Natural remedy made from Drymis winteri var. chilensis for the treatment of prostate problems

Abstract

The present invention relates to the use of a therapeutically effective amount of an aqueous extract of Drymis winteri var. Chilensis for the manufacture of a natural remedy for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas, which is to be administered orally or nasally. and a procedure for treating problems of the prostate such as prostatitis, benign prostatic hyperplasia or malignant prostate cancer in a patient, wherein the procedure includes the following: - Administration of the natural remedy produced from the aqueous extract according to the invention to the patient for the treatment of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas for a period sufficient to treat prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas.

Description

[0001] The present invention relates to the use of a therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis for the manufacture of a natural remedy for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas, which is to be administered orally or nasally, according to claim 1, and a method for treating prostate problems using the therapeutically effective amount of the aqueous extract of Drymis winteri var. chilensis according to claim 8. Background of the invention

[0002] Modern medicine and its underlying scientific apparatus are constantly searching for new, effective drugs to prevent, treat, or delay the progression of cancer. The goal is to cure the diseases caused by cancer. The present invention is intended, in particular, to provide a new healing method or a new natural remedy for the treatment of prostate problems, primarily complementing or advantageously replacing established conventional medical treatments for prostate problems. The primary aim is to approach the cure of, for example, prostate cancer or other types of cancer from a completely new perspective by combining traditional and modern medicine. The use of herbal medicines and folk remedies has been known for thousands of years.For a long time, Western medicine considered herbal approaches to treating numerous diseases, such as viral infections, arthritis, and cancer, to be ineffective and dangerous. However, during the 19th century, many home remedies containing plants were patented and sold. Modern pharmaceuticals have since replaced these well-known remedies, although a large number of modern drugs still contain plant- or animal-derived ingredients. Currently, natural remedies and folk medicines are of increasing interest to conventional medicine in order to develop or re-establish new or "old" methods for the therapy and treatment of diseases.

[0003] The present invention addresses this growing interest in natural medicine and ethnomedicine by disclosing an aqueous extract obtained from the plant Drymis winteri var. chilensis for the production of a natural remedy for the treatment of prostate problems. The prostate, also known as the prostate gland, is an organ located in the lower pelvic region of men, surrounding the urethra.

[0004] Possible diseases and problems of the prostate include prostatitis (inflammation of the prostate), benign prostatic hyperplasia (BPH), or malignant prostate cancer, which, with 62,000 new cases per year, is the most common type of cancer in men in Germany (Robert Koch Institute, June 3, 2024).

[0005] The risk of prostate enlargement increases from the age of 50; in Germany, up to 70% of men over 70 are affected. Besides lifestyle factors, genetic predisposition also plays a significant role in the risk of developing prostate cancer. The PSA level, in particular, is crucial for patients with prostate cancer and its early detection. Men with advanced prostate cancer are often older and have other health conditions, which can influence the appropriate treatment.

[0006] The determination of the PSA (prostate-specific antigen) level has become the established traditional diagnostic method for the early detection of prostate cancer. Prostate-specific antigen is a protein produced by the cells of the prostate gland. PSA is found in blood serum and semen.

[0007] An elevated PSA level can be caused by the following symptoms: • Prostate cancer • Prostatitis (inflammation of the prostate) • Benign prostatic hyperplasia • Taking medications (tamsulosin, alfuzosin, doxazosin, terazosin, silodosin, finasteride, dutasteride, atropine, tolterodine, oxybutynin, darifenacin, soliteacin, fesoterodine, trospium), or taking dietary supplements • Pressure on the prostate: cycling, horseback riding, prostate exam at the urologist • Urinary tract infection or inflammation • Sex and ejaculation, before the test

[0008] There is no real normal value, as this always has to be assessed individually (e.g. depending on age), however, further investigation is required from 4 ng / ml.

[0009] Since the beginning of 2023, there have been a number of innovations in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC): The EAU has updated its guideline on the treatment of prostate cancer.

[0010] Prostate cancer is among the cancers that often grow slowly and do not always pose an immediate threat to those affected. Furthermore, an increasing number of tumors are being detected at a very early stage, meaning that treatment may be initiated even though the cancer would never have caused any problems. Therefore, it is essential to weigh whether the benefits of treatment are proportionate to its risks and expected side effects. For this reason, watchful waiting strategies play an important role in the treatment of prostate cancer. Two different approaches are distinguished: 1. watchful waiting and 2. Active Surveillance. 1. Wait-and-see approach

[0011] In watchful waiting, the tumor is not treated initially, regardless of its stage. Palliative treatment only begins if symptoms develop. For patients whose tumor could potentially be cured, watchful waiting should only be considered if their life expectancy is less than ten years due to age or other illnesses and their Gleason score is no higher than 7 (see active surveillance). 2. Active monitoring

[0012] In active surveillance, patients are closely monitored so that curative treatment can be initiated in a timely manner if necessary. If the tumor remains asymptomatic, no treatment is administered. However, if disease progression is indicated, a radical prostatectomy is usually performed, or alternatively, radiation therapy. An MRI scan should be performed before deciding on active surveillance.

[0013] Active surveillance is also suitable for younger patients without other serious illnesses who meet the following criteria: • PSA level <_ 10 ng / ml • Gleason score ≤6 • locally confined prostate cancer (cT1-2a), • Tumor in ≤2 cores (out of 10-12 cores) • Tumor infestation per punch ≤50%

[0014] Regular checkups include PSA testing and a digital rectal examination every three months. Regular MRI scans are now also part of active surveillance. If the PSA level remains stable for two years, the interval between checkups can be extended to six months. In addition, a follow-up biopsy should be performed after six months. If a targeted biopsy with MRI was performed before the decision to initiate active surveillance, the first follow-up biopsy should not be performed until one year later. After that, it is recommended to checkups every 12 to 18 months for the next three years, and then every three years if the PSA level remains stable.

[0015] If the inclusion criteria for one criterion are no longer met, or if the PSA doubling time decreases to less than three years, discontinuation of active surveillance should be recommended. Of course, the patient can always decide to discontinue observation and actively treat the tumor. Similarly, switching to watchful waiting may be appropriate if the estimated life expectancy is less than 10 years. Disclosure of the invention

[0016] The present invention aims to address the healing of prostate problems from a completely new perspective, whereby the treatment methods established by conventional medicine for prostate problems can be supported by the use of a natural remedy and can be substituted in a particularly advantageous way while preserving the prostate.

[0017] The present problem is solved by using a therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis for the manufacture of a natural remedy for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas, which is to be administered orally or nasally, and by a method for treating prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas in a patient by administering a therapeutically effective amount of the aqueous extract of Drymis winteri var. chilensis according to the invention.

[0018] Drymis winteri var. chilensis, commonly known as Canelo, is a sacred plant for the indigenous Mapuche people, who use the aerial parts of this plant to treat various ailments, including digestive problems such as flatulence, colic, and stomach aches. For toothaches and skin irritations, Canelo is sometimes applied directly to the affected areas. Extracts from the stem bark are also known to be used to treat human and cattle diseases, such as gastrointestinal nematodes and rheumatic conditions. In the past, the stem bark of Drymis winteri var. chilensis was exported to Europe as an antiscorbutic drug. Phytochemical studies of extracts from the aerial parts of Drymis winteri var. chilensis were conducted in Chile several decades ago (Appel et al., 1964; Appel et al.)., 1960; Brown, 1994) report on phytonutrients and pest repellents (Jansen & de Groot, 2004; Zapata et al., 2009; Monsalvez et al., 2010). Phytochemical reports on the chemical composition of continental Drymis winteri var. chilensis indicate the presence of tannins, flavonoids, essential oils, Driman-type sesquiterpenes, sesquiterpene lactones (Muñoz et al., 2001), lignans, and phytosterols (Muñoz et al., 2015). Driman-type sesquiterpenes or terpenoids possess a variety of biological activities, including antimicrobial, antibacterial, antifungal, anti-septic, cytotoxic, molluscicidal, piscicidal, growth-regulating and phytotoxic properties (Jansen & de Groot, 2004).

[0019] Preferably, according to the present invention, the aqueous extract is produced from the aerial parts of the plant Drymis winteri var. chilensis, such as the bark. Particularly preferably, the aerial parts are the leaves of the plant Drymis winteri var. chilensis, from which the aqueous extract according to the invention is obtained for the production of a natural remedy for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia, or malignant prostate cancer.

[0020] Advantageously, the leaves of the plant Drymis winteri var. chilensis are dried before the production of the aqueous extract according to the invention. This has the particular advantage that the leaves are harvested in the plant's country of origin and dried in preparation for transport. In addition to simplified transport, drying the leaves advantageously prevents spoilage or pest infestation during transport. However, it is also conceivable, although this would entail increased transport costs, to freeze the leaves of the plant Drymis winteri var. chilensis directly after harvesting and advantageously shock-freeze or freeze-dry them, so that they can then be transported to the respective destination under refrigeration.At the destination itself, a decision can then be made as to whether the leaves should be dried to produce an aqueous extract by brewing them with water, or whether the leaves, after being removed from refrigeration, should be freshly crushed, for example, to obtain an aqueous extract for the production of a natural remedy for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas, which is to be administered orally or nasally.

[0021] For simplified administration of the aqueous extract according to the invention from the plant Drymis winteri var. chilensis, regardless of whether the extract was obtained from dried or freeze-dried aerial parts of the plant, the resulting natural remedy can advantageously be offered in the form of a tea, a tablet, a lozenge, chewing gum, an active ingredient capsule, a concentrated solution, or a gel, and taken and absorbed orally. Particularly when administered via an active ingredient capsule or tablet, a sustained release of the natural remedy after oral ingestion can be achieved through the type of capsule or the composition of the tablet. This allows the amount of 0.4 g of leaves used in the clinical evaluations, with an active ingredient content in the range of 10 mg / day to 200 mg / day, to provide the therapeutically effective amount of the aqueous extract of Drymis winteri var.The traditional method of administering this natural remedy, which is typically achieved through five infusions, can be replaced by a single oral dose of a capsule or tablet, as the ingredients are released gradually throughout the day from the capsule or by dissolving from the compounds in the tablet. Ideally, the natural remedy is made available to the market, and especially to the patient, in a concentrated solution, and even more preferably in a highly concentrated solution in ampoules or dropper bottles, to facilitate administration and ingestion.This has the advantage that the patient only needs to receive a few drops orally pipetted daily or several times a day to ingest the therapeutically effective amount of the natural remedy according to the invention for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas orally, for example by oral administration under the patient's tongue.

[0022] In addition to constituents such as tannins, flavonoids, lignans, and sesquiterpene lactones, the aqueous extract from the dried leaves of the plant *Drymis winteri* var. *chilensis* advantageously contains sesquiterpenes, essential oils, and / or lignans as its main components. Furthermore, the aqueous extract advantageously contains phytosterols and, additionally, their reduced form, known as phytostanols. In particular, β-sitosterol has been detected in the aqueous extract from the dried leaves of *Drymis winteri* var. *chilensis*. β-Sitosterol is a sterol commonly found in plants, which has gained particular importance due to its inhibitory effect in benign prostatic hyperplasia (BPH). The weight percentage of essential oils in the aqueous extract from the dried leaves of the plant Drymis winteri var. chilensis is advantageously between 0.20% (w / w) and 0.30% (w / w) and particularly advantageously between 0.23% (w / w) and 0.26% (w / w).In addition to their antimicrobial, fungicidal, and insecticidal properties, the essential oils also have beneficial analgesic effects. The lignans and their synthetic derivatives, which are among the main components of the aqueous extract of the plant *Drymis winteri* var. *chilensis*, have attracted increasing interest in cancer chemotherapy and other pharmacological applications. The sesquiterpenoids of the *Drymis winteri* var. *chilensis* found in the aqueous extract of *Drymis winteri* var. *chilensis* possess a wide range of biological activities, including antimicrobial, antibacterial, antifungal, anti-putrefactive, cytotoxic, molluscicidal, piscicidal, growth-regulating, and phytotoxic properties.

[0023] The lignan sesamin, found in the aqueous extract of the dried leaves of the plant *Drymis winteri* var. *chilensis*, is already highly valued as an insecticide for protecting building materials from unwanted insect infestation. Since some lignans possess strong antimicrobial, antifungal, antiviral, antioxidant, and insecticidal properties, they likely play an important role in plant defense against various biological pathogens and pests. Sesamin has been shown to inhibit the enzyme delta-5-desaturase in the synthesis of polyunsaturated fatty acids and is thus effective against inflammation.

[0024] The applicant of the present invention attributes the excellent results in the treatment of prostate problems (see clinical evaluation) with the natural remedy prepared from the aqueous extract of the plant Drymis winteri var. chilensis to the synergistic effects of the constituents in the aqueous extract from the dried or freeze-dried leaves of this plant. Based on the positive clinical evaluation, the applicant of the present invention intends to further elucidate the synergistic effects of the constituents in the aqueous extract from the dried leaves of the plant Drymis winteri var. chilensis scientifically, in order to gain insights for the chemical synthesis of a pharmaceutical that, in addition to the aqueous extract according to the invention from the dried or freeze-dried leaves of the plant Drymis winteri var.chilensis may be used in conventional medicine in the future to treat prostate problems, with a primary focus on preserving the prostate. Clinical evaluation

[0025] An aqueous extract in the form of tea was prepared by brewing 0.4 g of dried leaves of the plant *Drymis winteri* var. *chilensis* with 200 ml of water. The tea was administered orally to a patient with confirmed prostate cancer diagnosed as pT1c, Nx, Mx, 1 / 13 positive. Throughout the day, the previously brewed leaves were again steeped in 200 ml of water to produce an aqueous extract in the form of tea. This second extract was also administered orally to the patient. The brewing process of the leaves, which had already been steeped multiple times, was repeated several times throughout the day, ensuring that the patient received an aqueous extract in the form of tea from the dried leaves of *Drymis winteri* var. *chilensis* at least five times a day. The oral administration of at least five aqueous extracts in the form of tea from the dried leaves of *Drymis winteri* var. *chilensis* every day was intended to be effective.The treatment of *Arabidopsis chilensis*, starting with 0.4 g of dried leaves each day to obtain aqueous infusion extracts, was carried out over a period of 6 months. After this period, the first clinically significant improvements in the patient, namely a regression of the prostate carcinoma, could be clearly demonstrated.

[0026] A second patient with a significantly enlarged prostate and a PSA level of 11 ng / ml due to prostatitis was given 200 ml of an aqueous extract, prepared as a tea, orally four times daily for four months. This extract was made by steeping 0.4 g of dried leaves of the plant *Drymis winteri var. chilensis* in 200 ml of hot water. After just six weeks, a significant reduction in the size of the prostate was clinically observed, along with a decrease in the PSA level to 7 ng / ml. After four months of oral administration of the aqueous extract, the PSA level was clinically measured at 1.23 ng / ml. Clinical examination of the prostate revealed that it had returned to its natural size.

[0027] A third patient with a clinical diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) was also given 200 ml of an aqueous extract in the form of tea orally for a period of 4 months as an adjunct to testosterone deprivation therapy for metastatic hormone-sensitive prostate cancer. This extract was prepared by brewing 0.4 g of dried leaves of the plant *Drymis winteri var. chilensis* with 200 ml of hot water. In addition to the reduction of the primary tumor in the prostate, a significant decrease in clinically diagnosed metastases was observed.

[0028] Currently, further clinical studies are being conducted on a total of 5 patients following the procedure described above, with all patients already showing an improvement in prostate problems compared to the initial clinical findings.

[0029] Since no side effects have been reported in the literature or observed in clinical evaluations following oral administration of the aqueous extract or natural remedy according to the invention, the aqueous extract or natural remedy according to the invention derived from the plant Drymis winteri var. chilensis may be advantageously indicated for the prevention of prostate problems. This means that the aqueous extract or natural remedy according to the invention could be recommended for daily intake by men to prevent prostate problems.

[0030] Finally, another aspect of the present invention is a method for treating prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas in a patient, wherein the method comprises: - Administration of the natural remedy produced from the aqueous extract according to the invention to the patient for the treatment of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas for a period sufficient to treat prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas.

[0031] As already described for the use of the therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis according to the invention for the production of a natural remedy for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia, or malignant prostate carcinomas, which is to be administered orally or nasally, oral administration can be in the form of a tea, tablet, lozenge, chewing gum, capsule, or gel. The duration of administration, the frequency of oral intake, and the daily dosage must be evaluated and adjusted based on multiple factors. For example, the type of prostate problem, the patient's age and weight, and their lifestyle must be taken into account to determine the therapeutically effective amount of the aqueous extract according to the invention.

[0032] Taking into account the above criteria, a daily dosage can therefore advantageously range between 10 mg / day and 200 mg / day.

[0033] In order to avoid further repetition regarding the advantages of the inventive method, reference is made to the description of the use of the therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis according to the invention for the production of a natural remedy for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas, which is to be administered orally or nasally, and full reference is made to the disclosure by this description and vice versa.

Claims

[1] Use of a therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis, for the manufacture of a natural remedy for the treatment or prevention of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate cancer, to be administered orally or nasally. [2] Use of a therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis according to claim 1, wherein the extract can be produced from the aerial parts of the plant Drymis winteri var. chilensis. [3] Use of a therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis according to claim 2, characterized by that the above-ground parts are the leaves of the plant Drymis winteri var. chilensis. [4] Use of a therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis according to claim 3, characterized by, that the dried leaves of the plant Drymis winteri var. chilensis are steeped in the aqueous extract. [5] Use according to claim 4, wherein the natural remedy containing the extract is in the form of a tea, a tablet, a lozenge, a chewing gum, an active ingredient capsule, a highly concentrated solution or a gel. [6] Use of a therapeutically effective amount of an aqueous extract from the plant Drymis winteri var. chilensis according to any of the preceding claims, wherein the extract contains at least sesquiterpenes, essential oils and / or lignans. [7] Use of a therapeutically effective amount of an aqueous extract of Drymis winteri var. chilensis according to any of the preceding claims, wherein the extract contains sesamin as a lignan. [8] Procedures for treating prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate cancer in a patient, wherein the procedure includes: - Administration of the natural remedy prepared from the aqueous extract according to one of the preceding claims to the patient for the treatment of prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas for a period sufficient to treat prostate problems such as prostatitis, benign prostatic hyperplasia or malignant prostate carcinomas. [9] Method for treating prostate problems according to claim 8, wherein the aqueous extract contains a therapeutically effective amount of at least one of the therapeutically effective ingredients mentioned in claims 5 and 7. [10] Method according to claim 8, wherein the therapeutically effective amount is a daily dosage in the range of about 10 mg / day - 200 mg / day.