Taraxacum triterpenoid composition for treating benign prostatic hyperplasia as well as preparation method and application of dandelion triterpenoid composition
A drug for the treatment of prostate hyperplasia was prepared by triterpene compositions in dandelions, including dandelion sterol, dandelion sterol acetate, lupinol and beta-fragranceolol, which resolved the complications of existing treatments and Adverse reaction problems have achieved safe and efficient treatment effects.
Patent Information
- Application Number
- CN202411340089.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-25
- Publication Date
- 2024-12-24
AI Technical Summary
Existing treatments for prostate hyperplasia, such as surgery and medication, have complications and adverse reactions, and have an impact on the elderly and quality of life, and lack safe and effective natural treatment options.
By screening out triterpene compositions in dandelions, including dandelion sterol, dandelion sterol acetate, lupinol and β-vinyl alcohol, it was prepared by ethanol extraction and chromatography column elution separation methods, and was used to prepare drugs for the treatment of prostate hyperplasia. .
This triterpene composition can significantly improve prostate hyperplasia, reduce prostate index and epithelial thickness, reduce collagen deposition, and show good therapeutic effects by inhibiting inflammatory response and regulating androgen balance.
Smart Images
Figure CN119174770A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of biomedicine, and particularly relates to a dandelion triterpene composition for treating prostate hyperplasia, and a preparation method and application thereof. Background Art
[0002] Benign prostate hyperplasia (BPH), also known as prostate hyperplasia, is one of the most common chronic diseases in the urinary system. It is listed as the two most important prostate diseases affecting middle-aged and elderly men, along with prostate cancer. Epidemiological studies have shown that when men reach the age of 40, the prostate begins to proliferate. More than 50% of men aged 60 suffer from BPH, and 90% of men in their 70s and 80s suffer from BPH. BPH can cause bladder obstruction and induce lower urinary tract symptoms (LUTS), which are often manifested as weakened urine flow, incomplete bladder emptying, frequent urination, urgency, increased nocturia, difficulty starting urination, delayed urination, painful urination, and interrupted urine flow. Although these diseases are not life-threatening, long-term distress and treatment will not only seriously reduce the quality of life and cause economic burdens, but may even cause mental illnesses such as anxiety and depression.
[0003] Currently, transurethral resection of the prostate (TURP) is the most common surgical treatment for BPH worldwide, but the surgery may cause complications such as bleeding, urethral stenosis and urinary incontinence, and has limitations for the elderly. Clinically, drugs for the treatment of BPH mainly include 5α-reductase inhibitors (finasteride, dutasteride, etc.), α1 receptor blockers (tamsulosin, terazosin), phosphodiesterase type 5 (PDE5) inhibitors and their combination. However, the potential adverse reactions behind the good drug efficacy, such as dyspnea, erectile dysfunction, low libido, ejaculation disorders, etc., bring new troubles to patients.
[0004] Active ingredients in traditional Chinese medicine are a natural treasure trove, with broad prospects for development to treat diseases. Dandelion is the dried whole herb of Taraxacum mongolicum Hand.-Mazz., Taraxacum borealisinense Kitam., or several plants of the same genus in the Asteraceae family. The 2020 edition of the Chinese Pharmacopoeia records that it can clear away heat and detoxify, reduce swelling and resolve knots, and promote diuresis and relieve stranguria. Dandelion mainly contains a variety of chemical components such as triterpenes, sesquiterpenes, flavonoids, phenolic acids, and phytosterols. Summary of the invention
[0005] In order to solve the problems existing in the prior art, the present invention screens the active ingredients of natural medicine through a large number of experiments, and provides a dandelion triterpene composition for treating prostate hyperplasia with significant efficacy and high safety.
[0006] In order to achieve the above technical objectives, the technical solution adopted by the present invention is as follows:
[0007] A dandelion triterpene composition for treating prostatic hyperplasia comprises taraxasterol, taraxasterol acetate, lupeol, taraxadone alcohol and beta-amyrin.
[0008] As a preferred embodiment, the dandelion triterpene composition for treating prostatic hyperplasia described above is characterized in that the composition is composed of taraxasterol, taraxasterol acetate, lupeol, taraxadone alcohol and β-amyrin in a weight ratio of 2-4:2-4:1.5-3:1-2:2.5-5.
[0009] As a preferred embodiment, the dandelion triterpene composition for treating prostatic hyperplasia described above is composed of taraxasterol, taraxasterol acetate, lupeol, taraxadone alcohol and β-amyrin in a weight ratio of 2:2:1.5:1:2.5.
[0010] The preparation method of the dandelion triterpene composition for treating prostatic hyperplasia described above uses the whole dandelion grass or root as raw material, extracts with ethanol, and then separates and elutes through a chromatographic column to obtain the dandelion triterpene composition.
[0011] More preferably, the preparation method of the dandelion triterpene composition for treating prostatic hyperplasia described above,
[0012] (1) taking the whole herb or root of dandelion, adding an ethanol solution with a volume concentration of 50-95% to perform ultrasonic extraction or heating reflux extraction, the extraction time is 1-2 hours, the extraction temperature is 50-90° C., the extraction times are 2-3 times, and the ethanol extract is obtained after filtering and vacuum concentration;
[0013] (2) taking the macroporous adsorption resin on the alcohol extract in step (1), and eluting with 5 to 8 column volumes of water and 40%, 60%, and 95% ethanol solutions in sequence; the macroporous adsorption resin can be selected from D101, AB-8, ADS-4, ADS-8, SPD-100, LSA-20, and XAD-5, preferably AB-8;
[0014] (3) Take the 95% ethanol elution component in step (2), remove the elution solvent, continue to add polyamide or silica gel resin, etc., undergo systematic elution and separation, and freeze-dry to obtain the monomers of each compound.
[0015] Alternatively, taraxasterol, taraxasterol acetate, lupeol, taraxadone alcohol, β-amyrin and the like can be purchased from the market.
[0016] The triterpene composition provided by the present invention is used in the preparation of a pharmaceutical product for treating prostatic hyperplasia. Preferably, the dosage form of the drug includes tablets, pills, powders, decoctions, granules, injections, capsules or decoctions.
[0017] Beneficial effects: The present invention screened out a triterpene composition for treating prostate hyperplasia through a large number of experiments. The experimental results show that the triterpene composition can improve prostate hyperplasia by inhibiting inflammatory response, improving prostate hyperplasia by regulating the androgen balance in the body, and improving prostate hyperplasia from the perspective of tissue pathological morphology, showing good efficacy in treating prostate hyperplasia. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 The results of the dandelion triterpene composition improving the tissue phenotype and prostate index of the prostate in rats with prostate hyperplasia are shown in Figure 1. A-tissue phenotype diagram, B-prostate index.
[0019] Figure 2 The results of the dandelion triterpene composition improving the tissue pathological morphology of rats with prostatic hyperplasia are shown in Figure 1. A-tissue pathological morphology, B-epithelial thickness.
[0020] Figure 3 The figure shows the effect of dandelion triterpene composition on androgen levels and inflammatory factor levels in serum and prostate tissue of rats, A-serum testosterone (T) level, B-serum prostate specific antigen (PSA) level, C-dihydrotestosterone (DHT) level in prostate tissue, D-type II 5α-reductase level in prostate tissue, E-serum tumor necrosis factor-α (TNF-α) level, F-serum interleukin-6 (IL-6) level.
[0021] Figure 4 These are the results of the dandelion triterpene composition improving collagen deposition in prostate tissue. A - Sirius red staining, B - Masson staining. DETAILED DESCRIPTION
[0022] It should be noted that the following detailed descriptions are illustrative and are intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used in the present application have the same meanings as those commonly understood by those skilled in the art to which the present application belongs.
[0023] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.
[0024] Example 1
[0025] A dandelion triterpene composition for treating prostatic hyperplasia, the composition consists of taraxasterol, taraxasterol acetate, lupeol, taraxadone alcohol and beta-amyrin alcohol in a weight ratio of 2:2:1.5:1:2.5.
[0026] Example 2
[0027] A dandelion triterpene composition for treating prostatic hyperplasia, the composition consists of taraxasterol, taraxasterol acetate, lupeol, taraxadone alcohol and beta-amyrin alcohol in a weight ratio of 3:3:2.5:1.5:4.
[0028] Example 3 Therapeutic effect of triterpene composition on testosterone propionate-induced prostatic hyperplasia in rats
[0029] 1. Experimental Materials
[0030] Testosterone propionate (batch number GC39451) was purchased from Glpbio; corn oil (batch number M13IS209356) was purchased from Shanghai Yuanye Biotechnology Co., Ltd.; taraxasterol, taraxasterol acetate, lupeol, taraxadone, β-amyrin and sodium carboxymethylcellulose were purchased from Shanghai Yuanye Biotechnology Co., Ltd.; finasteride (batch number W021658) was purchased from Hangzhou Merck Pharmaceutical Co., Ltd.; Prolean tablets were purchased from Zhejiang Kangenbei Pharmaceutical Co., Ltd.; SPF-grade male SD rats, 6-8 weeks old, were purchased from Shanghai Slake Experimental Animal Co., Ltd.
[0031] 2. Establishment of prostate hyperplasia rat model and drug treatment
[0032] Male SD rats were divided into 6 groups, 8 in each group. Testosterone propionate dissolved in corn oil was subcutaneously injected at 5 mg / kg / d for 4 consecutive weeks to induce a prostate hyperplasia model in rats, and the control group was subcutaneously injected with an equal amount of corn oil. The control group and the model group were intragastrically administered with 0.5% sodium carboxymethyl cellulose, the finasteride group was administered with 1 mg / kg / d finasteride, and the low-dose and high-dose groups of the dandelion triterpene composition of Example 1 were administered with 10 mg / kg / d and 20 mg / kg / d, respectively, for 4 consecutive weeks.
[0033] 3. Sampling and Pharmacodynamic Evaluation
[0034] 24 hours after the last administration, the rats were anesthetized, blood was collected from the abdominal aorta, and the rats were killed. The prostate was dissected and the prostate index was calculated (prostate index (mg / g) = total wet weight of prostate tissue / rat body weight); another part of the prostate was fixed in 4% paraformaldehyde fixative for histopathological sectioning and staining; ELISA kits were used to detect the levels of serum testosterone (T), prostate specific antigen (PSA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in each group, and the levels of dihydrotestosterone (DHT) and type II 5α-reductase (5α-reductase 2) in prostate tissue were detected.
[0035] 4. Experimental Results
[0036] like Figure 1 As shown, compared with the control group, the prostate of the model group rats was enlarged and the prostate index was significantly increased (P<0.01); compared with the model group, the prostate of the positive drug finasteride group and the low-dose group and high-dose group of the dandelion triterpene composition was reduced to different degrees, and the prostate index was significantly reduced (P<0.05 or P<0.01). The results show that the dandelion triterpene composition can treat prostate hyperplasia.
[0037] The histopathological morphology of each group was Figure 2 As shown, the prostate epithelial cells in the blank group were arranged in a normal, orderly single layer, while the epithelial tissue in the model group was folded and stacked with a large number of papillary protrusions, and the glandular cavity area was greatly reduced. Both the low-dose and high-dose groups of the dandelion triterpene composition were alleviated; in addition, the statistical results of epithelial thickness showed that the low-dose and high-dose groups of the dandelion triterpene composition could significantly reduce the thickness of the hyperplastic epithelium (P<0.01), indicating that the dandelion triterpene composition can improve prostate hyperplasia from the perspective of tissue pathology.
[0038] The levels of T, PSA, DHT and 5α-reductase in rat serum or prostate tissue were determined according to the instructions of the ELISA kit. Figure 4 As shown in A and B, compared with the blank group, the levels of T and PSA in serum were increased, and the levels of DHT and 5α-reductase in prostate tissue were increased, while they were significantly decreased after treatment with the dandelion triterpene composition (P<0.01), indicating that the dandelion triterpene composition can improve prostate hyperplasia by regulating the balance of androgens in the body.
[0039] The results of the detection of inflammatory factors TNF-α and IL-6 levels in the serum of rats in each group are shown in Figure 3As shown in DE, the level of inflammatory factors in the model group was significantly higher than that in the control group (P<0.01), and both the low-dose and high-dose groups of the dandelion triterpene composition could significantly reduce the level of inflammatory factors (P<0.01), indicating that the dandelion triterpene composition can improve prostate hyperplasia by inhibiting inflammatory response.
[0040] Sirius red staining and Masson staining were used to observe collagen deposition in the prostate tissues of each group. Figure 4 As shown, Sirius red and Masson staining showed that there was obvious collagen deposition in the model group of prostate hyperplasia rats; compared with the model group, both the low-dose and high-dose groups of the dandelion triterpene composition effectively inhibited the collagen deposition in the rat prostate, indicating that the dandelion triterpene composition has the potential to improve prostate fibrosis.
[0041] The above examples are only used to illustrate the technical solution of the present invention and are not intended to limit it. Although the present invention is described in detail with reference to the given examples, a person of ordinary skill in the art may modify or replace the technical solution of the present invention as required without departing from the spirit and scope of the technical solution of the present invention.
Claims
1. A dandelion triterpene composition for treating prostatic hyperplasia, characterized in that: The composition includes taraxasterol, taraxasterol acetate, lupeol, taraxerol and beta-amyrin.
2. The dandelion triterpene composition for treating prostatic hyperplasia according to claim 1, characterized in that: The composition consists of taraxasterol, taraxasterol acetate, lupeol, taraxacol and beta-amyrin alcohol in a weight ratio of 2-4:2-4:1.5-3:1-2:2.5-5.
3. The dandelion triterpene composition for treating prostatic hyperplasia according to claim 1, characterized in that: The composition consists of taraxasterol, taraxasterol acetate, lupeol, taraxadone alcohol and beta-amyrin alcohol in a weight ratio of 2:2:1.5:1:2.
5.
4. The method for preparing the dandelion triterpene composition for treating prostatic hyperplasia according to any one of claims 1 to 3, characterized in that: The whole dandelion grass or root is used as raw material, extracted with ethanol, and then eluted and separated through a chromatographic column to obtain the product.
5. Use of the composition according to any one of claims 1 to 3 in the preparation of a pharmaceutical product for treating prostatic hyperplasia.
6. The use according to claim 5, characterized in that: The composition and the pharmaceutically acceptable carrier are made into tablets, pills, powders, decoctions, granules, injections, mixtures, capsules or decoctions.