WO2018222164A9

WO2018222164A9 - Use of an herbal formula containing pumpkin seed oil in bph treatment

Info

Publication number: WO2018222164A9
Application number: PCT/TR2018/050068
Authority: WO
Inventors: Mevlüt Büyükhelvacigi̇l
Original assignee: Helvacizade Gida Ilac Kimya Sanayi Ve Ticaret AS
Current assignee: Helvacizade Gida Ilac Kimya Sanayi Ve Ticaret AS
Priority date: 2017-02-28
Filing date: 2018-02-26
Publication date: 2019-05-02
Anticipated expiration: 2019-08-28
Also published as: WO2018222164A2; WO2018222164A3; TR201703079A2

Abstract

In the pharmaceutical industry, the present invention is related to the use of an herbal formulation in the form of a soft capsule having antioxidant properties, prepared with pumpkin seed oil particularly rich in terms of essential fatty acids content in the treatment BPH (Benign Prostate Hyperplasia). Said herbal formulation comprises pumpkin seed oil, dl α-tocopherol, dl α-tocopheryl acetate, glycerin, distilled water, and gelatin which provide the integrity of the contents and capsule formation.

Description

TECHNICAL FIELD

The present invention is related to the use of an herbal formulation comprising the pumpkin seed oil (Oleum Cucurbitae semen) in the pharmaceutical industry in the chemical industry.

In particular, the invention is related to the use of an herbal formulation in treatment of BPH (Benign Prostate Hyperplasia/benign prostatic growth) in the form of a soft capsule with antioxidant feature prepared with pumpkin seed oil which is rich in terms of essential fatty acids.

STATE OF THE ART

Essential fatty acids are the fatty acids that cannot be synthesized within the body and which should be taken from the outside in order to maintain the organism's life. These essential fatty acids should be taken into the organism via nutrients or by certain supplements. Essential fatty acids taken from the outside into the organism, serve as assistants to the treatment of BPH (Benign Prostate Hyperplasia/benign prostate growth).

In the present art; within the products that are used as assistants to treat BPH (Benign Prostate Hyperplasia/benign prostatic hyperplasia) synthetic substances or chemicals in certain proportions are present. The use of synthetic and chemical substances causes many side effects within the organism and affects many systems of the body badly.

Also, products are in liquid form within most of the current implementations. This situation makes it difficult to carry out controlled dosing. Therefore, required dosage cannot be provided completely and clearly.

One of the related patents in the literature is the application no. C 105981810. The present invention mentions yeasted yoghurt made from the mixture comprising many herbal products as well as pumpkin seed extract, water and high proportion of milk, which regulates blood pressure, activates spleen and kidney, assists in constipation treatment and has anti-aging effect. Application no. CN102908544 which is in the present art refers to a formulation which is good for heart health, which is made by mixing a lot of herbal materials proportionally, such as pumpkin seed, and mentions preparation technique of said formulation by boiling.

As a result, due to the above described drawbacks and the inadequacy of the current solutions, a technical field development of BPH (Benign Prostate Hyperpiasia/benign prostate growth) of pumpkin seed oil has become essential. OBJECT OF THE INVENTION

The main object of the invention is to provide an herbal formulation containing pumpkin seed oil (Oleum Cucurbitae semen) to help in the treatment of BPH (benign prostatic hyperpiasia/benign prostate growth). Pumpkin seed oil inhibits 5-a reductase enzyme. It has been reported it inhibits the conversion of testosterone into dihydrotestosterone (DHT) thereby assisting in the treatment of prostate gland related diseases.

Pumpkin seed oil prevents urinary incontinence by loosening the bladder muscles when the bladder is filled with nitric oxide. Due to these dual effects on pelvic muscles and nitric oxide, pumpkin seed oil reduces incontinence. Pumpkin seed oil can also be used as an adjunct to treatment of urinary tract infections, especially cystitis.

Another object of this invention is to ensure that the formed formulation is 100 % natural and herbal content without comprising any chemicals. Even when the pumpkin seed oil used in the formulation is obtained, no heat treatment or chemical treatment is applied. So; the active substances, nutritional values and minerals within the plant, pass directly to the product without getting lost.

Another object of this invention is to provide reducing the side effects that affect human health to a minimum, thanks to the content created without the chemicals. Side effects that affect only the gastrointestinal system such as nausea, vomiting and diarrhea, are observed very rarely with the use of completely natural and herbal products.

Another object of the present invention is to provide ease of use in terms of patient compliance, with the created formulation being in capsule form. Also, thanks to created capsule form, it is advantageous to obtain dosing in said indications. DETAILED DESCRIPTION OF THE INVENTION

The preferred use of an herbal capsule formulation obtained using pumpkin seed oil to achieve the object of this invention is disclosed only for the sake of better understanding of the present invention and without any limiting effect.

Pumpkin Seed Oil:

Pumpkin seed oil has been used for centuries as an herbal medical product. Pumpkin seed oil shows many different pharmacological effects due to the wide variety of substances within the composition and to the different therapeutic activities of each.

Pumpkin seeds; are rich in terms of phytosterois, tocopherols and essential fatty acids (mostly iinoleic and oleic acid) and the active components within the pumpkin seeds are Δ7- sterois (avenasterol and spinasterol) and A5-sterols (sitosterol, stigmasterol). Pumpkin seed oil inhibits 5-a reductase enzyme, it has been reported it inhibits the conversion of testosterone into dihydrotestosterone (DHT) thereby assisting in the treatment of prostate gland related diseases.

Many nonclinical and clinical studies have been conducted to investigate the effects of pumpkin seed oil on benign prostatic hyperplasia, in clinical trials, it has been shown that pumpkin seed oil can be used in a clinically safe manner to aid in the treatment of benign prostatic hyperplasia.

Pumpkin seed oil has been used for many years as an adjuvant to antihelminthic (schistosomiasis, tapeworm, etc.) treatment, in a clinical trial, it has been shown that pumpkin seeds may be helpful for Schistosomiasis, a serious parasitic disease that spreads through snails primarily in Asia and Africa. Also, it has been reported that pumpkin seeds may be helpful in the treatment of tapeworms. Capsule formulation content:

In the formulation, pumpkin seed oil is used as the active substance and di a-tocophero!, di a-tocopheryi acetate, glycerin, purified water and gelatin are used as auxiliary substances, di a-tocopherol and dl a-tocopheryi acetate are used as protecting agents. In said formulation, di a-tocopheroi, di a-tocopheryl acetate are added at ppm level. For gelatin used to provide the integrity of the content, beef gelatin is used. As an alternative to gelatin, other animal- derived and herbal gelatins can be used. As indicated in Table 1 , 42.635% pumpkin seed oil; 0.0030% dl a-tocopherol; 0.0213% dl tocopheryl acetate; 10,723% glycerin; 23,312% water; 23,312% gelatin by weight, are used

Table 1. Content of the capsule and percentages by weight

The manufacturing steps of the capsule formulation are as follows: the pumpkin seed, one of the raw materials, is subjected to sieving. Breaking process is performed if necessary after the sieving process. The pumpkin seed is sent to the cold press unit after said processes and after the desired size is obtained. The process of oil removal from the raw material is carried out by the cold press method. In said method, 55°C should not be exceeded. The oil from the cold press unit is kept in mixing and resting tanks prior to filtration. Thus, it is easy to separate the possible particles by mixing and resting processes.

Extracted oil; after mixing and resting tanks, is fed to the filter unit indoors and at room temperature. In the filter unit, the particles, if any in the oil content are filtered. After the filtration step, dl α-tocopherol as a preservative and dl a-tocopheryl acetate as a preservative are added to the obtained oil. Thus, the mixture forming the content is obtained.

While these operations are being performed, on the other hand in the gelatin preparation unit, gelatin used to provide capsule integrity is prepared.

Following the formation of the mixture and the preparation of the gelatin, capsules are prepared at the desired dosage by dispensing to the capsule production unit. Said capsule is soft gelatin capsule. After the capsule is prepared, drying is carried out. Dried capsules are packed. Ca^sule Usa^

Therapeutic indications

The capsule is rich in terms of essential (basic) fatty acids content. It is used to help treating BPH (Benign Prostate Hyperplasia).

Dosage and Application ethod

• Dosage administration frequency and duration: if not otherwise recommended by the doctor; in adults, 1-3 capsules (960-2880 mg/day dose) are taken orally 3 times a day.

^» Method of administration: Capsules should be swallowed with sufficient water without crushing or chewing in mouth, preferably in full stomach.

Additional Information on Speciai Popuiations:

• Kidney/liver failure: This should not be used in these patient groups as there is no adequate safety study in kidney and liver patients.

^« Pediatric population: The capsule should be used for under the age of 18 in children and adolescents under physician control.

• Geriatric population: There are no studies conducted in the elderly. Contraindjcations

- It should not be used when there is an allergy to the active substance or any component of the capsule,

- During pregnancy and breastfeeding,

- In patients with liver and kidney failure.

Special Warnings and Precautions for Use Patients using oral anticoaguiant drug should not exceed 3 g daily dose of capsules.

Each capsule contains 0.0805 g glycerin. However, no side effects due to glycerin are expected at this dose.

Consult your doctor or pharmacist if you experience symptoms such as fever, spasm, blood in your urine, painful urination, or urinary retention during your capsule use.

It is recommended to continue using the capsule longer than 2 months in consultation with the doctor.

^» General Recommendation: Women with childbearing potential/should not be used because there is no study related to contraception.

• Pregnancy period: Clinical data on exposure to pumpkin seed oil in pregnancies are not available. Studies in animals are inadequate with regard to pregnancy and/or embryonal/fetal development and/or postnatal and/or postnatal developmental effects. The potential risk to people is unknown. There is no adequate information on its use with oral contraceptive drugs. Since its safety is not shown in pregnancy, it is not recommended to use the capsule during pregnancy.

• Lactation period: Since its safety in lactation is not shown, it is not recommended to use the capsule in lactation.

Undesired Affects

• Gastrointestinal Diseases: Common nausea, vomiting, diarrhea. Apart from these, no undesirable effect has been reported to date.

Overdose

No overdose has been reported until today with regard to pumpkin seed oil. Pumpkin seed oil, which is used orally, can be well tolerated, without any effect due to overdose. However, if any signs of overdose are present, treatment should be symptomatic and supportive. There is no method to increase a specific antidote and its elimination. Storage Conditions

The shelf life of the product is 2 years. The capsule, content and production methods of which mentioned above, has been licensed by Republic of Turkey Ministry of Health authorities as "Traditional Herbal Medical Product". Said license has the order number 2018/825 dated 21 st of November 2016; called ZADE VITAL CUCURMIN 320 mg as a soft capsule. According to the above listed Indications and Traditional Herbal Medicine Product Directive, it is a Traditional Herbal Medicine Product LICENSED by Republic of Turkey Ministry of Health. There are products containing numerous synthetic chemicals licensed for indications specified in the market. However, there is no traditional herbal medical product in this area with such an indication licensed by health authorities.

In the majority of current applications; while production in poor hygiene conditions is matter of concern, related formulation is produced under GMP (Good Manufacturing Practices) norms, which the Ministry of Health requests from the pharmaceutical factories.

As known, it is a very difficult operation to provide standardization in herbal products. Within the related formulation;

· In its seed; pesticide, aflatoxin, heavy metal and active substances analysis, microbiological controls have been conducted.

^« In cold press oil; method development, validation and microbiological controls for the analysis of active substances have been conducted.

• in design; which product?, which indication?, what dose?, what dosage form? to be have been calculated.

• in the preformuiation; which active substance/which analysis of the auxiliary substance?, which microbiological controls?, which quality control parameters, which stability studies to be done are considered and a system has been developed accordingly. ^« In stability studies; stability studies have been proven to demonstrate conformity to specified specifications during the anticipated shelf life; 24 months study under 25°C ± 2, 60±5% humidity and 6 months study under 40°C ± 2, 75% ± 5 humidity, have been carried out. Validations and data and package specifications, package specifications, interactions, analysis and control methods related to analytical test methods are determined.

• in preparation of capsule base and internal materials, content determination (oil component analysis), some viscosity and optical appearance control, etc. tests were conducted. • In the production procedure; quality control procedures such as qualitative and quantitative content determination, in-process controls such as optical control and content determinations, microbiological analyzes, optical control, etc. have been applied. Also, HPLC analysis of the active ingredient and product sample was made and fatty acid compositions were calculated. Also, the calibration tables of the active substance are prepared.

The processes described above; are very important details in terms of standardization of herbal products and are detailed in this product. This product has been licensed and approved for pharmacodynamic properties of a Traditional Herbal Medicine product by a health authority such as the Ministry of Health. This product has been approved by a health authority, such as the Ministry of Health, by licensing the KUB (Short Product Information- Prospectus) and T (Usage Instructions) of a Traditional Herbal Medical product. This product has been approved by a health authority such as the Ministry of Health by standardizing and licensing the use of a Traditional Herbal Medicinal product as a form and use. In this sense, the traditional herbal medical product licensed by the Ministry of Health, dosing of which is stated in writing in compliance with the clinical studies has been officialized by obtaining the approval of health authorities and has been presented to the service of world medicine.

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Claims

1. The usage of an herbal formulation comprising pumpkin seed oil, in the production of a medicine used in BPH treatment.

2. A usage as in claim 1 , characterized in that said herbal formulation comprises pumpkin seed oil, dl a-tocopherol, dl a-tocopheryl acetate, glycerin, distilled water, and gelatin which provide the integrity of the content and the capsule formation.

3. A usage according to claim 2, characterized in that it is used by adults at a dose of 960 to 2880 mg/day.

4. A usage according to claim 2, characterized in that it is administrated orally.