Application of polyphenol in preparation of medicine for preventing or treating prostatitis

Abstract

The invention discloses application of polyphenol in preparation of a medicine for preventing or treating prostatitis, and particularly relates to the technical field of medicines.The polyphenol comprises quercetin, chlorogenic acid, anthocyanin and chicoric acid in a purple-leaf lettuce extract and further comprises tea polyphenol, resveratrol, lycopene, soy isoflavone, curcumin and pomegranate polyphenol; the synergistic effect of all the components is shown as follows: the quercetin improves inflammation symptoms by inhibiting expression of TNF-alpha and IL-6 inflammatory factors in prostate tissues. By utilizing the synergistic effect of the polyphenol component, the composition can be used for preventing or treating prostatitis, improving prostate symptoms and maintaining hormone balance, not only can cope with the inflammation problem, but also can generate positive influence on hormone level, cell proliferation and the like, delay prostate cancer progression and the like, can adjust the dosage scheme according to the requirements of different patients, and has a good application prospect. A scientific basis is provided for individualized treatment of prostatitis, and the treatment requirements of patients with different illness states and different physiques can be better met.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine, more particularly, the present application relates to the application of polyphenols in the preparation of drugs for preventing or treating prostatitis. BACKGROUND

[0002] Prostatitis is a common male urological disease that seriously affects the quality of life of patients. According to the Chinese male disease diagnosis and treatment guidelines, the cure standard of prostatitis has been upgraded to a "four-dimensional assessment system", including symptom relief, normal examination index, image result improvement and long-term non-recurrence. Among them, the incidence of chronic prostatitis in adult men is quite high, and 2-10% of adult men are long-term sufferers, and it may increase the risk of prostate hyperplasia and prostate cancer.

[0003] Existing drugs mostly rely on a single active ingredient, and the mechanism of action is single, which is difficult to comprehensively respond to multiple pathological factors such as inflammation, hormone disorder and oxidative damage. For example, a single polyphenol can only play a role in anti-inflammatory or antioxidant, etc. in a certain aspect, and cannot improve the comprehensive pathological state of the prostate tissue. At the same time, the synergistic effect of drug combination in the existing treatment scheme is not fully utilized. The combination scheme of non-steroidal anti-inflammatory drugs, 5α-reductase inhibitors and other drugs often leads to insignificant enhancement of efficacy and even increases the risk of adverse reactions due to the conflict between components or unreasonable proportioning. Polyphenolic components are easily degraded in the gastrointestinal tract and are difficult to target the prostate-related parts, resulting in low bioavailability and limited efficacy. At the same time, the existing preparations do not consider improving the absorption efficiency through intestinal flora regulation or bioavailability enhancers. The inflammation degree, hormone level and body tolerance of different patients are different, and it is impossible to adjust the component proportion and dosage according to individual needs. SUMMARY

[0004] In order to overcome the above-mentioned defects of the prior art, the present application provides the application of polyphenols in the preparation of drugs for preventing or treating prostatitis, to solve the problems raised in the background art.

[0005] In order to achieve the above-mentioned purpose, the present application provides the following technical scheme: the application of polyphenols in the preparation of drugs for preventing or treating prostatitis, the polyphenols comprising quercetin, chlorogenic acid, anthocyanin and chicoric acid in lettuce extract, and also including tea polyphenols, resveratrol, lycopene, soy isoflavones, curcumin and pomegranate polyphenols; the synergistic effect of each component is as follows:

[0006] Quercetin improves inflammatory symptoms by inhibiting the expression of TNF-α and IL-6 inflammatory factors in prostate tissue;

[0007] Chlorogenic acid maintains stable hormone levels by regulating 5α-reductase activity;

[0008] Anthocyanins reduce prostate tissue damage by scavenging free radicals and inhibiting oxidative stress;

[0009] Chicoric acid enhances anti-inflammatory effects by inhibiting inflammatory signaling pathways;

[0010] Tea polyphenols synergize anti-inflammatory effects by inhibiting prostate cell over-proliferation and regulating immune function;

[0011] Resveratrol induces cancer cell apoptosis and inhibits inflammatory signaling pathways;

[0012] Soy isoflavones regulate hormone balance and inhibit 5α-reductase;

[0013] Curcumin inhibits prostate cancer cell metastasis through anti-inflammatory and antioxidant effects;

[0014] Pomegranate polyphenols delay prostate cancer progression by inhibiting androgen receptor activity.

[0015] Preferably, the medicine is an oral preparation that achieves targeted release of polyphenols in the colon through a sustained-release dosage form, and the medicine is used in combination with non-steroidal anti-inflammatory drugs or 5α-reductase inhibitors to synergistically enhance therapeutic effects.

[0016] Preferably, the total polyphenols in the red-leaf lettuce extract are 20-200 mg, including 30-50% quercetin, 15-35% chlorogenic acid, 10-30% anthocyanins, and 10-20% chicoric acid.

[0017] Preferably, the medicine further comprises probiotics for regulating intestinal flora to enhance the bioavailability of polyphenols, and the probiotics are Lactobacillus or Bifidobacterium, added in an amount of 1×10^8-1×10^10 CFU / dose.

[0018] Preferably, the medicine further comprises a bioavailability enhancer.

[0019] Preferably, the bioavailability enhancer is piperine.

[0020] Preferably, the medicine is used for preventing or treating prostate inflammation, improving prostate symptoms, and maintaining hormone balance.

[0021] Preferably, the red-leaf lettuce extract is prepared by the following steps:

[0022] (1) Fresh red-leaf lettuce stems and leaves are separated, the leaves are cut into sections, and then vacuum freeze-dried, pulverized to 80-120 mesh, and obtained as lettuce powder;

[0023] (2) The lettuce powder is mixed with an acidic ethanol solution (containing 40-60% ethanol and 0.1% ascorbic acid) at pH 4-5 at a ratio of 1:15-1:25 (g / mL), and extracted through dynamic countercurrent extraction at 50°C for 2 times, 45 minutes each time;

[0024] (3) The extraction solution is combined, the extraction solution is removed of macromolecular impurities by ceramic membrane ultrafiltration (10 kDa molecular weight cut-off), and the filtrate is adsorbed by a polyamide column;

[0025] (4) The sugar impurities are eluted with deionized water first, and then the target polyphenol is desorbed with a phosphate buffer solution at pH 7.4, the desorption solution is collected and freeze-dried to obtain the purple lettuce extract.

[0026] Technical effects and advantages of the present application:

[0027] 1. Through the synergistic effect of multiple polyphenol components, the efficacy is exerted from different mechanisms, quercetin inhibits inflammatory factors, chlorogenic acid maintains hormone stability, and anthocyanins reduce tissue damage, etc. Each component cooperates with each other, compared with a single polyphenol, it can more comprehensively cope with prostatitis and related problems, and the drug can be used in combination with non-steroidal anti-inflammatory drugs or 5 alpha-reductase inhibitors to further synergistically enhance the efficacy, which can more effectively improve the symptoms of prostatitis, and through adjusting the content of each component, individualized treatment can be realized, which can meet the needs of people sensitive to hormone levels, such as middle-aged and elderly patients, avoid hormone abnormalities, and also can be aimed at patients with severe symptoms or young patients to further improve the effect of symptom improvement, and give consideration to efficacy and safety, by controlling the content range of each component and the daily dose of total polyphenol, the symptoms can be significantly improved while avoiding abnormal fluctuations in hormone levels, reducing the possibility of adverse reactions, and it is suitable for long-term use or special groups;

[0028] 2. The appropriate dose range of each polyphenol component is determined, through precise component control, the risk caused by improper dose can be avoided while ensuring efficacy, the total polyphenol of purple lettuce 75 mg or more per day can significantly improve the IPSS score, increasing the dose or adjusting the proportion of specific components can further enhance the effect, while only accompanied by slight prolactin changes, the safety is higher, the drug is an oral preparation, the polyphenol is released in the colon by a sustained-release dosage form, which is beneficial to the polyphenol to play a role in the lesion-related part, improve the bioavailability and treatment specificity, the drug contains probiotics and bioavailability enhancers, the probiotics can regulate intestinal flora and enhance the bioavailability of polyphenols, thereby better exerting the drug efficacy;

[0029] 3. In summary, through the mutual influence of the above multiple effects, it can be used for preventing or treating prostatitis, improving prostate symptoms and maintaining hormone balance, not only can cope with inflammation problems, but also can have a positive impact on hormone levels, cell proliferation, etc. to delay the progression of prostate cancer, etc. The dose regimen can be adjusted according to the needs of different patients, which provides a scientific basis for individualized treatment of prostatitis, and can better meet the treatment needs of patients with different conditions and different constitutions. DETAILED DESCRIPTION

[0030] All other embodiments obtained by those of ordinary skill in the art without creative work on the basis of the embodiments of the present application fall within the scope of protection of the present application.

[0031] The dose-effect relationship of each component in the purple lettuce extract (purple lettuce is all Flora No. 1 purple lettuce) is explained in detail through multiple sets of control experiments, and the synergistic effect of improving the symptoms of prostatitis (taking IPSS score as an index, IPSS is international prostate symptom score) and the influence on prolactin level is verified. All experiments follow the principles of randomization, double-blind, placebo control, and the experimental subjects are patients with diagnosed chronic prostatitis (IPSS baseline score 15-30 points), serum prolactin level (normal reference value: male 4.04-15.2 ng / mL), and the sample size of each group is 30, and the treatment course is 8 weeks.

[0032] Example 1: Quercetin

[0033] Quercetin derived from purple lettuce extract 75 mg / day, and tea polyphenol 50 mg / day, resveratrol 40 mg / day, lycopene 25 mg / day, soy isoflavone 30 mg / day, curcumin 30 mg / day, and pomegranate polyphenol 30 mg / day are used, and the dosage form is a colon-targeted sustained-release capsule.

[0034] Example 2: Chlorogenic acid

[0035] Chlorogenic acid derived from purple lettuce extract 75 mg / day, and tea polyphenol 50 mg / day, resveratrol 40 mg / day, lycopene 25 mg / day, soy isoflavone 30 mg / day, curcumin 30 mg / day, and pomegranate polyphenol 30 mg / day are used, and the dosage form is a colon-targeted sustained-release capsule.

[0036] Example 3: Anthocyanin

[0037] Anthocyanin derived from purple lettuce extract 75 mg / day, and tea polyphenol 50 mg / day, resveratrol 40 mg / day, lycopene 25 mg / day, soy isoflavone 30 mg / day, curcumin 30 mg / day, and pomegranate polyphenol 30 mg / day are used, and the dosage form is a colon-targeted sustained-release capsule.

[0038] Example 4: Chrysanthemum acid

[0039] Chrysanthemum acid derived from purple lettuce extract 75 mg / day, and tea polyphenol 50 mg / day, resveratrol 40 mg / day, lycopene 25 mg / day, soy isoflavone 30 mg / day, curcumin 30 mg / day, and pomegranate polyphenol 30 mg / day are used, and the dosage form is a colon-targeted sustained-release capsule.

[0040] Example 5: Mixed group

[0041] The total polyphenols of purple lettuce extract include quercetin, chlorogenic acid, anthocyanin, and chicoric acid. The total polyphenols of purple lettuce extract are mixed at a ratio of quercetin: chlorogenic acid: anthocyanin: chicoric acid = 20%:20%:30%:30%. The total polyphenols of purple lettuce extract are 75 mg / day, and tea polyphenols 50 mg / day, resveratrol 40 mg / day, lycopene 25 mg / day, soy isoflavones 30 mg / day, curcumin 30 mg / day, and pomegranate polyphenols 30 mg / day. The dosage form is a colon-targeted sustained-release capsule.

[0042] Example 6: Purple lettuce powder

[0043] The total polyphenols of purple lettuce powder are more than 4%. The total polyphenols of purple lettuce powder are 75 mg / day, and the total polyphenols of purple lettuce powder include but are not limited to quercetin, chlorogenic acid, anthocyanin, and chicoric acid. The total polyphenols of purple lettuce powder are mixed at a ratio of quercetin: chlorogenic acid: anthocyanin: chicoric acid = 20%:20%:30%:30%. The total polyphenols of purple lettuce powder are 75 mg / day, and tea polyphenols 50 mg / day, resveratrol 40 mg / day, lycopene 25 mg / day, soy isoflavones 30 mg / day, curcumin 30 mg / day, and pomegranate polyphenols 30 mg / day. The dosage form is a colon-targeted sustained-release capsule.

[0044] Example 7: Purple lettuce extract

[0045] The total polyphenols of purple lettuce extract are more than 4%. The total polyphenols of purple lettuce extract are 75 mg / day, and the total polyphenols of purple lettuce extract include but are not limited to quercetin, chlorogenic acid, anthocyanin, and chicoric acid. The total polyphenols of purple lettuce extract are mixed at a ratio of quercetin: chlorogenic acid: anthocyanin: chicoric acid = 20%:20%:30%:30%. The total polyphenols of purple lettuce extract are 75 mg / day, and tea polyphenols 50 mg / day, resveratrol 40 mg / day, lycopene 25 mg / day, soy isoflavones 30 mg / day, curcumin 30 mg / day, and pomegranate polyphenols 30 mg / day. The dosage form is a colon-targeted sustained-release capsule. The comparison table of example experiments is as follows:

[0046]

[0047] The above examples show that the basic improvement effect of a single active ingredient, and the single component in the four kinds of purple lettuce extract, quercetin, chlorogenic acid, anthocyanin, and chicoric acid, can effectively improve the IPSS score of patients with chronic prostatitis (the score after treatment is reduced by about 5-7 points compared with the baseline), and reduce the serum prolactin level (an average of 3.2-4.2 ng / mL), indicating that these components are important basic substances for physiological activity;

[0048] The mixture group of Example 5 (quercetin: chlorogenic acid: anthocyanin: chicoric acid = 20%:20%:30%:30%) showed the best effect in two indicators, with IPSS score reduced by 11.7 points and prolactin level reduced by 6.7 ng / mL, far superior to the single component group, fully proving that the multi-component synergistic effect can greatly enhance the effect of improving prostate inflammation symptoms and regulating prolactin level, and embodies the superposition advantage.

[0049] The advantage of the extract form is highlighted, and the effect of red-leaf lettuce extract (Example 7) is better than that of red-leaf lettuce powder (Example 6), with IPSS score reduced by 1.2 points and prolactin level reduced by 0.6 ng / mL, which shows that the enrichment of total polyphenols (content > 4%) through the extraction process can reduce the interference of inactive ingredients, improve the bioavailability of active ingredients, and enhance the clinical effect.

[0050] The clinical application value is clear, and all examples containing red-leaf lettuce source components are better than the natural disease course, among which the mixed group and the extract group are particularly outstanding, providing a safe and effective natural component solution for the adjuvant treatment of chronic prostatitis, especially suitable for patients who need to improve urination symptoms and regulate hormone levels, embodying the multi-component synergistic advantage, and the present application can accurately adjust the dose according to the clinical needs, providing a basis for individualized treatment of prostatitis.

[0051] The above only describes the preferred embodiments of the present application and is not used to limit the present application, and any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. The application of polyphenols in the preparation of drugs for the prevention or treatment of prostatitis, characterized in that: The polyphenols include quercetin, chlorogenic acid, anthocyanins, and chicoric acid from purple lettuce extract, as well as tea polyphenols, resveratrol, lycopene, soy isoflavones, curcumin, and pomegranate polyphenols; the synergistic effect of each component is as follows: Quercetin improves inflammatory symptoms by inhibiting the expression of TNF-α and IL-6 inflammatory factors in prostate tissue; Chlorogenic acid maintains stable hormone levels by regulating 5α-reductase activity; Anthocyanins reduce prostate tissue damage by scavenging free radicals and inhibiting oxidative stress. Chicoric acid enhances anti-inflammatory effects by inhibiting inflammatory signaling pathways; Tea polyphenols work synergistically to reduce inflammation by inhibiting excessive proliferation of prostate cells and regulating immune function; Resveratrol inhibits inflammatory signaling pathways by inducing apoptosis in cancer cells; Soy isoflavones regulate hormone balance and inhibit 5α-reductase; Curcumin inhibits the metastasis of prostate cancer cells through its anti-inflammatory and antioxidant effects; Pomegranate polyphenols slow the progression of prostate cancer by inhibiting androgen receptor activity.

2. The use of the polyphenol according to claim 1 in the preparation of drugs for the prevention or treatment of prostatitis, characterized in that: The drug is an oral formulation that achieves targeted release of polyphenols in the colon through a sustained-release formulation. The drug is used in combination with nonsteroidal anti-inflammatory drugs or 5α-reductase inhibitors to synergistically enhance efficacy.

3. The use of the polyphenol according to claim 1 in the preparation of drugs for the prevention or treatment of prostatitis, characterized in that: The total polyphenols in the purple lettuce extract are 20-200 mg, including 30-50% quercetin, 15-35% chlorogenic acid, 10-30% anthocyanins, and 10-20% chicoric acid.

4. The use of the polyphenol according to any one of claims 1-3 in the preparation of a drug for the prevention or treatment of prostatitis, characterized in that: The drug also contains probiotics to regulate the intestinal flora and enhance the bioavailability of polyphenols. The probiotics are lactobacilli or bifidobacteria, and the amount added is 1×10^8-1×10^10 CFU / dose.

5. The use of the polyphenol according to any one of claims 1-5 in the preparation of a drug for the prevention or treatment of prostatitis, characterized in that: The drug also contains a bioavailability enhancer.

6. The use of the polyphenol according to any one of claims 1-6 in the preparation of a drug for the prevention or treatment of prostatitis, characterized in that: The bioavailability enhancer is piperine.

7. The use of the polyphenol according to any one of claims 1-7 in the preparation of a drug for the prevention or treatment of prostatitis, characterized in that: The drug is used to prevent or treat prostatitis, improve prostate symptoms, and maintain hormone balance.

8. The use of the polyphenol according to any one of claims 1-8 in the preparation of a drug for the prevention or treatment of prostatitis, characterized in that: The purple lettuce extract was prepared through the following steps: (1) Separate the stems and leaves of fresh purple lettuce, cut the leaves into sections, freeze-dry them under vacuum, and pulverize them to 80-120 mesh to obtain lettuce powder; (2) Mix lettuce powder with an acidic ethanol solution of pH 4-5 (containing 40-60% ethanol and 0.1% ascorbic acid) at a ratio of 1:15-1:25 (g / mL), and extract twice under dynamic countercurrent at 50℃ for 45 minutes each time; (3) Combine the extracts, and remove macromolecular impurities by ultrafiltration of the extracts through a ceramic membrane (molecular weight cutoff of 10kDa). The filtrate is then adsorbed through a polyamide column. (4) First, wash away sugar impurities with deionized water, then desorb the target polyphenols with phosphate buffer at pH 7.4, collect the desorbed solution and freeze-dry it to obtain purple lettuce extract.

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