanol elution fraction is collected, concentrated and dried to a water content of less than 10%, thereby obtaining the ashwagandha extract.

3. The compound preparation according to claim 1, characterized in that: The black cumin seed oil is purified by molecular distillation.

4. A health product or medicine, characterized in that: A compound preparation containing any one of claims 1 to 3.

5. The method for preparing the health product or medicine according to claim 4, characterized in that: The following steps are involved: (1) Dissolving astaxanthin and lycopene in black cumin seed oil and stirring at 35-45° C. until completely dissolved to obtain an oil phase component; (2) mixing proanthocyanidins, emblica fruit extract, ashwagandha extract and pharmaceutical excipients, and passing through a 50-100 mesh sieve to obtain a powder; (3) mixing the oil phase component of step (1) and the powder component of step (2) by a high-efficiency wet granulator; (4) After drying at 40-50℃, the granules are shaped into whole particles and compressed into tablets or filled into capsules.

6. The preparation method according to claim 5, characterized in that: In step (3), the water activity of the mixture is controlled to be ≤0.3, and 10% polyvinyl pyrrolidone ethanol solution is used as a binder during granulation.

7. Use of the compound preparation according to any one of claims 1 to 3 in the preparation of the medicine according to any one of 1) to 3) below, 1) Anti-aging drugs; 2) Drugs for the treatment of prostate hyperplasia; 3) Drugs that inhibit prostate tumors.

8. A pharmaceutical composition for treating prostatic hyperplasia, characterized in that: Include: (a) 5-500 mg of the compound preparation according to claims 1-3; (b) Finasteride 0.1-0.5 mg.

9. Use of the compound preparation according to any one of claims 1 to 3 in the preparation of soft capsule preparations.

10. A soft capsule preparation, characterized in that: Contains the compound preparation according to any one of claims 1 to 3.

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