Composition, preparation, preparation method and application for treating benign prostatic hyperplasia

Abstract

The present invention discloses a composition, a preparation and a preparation method and application thereof for treating benign prostatic hyperplasia, relating to the technical field of traditional Chinese medicine. The composition comprises the following components: Flemingia philippinensis Merr. ex Rolfe, Curcuma zedoaria (Christm.) Rosc., Eucommia ulmoides Oliv., Achyranthes bidentata Blume, Codonopsis pilosula (Franch.) Nannf., Astragalus membranaceus (Fisch.) Bunge, Cinnamomum cassia Presl, Curculigo orchioides Gaertn., Epimedium brevicornu Maxim., Phellodendron amurense Rupr., Poria cocos (Schw.) Wolf, Paeonia suffruticosa Andr., Paeonia lactiflora Pall. and Prunus persica (L.) Batsch. The preparation is prepared from the composition as a traditional Chinese medicine raw material medicine, and the preparation method comprises: mixing the raw material medicines, soaking in water, decocting and taking the medicinal liquid, and further processing the obtained medicinal liquid into a common traditional Chinese medicine preparation according to a conventional process. In the treatment process of benign prostatic hyperplasia with the traditional Chinese medicine composition and the preparation thereof, patients rarely have situations such as orthostatic hypotension and erectile dysfunction, and are superior to the treatment with pure western medicine in relieving the prostate symptoms of patients, improving the quality of life and improving the lower urinary tract symptoms, and moreover, the effects of relieving the symptoms of soreness and weakness of the waist and knees, fatigue and weakness, and aversion to cold and cold limbs are obvious.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating benign prostatic hyperplasia, a preparation made from the traditional Chinese medicine composition, a preparation method of the preparation, and the application of the traditional Chinese medicine composition or the preparation. Background Art

[0002] Benign prostatic hyperplasia (BPH) is a common diagnosis of progressive enlargement of the prostate in elderly men, and the prevalence increases with population aging. Among Asian men, the prevalence of BPH is as high as 62.8% after the age of 40, seriously affecting the quality of life of patients. The research on the diagnosis and treatment of BPH has become a hot topic and focus of national concern.

[0003] The pathogenesis and disease progression mechanism of BPH are not yet clear. The first-line treatment of BPH is the use of α-blockers alone or in combination with 5α-reductase inhibitors, although they show different therapeutic effects on symptoms and disease progression. However, in clinical treatment, many adverse reactions have been observed in patients, including dizziness, ejaculation dysfunction, orthostatic hypotension, retrograde ejaculation, etc. Over time, many patients either have no response to the current treatment methods or develop drug resistance to the current medical methods. Long-term medication not only fails to cure the disease but also causes many side effects, and the disease still progresses continuously, so surgical intervention has to be adopted. Surgical treatment also has many complications, such as bleeding, urinary incontinence, transurethral resection syndrome, retrograde ejaculation, and even erectile dysfunction, and there is a recurrence after surgery. Modern medicine has a good helping effect on relieving the dysuria of patients in the treatment of BPH, but it is still unsatisfactory in improving the symptoms of kidney qi deficiency, soreness and weakness of the waist and knees, dizziness and tinnitus, etc. accompanied by the attenuation of tiankui in elderly men, and it cannot solve the troubles brought by these problems. Therefore, there is an urgent clinical need for a BPH alternative therapy with definite curative effect and few side effects, and herbs with milder efficacy are considered as complementary and alternative treatment methods for BPH.

[0004] Traditional Chinese medicine has been widely used in relieving the clinical discomfort of BPH and has good efficacy. More and more patients choose to use traditional Chinese medicine to prevent and treat BPH. As an important branch of traditional Chinese medicine, Zhuang medicine has accumulated rich knowledge and experience in disease prevention, diagnosis, medical treatment and drug application in long-term medical practice, and has formed a systematic Zhuang medicine theory, including the natural view and holistic view of "yin and yang as the basis" and the synchronization of the three qi of "heaven, earth and man", the Zhuang medicine physiological and pathological view of the three roads and two paths of "qi channel", "valley channel", "water channel", "dragon road" and "fire road", and the Zhuang medicine etiology and pathogenesis theory of "toxic deficiency leads to all kinds of diseases", and the treatment principle of "regulating qi, detoxifying and replenishing deficiency". Zhuang medicine has various methods of treating diseases, which can be roughly divided into internal treatment and external treatment, such as Zhuang medicine acupuncture, Zhuang medicine moxibustion, Zhuang medicine scraping, drug fumigation and fumigation therapy, wearing medicine therapy, plaster therapy, drug bamboo cup therapy, rolling egg therapy, etc. Each major treatment method contains a variety of specific treatment methods, which are widely used in clinical practice, with definite efficacy and few side effects.

[0005] At present, there are few public literatures on the application of Zhuang medicine theories to the in-depth research and development of drugs for the treatment of benign prostatic hyperplasia. There are also no mature Zhuang medicine products with few side effects and good clinical effects on the market. These products can play an effective supplementary or alternative treatment role in addressing the many side effects, adverse reactions, drug resistance problems caused by long-term use of Western medicines in the treatment of benign prostatic hyperplasia, as well as the difficulty in improving patients' quality of life. Summary of the invention

[0006] The first object of the present application is to provide a composition for treating benign prostatic hyperplasia. To this end, the present application adopts the following technical solutions:

[0007] A composition for treating benign prostatic hyperplasia comprises the following components in parts by weight: 15-20 parts of Radix Glehniae, 6-9 parts of Rhizoma Curcumae, 12-15 parts of Eucommia ulmoides, 9-12 parts of Radix Achyranthis Bidentatae, 12-15 parts of Codonopsis pilosulae, 15-20 parts of Radix Astragali, 6-9 parts of Cortex Cinnamomi, 10-12 parts of Curculigo orchioides, 10-12 parts of Epimedium, 12-15 parts of Cortex Phellodendri, 10-15 parts of Poria, 10-12 parts of Cortex Moutan, 10-15 parts of Radix Paeoniae Rubra and 10-15 parts of Semen Persicae.

[0008] In at least one embodiment, the composition comprises the following components, in parts by weight: 15 parts of Rhizoma Curculigoe, 6 parts of Rhizoma Curcumae, 15 parts of Eucommia ulmoides, 9 parts of Rhizoma Achyranthis Bidentatae, 12 parts of Codonopsis pilosula, 15 parts of Radix Astragali, 6 parts of Cinnamon Bark, 10 parts of Curculigo orchioides, 10 parts of Epimedium, 12 parts of Phellodendron amurense, 10 parts of Poria, 10 parts of Paeonia suffruticosa, 10 parts of Paeonia lactiflora and 10 parts of Semen Persicae.

[0009] The above components are conventional Chinese medicine raw materials in the art, and their common sources are as follows: Flemingia philippinensis Merr. ex Rolfe, the root of Flemingia philippinensis Merr. ex Rolfe of the Leguminosae family; Curcuma zedoaria (Christm.) Rosc., the dried rhizome of Curcuma phaeocaulis Valeton, Curcuma kwangsiensis S. G. Lee et C. F. Liang or Curcuma wenyujin Y. H. Chen et C. Ling of the Zingiberaceae family. In this application, Curcuma kwangsiensis S. G. Lee et C. F. Liang is preferred; Eucommia ulmoides Oliv., the dried bark of Eucommia ulmoides Oliv. of the Eucommiaceae family; Achyranthes bidentata Blume, the dried root of Achyranthes bidentata Blume of the Amaranthaceae family; Codonopsis pilosula (Franch.) Nannf., the dried root of Codonopsis pilosula (Franch.) Nannf., Codonopsis pilosula Nannf. var. modesta (Nannf.) L. T. Shen or Codonopsis tangshen Oliv. of the Campanulaceae family; Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) Hsiao or Astragalus membranaceus (Fisch.) Bunge, the dried root of Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) Hsiao or Astragalus membranaceus (Fisch.) Bunge of the Leguminosae family; Cinnamomum cassia Presl, the dried bark of Cinnamomum cassia Presl of the Lauraceae family. Curculigo orchioides Gaertn., the rhizome of Curculigo orchioides Gaertn. of the Amaryllidaceae family. Epimedium brevicornu Maxim., also known as Epimedium sagittatum (Sieb. et Zucc.) Maxim., Herba Epimedii, Lotus corniculatus L., Trifurcate Wind, Goat Horn Wind, and Triangular Lotus, is the dried above-ground part of Epimedium brevicornu Maxim., Epimedium sagittatum (Sieb. et Zucc.) Maxim., Epimedium pubescens Maxim., Epimedium wushanense T. S. Ying or Epimedium koreanum Nakai of the Berberidaceae family. Phellodendron amurense Rupr. or Phellodendron chinense Schneid., the dried bark of Phellodendron amurense Rupr. or Phellodendron chinense Schneid. of the Rutaceae family. Poria cocos (Schw.) Wolf, the dried sclerotium of Poria cocos (Schw.) Wolf of the Polyporaceae family. Cortex Moutan, the dried root bark of Paeonia suffruticosa Andr. of the Ranunculaceae family. Radix Paeoniae Rubra, the dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch of the Ranunculaceae family. Semen Persicae, the dried ripe seed of Prunus persica (L.) Batsch or Prunus davidiana (Carr.) Franch. of the Rosaceae family.

[0010] The second object of this application is to provide a preparation for treating benign prostatic hyperplasia. For this purpose, the following technical solutions are also adopted in this application:

[0011] A preparation for treating benign prostatic hyperplasia is prepared from the components of the above composition as raw materials according to conventional processes into common traditional Chinese medicine preparations.

[0012] In at least one embodiment, the traditional Chinese medicine preparation includes liquid preparations, semi-solid preparations or solid preparations.

[0013] In at least one embodiment, the dosage form of the traditional Chinese medicine preparation includes decoctions, extract pastes, pills, tablets, granules or capsules.

[0014] The preparation of this application is prepared from the above-mentioned traditional Chinese medicine composition as the raw material, and can exist in the form of solid, semi-solid or liquid pharmaceutical preparations, for example. These forms of pharmaceutical preparations contain the traditional Chinese medicine composition or its extract of this application as the active ingredient, and can also be mixed with organic or inorganic excipients and adjuvants, and are suitable for external, enteral and parenteral use. Possibly, the active ingredient can be compounded with commonly used non-toxic pharmaceutical excipients to make extract pastes, pills, tablets, pills, capsules, solutions, emulsions, suspensions and any dosage forms that can be used. The excipients or adjuvants of this application include talc, water, glucose, honey, lactose, gum arabic, gelatin, mannitol, starch, magnesium trisilicate, keratin, colloidal silicon and any carrier that can prepare solid, semi-solid or liquid preparations. In addition, auxiliary, stabilizing, thickening, coloring, flavoring and other adjuvants can also be used.

[0015] The third object of the present application is to provide a preparation method of the above-mentioned preparation. For this purpose, the present application also adopts the following technical solutions:

[0016] A preparation method of the above-mentioned preparation, comprising: mixing the above-mentioned raw medicinal materials, soaking them in water, then decocting, taking the medicinal liquid after decocting, and the obtained medicinal liquid can be used as a decoction, or the obtained medicinal liquid is further processed into other traditional Chinese medicine preparations according to conventional processes.

[0017] In at least one embodiment, when soaking in water, the added water is 5-15 times the total weight of the raw medicinal materials.

[0018] In at least one embodiment, when soaking in water, the soaking time is 20-60 minutes.

[0019] In at least one embodiment, the number of decocting times is 1-3 times, 1-2 hours each time, and the filtrates are combined after filtration to obtain the medicinal liquid.

[0020] The fourth object of the present application is to provide the use of the above-mentioned composition or the above-mentioned preparation in the preparation of a drug for treating benign prostatic hyperplasia. Among them, the composition is the traditional Chinese medicine composition provided by the first object of the present application; the preparation is the preparation provided by the second object of the present application, or the preparation prepared by the preparation method provided by the third object of the present application.

[0021] Compared with the prior art, the present application at least achieves the following beneficial effects: The traditional Chinese medicine composition and preparation of the present application, based on the treatment principles of Zhuang medicine of "regulating qi, detoxifying, and tonifying deficiency", start from regulating the "qi tract", "water tract", and "fire tract", tonify the kidney qi, and regulate and dredge the lower jiao, and achieve good curative effects in the clinical treatment of BPH. It can play a certain role in balancing and solving the problems of more side effects, adverse reactions, drug resistance during long-term medication, and difficulty in better improving the quality of life of patients when treating benign prostatic hyperplasia with western medicine, and provides a feasible supplementary or alternative treatment plan for the conventional western medicine therapy. Description of the Drawings

[0022] Figure 1 It is a compound-target diagram in the network pharmacology prediction experiment;

[0023] Figure 2 It is a protein interaction diagram in the network pharmacology prediction experiment;

[0024] Figure 3 It is a GO analysis diagram in the network pharmacology prediction experiment;

[0025] Figure 4 It is a KEGG pathway diagram in the network pharmacology prediction experiment;

[0026] Figure 5 It is a HE staining diagram of the blank group in the animal experiment;

[0027] Figure 6 It is the HE staining diagram of the model group in animal experiments;

[0028] Figure 7 It is the HE staining diagram of the Qianlong Shutong Prescription group in animal experiments;

[0029] Figure 8 It is the comparison diagram of traditional Chinese medicine syndrome scores in clinical trials;

[0030] Figure 9 It is the comparison diagram of quality of life scores in clinical trials. Specific implementation manners

[0031] The present application will be described in detail below with reference to the exemplary embodiments in the drawings. It should be understood, however, that the present application can be implemented in many different forms and should not be construed as limited to the embodiments set forth herein. These embodiments are provided herein to make the disclosure of the present application more complete and to fully convey the concept of the present application to those skilled in the art.

[0032] On the one hand, the present application provides a composition for treating benign prostatic hyperplasia (hereinafter referred to as: Qianlong Shutong Prescription), which, by weight, comprises the following components: 15-20 parts of Flemingia philippinensis, 6-9 parts of Curcuma phaeocaulis, 12-15 parts of Eucommia ulmoides, 9-12 parts of Achyranthes bidentata, 12-15 parts of Codonopsis pilosula, 15-20 parts of Astragalus membranaceus, 6-9 parts of Cinnamomum cassia, 10-12 parts of Curculigo orchioides, 10-12 parts of Epimedium brevicornu, 12-15 parts of Phellodendron amurense, 10-15 parts of Poria cocos, 10-12 parts of Paeonia suffruticosa, 10-15 parts of Paeonia lactiflora, and 10-15 parts of Prunus persica.

[0033] The traditional Chinese medicine composition of the present application adopts the form of a Zhuang medicine compound prescription. Among the components of the above composition, Curcuma phaeocaulis is preferably Curcuma kwangsiensis. In the prescription, Curcuma kwangsiensis, Cinnamomum cassia, etc. are all included in the "Ten Flavors of Guangxi" of Guangxi genuine medicinal materials [Cinnamomum cassia (including Ramulus Cinnamomi), Siraitia grosvenorii, Illicium verum, Curcuma kwangsiensis (including C. kwangsiensis), Dimocarpus longan, Sophora tonkinensis, Millettia reticulata, Abrus cantoniensis, Zanthoxylum nitidum, Pheretima guangxiensis], which conforms to the medication experience of Zhuang medicine and the geographical and climatic environment of Guangxi.

[0034] The above composition is most commonly made into a decoction. When using the medicine, the dosage of the medicine in the prescription can be flexibly adjusted according to the individual situation of the patient. Herein, the inventor also provides a most commonly used preferred ratio. That is, the composition for treating benign prostatic hyperplasia (Qianlong Shutong Prescription), by weight, comprises the following components: 15 parts of Flemingia philippinensis, 6 parts of Curcuma kwangsiensis, 15 parts of Eucommia ulmoides, 9 parts of Achyranthes bidentata, 12 parts of Codonopsis pilosula, 15 parts of Astragalus membranaceus, 6 parts of Cinnamomum cassia, 10 parts of Curculigo orchioides, 10 parts of Epimedium brevicornu, 12 parts of Phellodendron amurense, 10 parts of Poria cocos, 10 parts of Paeonia suffruticosa, 10 parts of Paeonia lactiflora, and 10 parts of Prunus persica.

[0035] Using the above composition as the raw material drug, it can not only be made into a decoction, but also be made into other common traditional Chinese medicine preparations according to conventional processes. The traditional Chinese medicine preparations include liquid preparations, semi-solid preparations or solid preparations. Further, the dosage forms of the traditional Chinese medicine preparations may also include extract pastes, pills, tablets, granules, capsules, etc., but are not limited to the above dosage forms. Any traditional Chinese medicine preparation containing the above composition or using the extract of the composition as the active ingredient can be considered to be within the protection scope of this application.

[0036] On the other hand, this application also provides a preparation method of the above preparation, including: mixing the above raw material drug, soaking it in water, then decocting, taking the medicinal liquid after decocting, and the obtained medicinal liquid can be used as a decoction, or the obtained medicinal liquid can be further processed into other traditional Chinese medicine preparations according to conventional processes. The conventional processes may include concentration, drying, mixing, granulation, tabletting, disinfection, packaging and other common pharmaceutical processes in the art.

[0037] Optionally, when soaking in water, the added water is 5-15 times the total weight of the raw material drug, and the soaking time is 20-60 minutes.

[0038] Optionally, the number of decocting times is 1-3 times, 1-2 hours each time, and the filtrates are combined after filtration to obtain the medicinal liquid.

[0039] Zhuang medicine believes that the channel through which the qi of the human body exchanges with the qi of nature is called the qi channel. The qi flowing in the qi channel contains both the congenital qi before a person is born and the fresh qi inhaled from nature after birth, as well as the qi distributed in each zang-fu organ generated by the interaction of congenital qi and natural qi. It is the direct driving force for promoting the zang-fu organs to perform their respective functions; water is the source of life. The human body takes in and discharges water through the water channel, and the channel for discharging sweat and urine in the human body is called the water channel. The core of the "three channels and two paths" theory of Zhuang medicine is the word "unobstructed", which coincides with the treatment principle of BPH. Clinical research has found that Zhuang medicine has few side effects in the treatment of BPH and has the advantages of safety, effectiveness and low cost. According to the treatment principles of Zhuang medicine of "regulating qi, detoxifying and tonifying deficiency", the inventor starts from regulating the "qi channel", "water channel" and "fire path", tonifying the kidney qi, dredging and regulating the lower energizer, and uses the aforementioned Qianlong Shutong Prescription for clinical treatment of BPH, and can achieve good results.

[0040] In the formulation of the traditional Chinese medicine composition of the present invention, the monarch drug is Flemingia philippinensis, which is sweet, slightly astringent, and neutral in nature, tonifying the liver and kidney, dispelling wind-dampness, and strengthening the waist and knees. Eucommia ulmoides is sweet and slightly pungent, warm in nature, and belongs to the liver and kidney meridians, with the functions of tonifying the liver and kidney and strengthening the bones and muscles; Codonopsis pilosula is sweet and neutral, belonging to the spleen and lung meridians, replenishing middle qi, promoting the production of body fluid and nourishing blood, to assist the monarch drug. Astragalus membranaceus is sweet in taste and warm in nature, entering the spleen and lung meridians, being the key drug for replenishing qi, having the functions of replenishing middle qi, ascending the clear and descending the turbid, and can promote blood circulation, to dissipate blood stasis, boost qi and raise yang, and promote diuresis and alleviate edema; the ministerial drugs are Epimedium brevicornu, Cinnamomum cassia, and Curculigo orchioides for tonifying the kidney yang; Epimedium brevicornu is pungent, sweet, and warm. Entering the liver and kidney meridians, warming the kidney and assisting yang, dispelling wind-dampness. Curculigo orchioides is pungent, hot, and belongs to the kidney meridian, warming the kidney and strengthening yang, dispelling cold and dampness. Cinnamomum cassia is a substance with thick taste, sweet, pungent, and extremely hot, going downward and walking inside, having the function of warming and transporting yang qi, being able to warm and tonify the fire of the gate of vitality, and being combined with Phellodendron amurense to achieve the effect of coordinating water and fire and balancing yin and yang. The adjuvant drug for restraining is Phellodendron amurense, which is bitter in taste and cold in nature, entering the kidney and bladder meridians, and can strengthen the kidney yin and promote diuresis and remove dampness; the adjuvant drugs are Paeonia suffruticosa, Paeonia lactiflora, Prunus persica, and Curcuma kwangsiensis for promoting qi and activating blood circulation, and Poria cocos and Atractylodes macrocephala for strengthening the spleen and promoting diuresis; the guiding drug is Achyranthes bidentata for promoting blood circulation and benefiting the kidney, guiding the drug directly to the lesion site. For those with blood stasis and dysuria, Achyranthes bidentata can disperse blood stasis, strengthen the feet and knees, and guide the drug downward. The combination of all the drugs has the effects of tonifying the kidney and replenishing qi, promoting blood circulation and removing stasis, and promoting diuresis and expelling turbidity.

[0041] The efficacy of the above composition and preparation: It has the effects of tonifying the kidney and replenishing qi, promoting blood circulation and removing stasis, and promoting diuresis and expelling turbidity. Indications: Benign prostatic hyperplasia patients with frequent urination, especially severe at night, thin urine stream, incomplete urinary dribbling, short urinary course, or incomplete urination, or even anuria: listlessness, sallow complexion, fear of cold and cold limbs; pale and moist tongue, thin and white coating, deep and thready pulse. Therefore, the present application also provides the use of the above composition and preparation in the preparation of drugs for treating benign prostatic hyperplasia.

[0042] In addition, the present application also provides multiple specific examples to further elaborate on the raw material composition and preparation method of the traditional Chinese medicine preparation for treating benign prostatic hyperplasia, specifically as follows:

[0043] Example 1

[0044] 1) Weigh the raw materials according to the following parts by weight: 15 parts of Flemingia philippinensis, 6 parts of Curcuma kwangsiensis, 15 parts of Eucommia ulmoides, 9 parts of Achyranthes bidentata, 12 parts of Codonopsis pilosula, 15 parts of Astragalus membranaceus, 6 parts of Cinnamomum cassia, 10 parts of Curculigo orchioides, 10 parts of Epimedium brevicornu, 12 parts of Phellodendron amurense, 10 parts of Poria cocos, 10 parts of Paeonia suffruticosa, 10 parts of Paeonia lactiflora, and 10 parts of Prunus persica.

[0045] 2) Mix the above raw materials, add 10 times the total weight of the raw materials of water, soak for 30 minutes, then decoct 2 times, each time for 1.5 hours, filter and combine the filtrates, and the obtained medicinal liquid is used as a decoction.

[0046] Example 2

[0047] 1) Weigh the raw medicinal materials according to the following parts by weight: 15 parts of Flemingia philippinensis Merr. ex Rolfe, 8 parts of Curcuma kwangsiensis S. G. Lee et C. F. Liang, 15 parts of Eucommia ulmoides Oliv., 9 parts of Achyranthes bidentata Blume, 13 parts of Codonopsis pilosula (Franch.) Nannf., 20 parts of Astragalus membranaceus (Fisch.) Bunge, 6 parts of Cinnamomum cassia Presl, 11 parts of Curculigo orchioides Gaertn., 12 parts of Epimedium brevicornu Maxim., 12 parts of Phellodendron amurense Rupr., 13 parts of Poria cocos (Schw.) Wolf, 12 parts of Paeonia suffruticosa Andr., 10 parts of Paeonia lactiflora Pall., and 12 parts of Prunus persica (L.) Batsch.

[0048] 2) Mix the above raw medicinal materials, add water 5 times the total weight of the raw medicinal materials, soak for 40 minutes, then decoct 3 times, each time for 1 hour. After filtration, combine the filtrates. Concentrate the obtained medicinal liquid into an extract, add refined honey to make a paste, and prepare a decoction extract.

[0049] Example 3

[0050] 1) Weigh the raw medicinal materials according to the following parts by weight: 18 parts of Flemingia philippinensis Merr. ex Rolfe, 9 parts of Curcuma kwangsiensis S. G. Lee et C. F. Liang, 12 parts of Eucommia ulmoides Oliv., 10 parts of Achyranthes bidentata Blume, 15 parts of Codonopsis pilosula (Franch.) Nannf., 15 parts of Astragalus membranaceus (Fisch.) Bunge, 8 parts of Cinnamomum cassia Presl, 12 parts of Curculigo orchioides Gaertn., 10 parts of Epimedium brevicornu Maxim., 13 parts of Phellodendron amurense Rupr., 15 parts of Poria cocos (Schw.) Wolf, 10 parts of Paeonia suffruticosa Andr., 12 parts of Paeonia lactiflora Pall., and 15 parts of Prunus persica (L.) Batsch.

[0051] 2) Mix the above raw medicinal materials, add water 12 times the total weight of the raw medicinal materials, soak for 60 minutes, then decoct 1 time, each time for 1.5 hours. After filtration, combine the filtrates. Concentrate, dry, and pulverize the obtained medicinal liquid to make fine powder. Add auxiliary materials and press into tablets to prepare tablets.

[0052] Example 4

[0053] 1) Weigh the raw medicinal materials according to the following parts by weight: 20 parts of Flemingia philippinensis Merr. ex Rolfe, 6 parts of Curcuma kwangsiensis S. G. Lee et C. F. Liang, 13 parts of Eucommia ulmoides Oliv., 12 parts of Achyranthes bidentata Blume, 12 parts of Codonopsis pilosula (Franch.) Nannf., 18 parts of Astragalus membranaceus (Fisch.) Bunge, 9 parts of Cinnamomum cassia Presl, 10 parts of Curculigo orchioides Gaertn., 11 parts of Epimedium brevicornu Maxim., 15 parts of Phellodendron amurense Rupr., 10 parts of Poria cocos (Schw.) Wolf, 11 parts of Paeonia suffruticosa Andr., 15 parts of Paeonia lactiflora Pall., and 10 parts of Prunus persica (L.) Batsch.

[0054] 2) Mix the above raw medicinal materials, add water 15 times the total weight of the raw medicinal materials, soak for 20 minutes, then decoct 2 times, each time for 2 hours. After filtration, combine the filtrates. Concentrate, dry, and pulverize the obtained medicinal liquid to make fine powder. Add auxiliary materials and granulate, then pack with capsules to prepare capsule preparations.

[0055] To illustrate and verify the efficacy of the composition and preparation of the present application, the present application also provides the following test examples:

[0056] Test Example 1: Network Pharmacology Prediction

[0057] 1) Collection of Compounds

[0058] All compounds of Qianlong Shutong Prescription were retrieved using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform (http: / / ibts.hkbu.edu.hk / LSP / tcmsp.php), and the active compounds were obtained as the premise for activity research.

[0059] 2) Construction of compound-target network and analysis of topological properties

[0060] The active compounds and targets of Qianlong Shutong Prescription were used to construct a compound-target network by Cytoscape 3.4.0 software (http: / / www.cytoscape.org / ). Nodes with higher degree centrality (DC) and corresponding closeness centrality (CC) were selected for topological analysis to identify key compounds or targets. The results are as Figure 1 shown.

[0061] 3) Obtaining intersection targets and combination

[0062] Disease targets from GeneCards, OMIM, and CTD databases were used, and Venny 2.1.0 software (http: / / bioinfogp.cnb.csic.es / tools / venny / index.html) was applied to construct the intersection targets of traditional Chinese medicine active ingredients and diseases, so as to explore the targeting effect of the active ingredients of Qianlong Shutong Prescription on BPH targets.

[0063] 4) Construction of the target protein-protein interaction (PPI) network of Qianlong Shutong Prescription

[0064] The String 10.0 software (http: / / string-db.org) was used to analyze the intersection target genes, and data with a confidence level higher than 0.9 were screened. Cytoscape was used to process the text data, and the node size and color were adjusted to construct a complete target PPI network, so as to identify the key regulatory proteins acting in the network. The results are as Figure 2 shown.

[0065] 5) Gene ontology (GO) function and KEGG pathway enrichment analysis

[0066] The GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersection targets were performed using the David v6.7 database (https: / / david.ncifcrf.gov / ). The top 30 related signaling pathways were screened from the KEGG pathway enrichment analysis through the Omicshare cloud platform (http: / / www.omicshare.com / ) to form a bubble plot, so as to clarify the biological functions of the chemical components of the drug on BPH targets and their regulatory roles in related signaling pathways. The obtained results are as Figure 3 and Figure 4 shown.

[0067] The results showed that through the analysis of 14 herbs in Qianlong Shutong Prescription, 248 active ingredients of the drug were obtained, including flemiphilippinin C, hederagenin, wenjine, bisdemethoxycurcumin, Dehydrodieugenol, etc., among which there were a large number of components that could delay or inhibit the development process of benign prostatic hyperplasia. After screening, 287 targets with a relatively high degree of relevance to BPH were obtained, including CHRM1, GABRA2, GABRA3, GABRA1, GRIA2, etc. Further through GO analysis and KEGG analysis, it was clarified that the signaling pathways involved in the treatment of BPH by Qianlong Shutong Prescription included 182 pathways such as PI3K-Akt. Qianlong Shutong Prescription may play a role in the treatment of benign prostatic hyperplasia through pathways such as PI3K-Akt and MAPK, and through biological processes such as oxidative stress response, regulation of apoptosis signaling pathway, and reactive oxygen metabolism.

[0068] Experimental Example 2: Animal Experiment

[0069] 1) BPH rat model establishment and grouping

[0070] A total of 9 SPF-grade male SD rats aged 12 weeks and weighing 200 - 300 g were used.

[0071] Model establishment method: After surgical castration, inject testosterone propionate injection subcutaneously at a dose of 5 mg / kg once a day for 4 consecutive weeks. The blank control group was injected with an equal amount of solvent. They were randomly divided into a blank group, a model group, and a Qianlong Shutong Prescription group.

[0072] 2) Drug intervention research and detection

[0073] Using BPH model rats as the research object, Qianlong Shutong Prescription was used for intervention for 4 weeks. The dosage was calculated according to the dose conversion formula for humans and animals in "Laboratory Animal Science" (edited by He Cheng, China Agricultural University Press, February 2013). The human dosage of the drug was: 1 dose at a time, 2 times a day, and each dose was 150 g / 60 kg = 2.5 g / kg / d; the dosage of the drug for rats: according to the conversion coefficient of human / rat body surface area of 6.3, the dosage was calculated as 2.5 g / kg / d * 6.3 = 15.75 g / kg / d.

[0074] 3) Specimen collection

[0075] 24 hours after the last administration, the body weight of the rats was measured, and the prostate of the rats was quickly removed after anesthesia and sacrifice.

[0076] 4) Index detection

[0077] HE pathological staining was used to observe the prostate structure under a light microscope, and the results were as Figures 5 - 7 shown.

[0078] The results showed that the prostate epithelium, glandular lumen and stroma of the rats in the blank group were normal; the prostate epithelium of the rats in the model group was significantly hyperplastic, protruding into the lumen in a papillary shape, the number of glands increased, the glandular lumen was significantly deformed, and the connective tissue was significantly hyperplastic; the prostate epithelium, glandular lumen and stroma of the glands in the Qianlong Shutong Prescription group were basically restored to normal, and a very small part protruded into the lumen in a papillary shape. It shows that the traditional Chinese medicine composition and its preparation of the present application can improve benign prostatic hyperplasia.

[0079] Test example 3: Clinical trial

[0080] 1. Source of cases

[0081] 160 BPH patients with kidney yang deficiency syndrome who visited Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from July 2021 to March 2023 were divided into an observation group and a control group by the random number table method, with 80 cases in each group. This study has obtained the review and approval of the Ethics Committee of Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine.

[0082] 2. Diagnostic criteria

[0083] 2.1 Western medicine diagnostic criteria

[0084] Western medicine diagnostic criteria: Refer to the "Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment Guidelines for Benign Prostatic Hyperplasia". ① Men over 50 years old have lower urinary tract symptoms; ② Digital rectal examination: an enlarged gland is felt; ③ B-ultrasound: the prostate volume is enlarged; ④ B-ultrasound: there is residual urine in the bladder; ⑤ Maximum urinary flow rate measurement: when the urine volume is greater than 150 ml, Qmax is less than 15 ml / s. The diagnosis can be made if ①②③ are met, with or without ④ and ⑤.

[0085] 2.2 Traditional Chinese medicine diagnostic criteria

[0086] Refer to the diagnostic criteria of "Jinglong" in "External Medicine of Traditional Chinese Medicine" (the tenth edition of the national planning textbook for higher Chinese medicine institutions), and the syndrome differentiation is deficiency of kidney yang syndrome, that is, manifested as frequent urination, especially severe at night, thin urine stream, incomplete dripping, short urine course, or dribbling discomfort, and even urinary retention; listlessness, sallow complexion, fear of cold and cold limbs; pale and moist tongue, thin white coating, deep and thready pulse.

[0087] 3. Inclusion criteria and exclusion criteria

[0088] Meet the following requirements: ① Those who meet the diagnostic criteria of Western medicine and traditional Chinese medicine; ② Male patients aged 50 - 80 years old; ③ Have not used drugs to treat BPH in the past 1 month; ④ Exclude severe ones; ⑤ Exclude the possibility of prostate cancer; ⑥ Voluntarily participate and sign the informed consent form.

[0089] 4. Exclusion criteria

[0090] ① Those who do not meet the inclusion criteria; ② Those with other urogenital system diseases at the same time, such as prostatitis, neurogenic bladder, urethral stricture, etc.; ③ Those who have undergone prostate surgery or other special treatments; ④ Those with various chronic diseases, psychiatric patients, and those with abnormal liver and kidney functions; ⑤ Those allergic to the observed drugs; ⑥ Those allergic to this drug or those who do not take the medicine as prescribed, and those with various reasons affecting the judgment of efficacy or safety; ⑦ Those who have not participated in other clinical trials.

[0091] 5. Case exclusion, dropout and withdrawal criteria

[0092] 5.1 Dropout criteria: ① Those who cannot adhere to treatment, regular follow-up, and have poor compliance; ② Those who have severe complications and adverse reactions during the implementation of the project; ③ Those who do not take the medicine according to the project design regulations or take other drugs for treating BPH without permission; ④ Those who actively request to withdraw from the project researchers.

[0093] 5.2 Exclusion and withdrawal criteria: ① Cases with poor patient compliance; ② Those who do not treat according to regulations; ③ Those who have severe adverse events during the observation period and are not suitable to continue treatment; ④ Those who request to withdraw from the experiment by themselves due to other reasons.

[0094] 6. Research methods

[0095] 6.1 Treatment methods

[0096] Both groups of patients were given Western medicine capsules (α - receptor blocker or combined with 5α - reductase inhibitor), 0.2mg / time, 1 time / day, orally before going to bed. The observation group was combined with Qianlong Shutong Prescription on the basis of Western medicine treatment, 1 dose / time, twice a day, morning and evening, orally. This observation takes 12 weeks as a course of treatment, and is continuously applied for one course.

[0097] 6.2 Observation indicators

[0098] 6.2.1 International Prostate Symptom Score (IPSS)

[0099] The patient's prostate condition is assessed. The total score ranges from 0 to 35, with the higher the score, the more severe the symptoms.

[0100] 6.2.2 Quality of life score (QOL)

[0101] Assess the extent to which the quality of life of BPH patients is impaired due to disease symptoms. The score ranges from 0 to 6, and the higher the score, the worse the quality of life.

[0102] 6.2.3 Urodynamic indicators

[0103] Including Maximum flowrate (Qmax) and residual urine volume of bladder (RUV). This study compared the improvement of the two indicators before and after treatment in the two groups of patients. The smaller the Qmax and the larger the RUV in the same group, the more severe the symptoms.

[0104] 6.2.4 TCM Syndrome Score

[0105] The main symptoms include dysuria, frequent urination, soreness of waist and knees, and secondary symptoms include pale complexion, chills, cold limbs, fatigue, and increased nocturia. The higher the score, the more severe the symptoms.

[0106] 6.2.5 Observation and treatment of adverse events

[0107] During the treatment period, the two groups of patients had regular follow-up visits (every 2 weeks) to evaluate the effect of the medication and whether there were any adverse reactions. If any adverse reactions were found, symptomatic treatment was given and relevant indicators were dynamically monitored. If necessary, the study of the patient could be terminated early, and relevant records and analysis were kept.

[0108] 6.2.6 Clinical efficacy criteria

[0109] Formulated with reference to the "Guidelines for Clinical Research of New Chinese Medicines" (2002 edition): ① Significantly effective: IPSS score or (and) total score of TCM syndromes decreased by more than 70%. ② Effective: IPSS score or (and) total score of TCM syndromes decreased by more than 30%. ③ Ineffective: score decreased by less than 30% or did not improve, and clinical symptoms did not ease. Total effective rate = (significantly effective + effective) cases / total number of cases × 100%.

[0110] 7. Results

[0111] 7.1 Shedding and Removal

[0112] A total of 12 cases were lost and excluded during the trial (7 cases in the observation group who did not adhere to the full course of medication; 5 cases in the control group who did not adhere to the full course of medication). Finally, 148 effective cases were included in the subsequent evaluation, 73 cases in the observation group and 75 cases in the control group.

[0113] 7.2 Statistical Results

[0114] When comparing the IPSS score, QOL score, Qmax, and RUV within each group before and after treatment, the differences were statistically significant (P < 0.01); when comparing the IPSS, QOL, Qmax, and RUV scores of the observation group with those of the control group (see Figure 9 ), the differences were significant (P < 0.05); when comparing the TCM syndrome scores within each group of the two groups, they all decreased, with statistical differences (P < 0.01); when compared with the control group after treatment (see Figure 8 ), the differences were significant (P < 0.05), especially in improving the symptoms of fear of cold and cold limbs, fatigue, dizziness, and tinnitus, which were superior to the control group (P < 0.05); after 12 weeks of treatment, the total effective rates of TCM syndromes in the observation group and the control group were 93.15% (68 / 73) and 68.00% (51 / 75) respectively, and the differences were significant (P < 0.01), and no obvious adverse reactions were observed in both groups.

[0115] 8. Safety

[0116] No obvious adverse reaction events occurred in both groups of patients during the treatment.

[0117] 9. Typical Cases

[0118] Zhu XX, male, 65 years old. The patient had symptoms of frequent urination, urgency of urination, and dysuria for more than 3 months. There was no hematuria or dysuria, no fear of cold or fever, nausea, vomiting, abdominal pain, or diarrhea. Symptoms included frequent urination, urgency of urination, and dysuria; the tongue was pale, the coating was white, and the pulse was slippery. Since the onset of the disease, the patient's sleep, diet, and spirit were normal, the stools were normal, and the urination was as described above, and the weight had not changed significantly. After continuously taking this drug for more than 3 months, the above symptoms were significantly alleviated, and the quality of life and symptom scores returned to the normal range.

[0119] Zhang XX, male, 66 years old. The patient had intermittent dysuria for more than 6 years. Associated with urgency and frequency of urination, no gross hematuria was seen, no obvious gross hematuria, no fever or aversion to cold, no nausea, vomiting, no dizziness, headache, no shortness of breath or difficulty breathing, no abdominal distension or pain, etc. Since the onset of the disease, the patient's sleep, diet, and spirit were normal, the stools were normal, and the urination was as described above, and the weight had not changed significantly. The tongue was pale, the coating was white, and the pulse was slippery. After continuously taking this drug for more than 3 months, the above symptoms were significantly alleviated, and the quality of life and symptom scores returned to the normal range.

[0120] In summary, after the treatment of benign prostatic hyperplasia with the traditional Chinese medicine composition and its preparations of the present application, compared with the commonly used α-blockers or combined 5α-reductase inhibitors for the treatment of benign prostatic hyperplasia, patients are less likely to experience orthostatic hypotension, erectile dysfunction, etc. It is superior to the treatment with pure western medicine in terms of relieving the prostatic symptoms of patients, improving the quality of life, and alleviating the lower urinary tract symptoms. Moreover, the improvement of the traditional Chinese medicine syndrome scores is more significant than that of the treatment with pure western medicine, especially in relieving the symptoms of soreness and weakness in the waist and knees, fatigue, and aversion to cold and cold limbs.

Claims

1. A composition for treating benign prostatic hyperplasia, characterized in that, By weight, its components are: 15-20 parts of Flemingia philippinensis, 6-9 parts of Curcuma zedoaria, 12-15 parts of Eucommia ulmoides, 9-12 parts of Achyranthes bidentata, 12-15 parts of Codonopsis pilosula, 15-20 parts of Astragalus membranaceus, 6-9 parts of Cinnamomum cassia, 10-12 parts of Curculigo orchioides, 10-12 parts of Epimedium brevicornu, 12-15 parts of Phellodendron amurense, 10-15 parts of Poria cocos, 10-12 parts of Paeonia suffruticosa, 10-15 parts of Paeonia lactiflora and 10-15 parts of Prunus persica.

2. The composition according to claim 1, characterized in that, By weight, its components are: 15 parts of Flemingia philippinensis, 6 parts of Curcuma zedoaria, 15 parts of Eucommia ulmoides, 9 parts of Achyranthes bidentata, 12 parts of Codonopsis pilosula, 15 parts of Astragalus membranaceus, 6 parts of Cinnamomum cassia, 10 parts of Curculigo orchioides, 10 parts of Epimedium brevicornu, 12 parts of Phellodendron amurense, 10 parts of Poria cocos, 10 parts of Paeonia suffruticosa, 10 parts of Paeonia lactiflora and 10 parts of Prunus persica.

3. A preparation for treating benign prostatic hyperplasia, characterized in that, Using the components of the composition according to claim 1 or 2 as raw materials, common Chinese patent medicine preparations are made according to conventional processes.

4. The preparation according to claim 3, characterized in that: The Chinese patent medicine preparation is a liquid preparation, a semi-solid preparation or a solid preparation.

5. The preparation according to claim 3, characterized in that: The dosage form of the Chinese patent medicine preparation is a decoction, an extract, a pill, a tablet, a granule or a capsule.

6. The preparation method of the preparation according to claim 3, characterized in that, Including: Mix the above raw materials, soak them in water, then decoct them. After decocting, take the medicinal liquid. The obtained medicinal liquid is a decoction, or the obtained medicinal liquid is further processed into other Chinese patent medicine preparations according to conventional processes.

7. The preparation method according to claim 6, characterized in that: When soaking in water, the added water is 5-15 times the total weight of the raw materials.

8. The preparation method according to claim 6, characterized in that: When soaking in water, the soaking time is 20-60 minutes.

9. The preparation method according to claim 6, characterized in that: The number of decocting times is 1-3 times, 1-2 hours each time. After filtration, the filtrates are combined to obtain the medicinal liquid.

10. Use of the composition according to any one of claims 1-2, the preparation according to any one of claims 3-5 or the preparation obtained by the preparation method according to any one of claims 6-9 in the preparation of a drug for treating benign prostatic hyperplasia.

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