WO2018222163A2

WO2018222163A2 - Use of an herbal formula containing pumpkin seed oil in the treatment of overactive bladder and urinary incontinence of the lower urinary system symptoms

Info

Publication number: WO2018222163A2
Application number: PCT/TR2018/050067
Authority: WO
Inventors: Mevlüt Büyükhelvacigi̇l
Original assignee: Helvacizade Gida İlaç Ki̇mya Sanayi̇ Ve Ti̇caret Anoni̇m Şi̇rketi̇
Priority date: 2017-02-28
Filing date: 2018-02-26
Publication date: 2018-12-06
Also published as: TR201703084A2; WO2018222163A3; WO2018222163A9

Abstract

In the pharmaceutical industry, the present invention is related to the use of an herbal formulation as a soft capsule, prepared with pumpkin seed oil rich in terms of essential fatty acids content, having antioxidant properties in the treatment of lower urinary tract symptoms associated with overactive bladder and urinary incontinence. Said herbal formulation comprises pumpkin seed oil, dl α-tocopherol, dl α-tocopheryl acetate, glycerin, distilled water, and gelatin which provides the integrity of the contents and capsule formation.

Description

USE OF AN HERBAL FORMULA CONTAINING PUMPKIN SEED OIL IN THE TREATMENT OF OVERACTIVE BLADDER AND URINARY INCONTINENCE OF THE

LOWER URINARY SYSTE SYMPTOMS

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 treatment of lower urinary tract symptoms associated with overactive bladder and urinary incontinence by an herbal formulation in a soft capsule form which has an antioxidant feature and prepared by pumpkin seed oil which is rich in terms of essential fatty acid content

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 fatly acids should be taken into the body via nutrients or by certain supplements. Essential fatty acids taken from the outside into the organism serve as assistants to the treatment of lower urinary tract symptoms associated with overactive bladder and urinary incontinence. In the present technique; within the products that are used as assistants to treat lower urinary tract symptoms associated with overactive bladder and urinary incontinence, 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 badly many sxystems of the body.

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. CN105981810. The present invention mentions, in addition to pumpkin seed extract, many herbal products, blood pressure regulator obtained from water and highly milk mixture, kidney and spleen refresher, yeast yoghurt helping with constipation treatment and retarding aging.

Application no.C I 02908544 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 the treatment of lower urinary tract symptoms associated with overactive bladder and urinary incontinence has been required.

O BJ E CT O F T H E INV E NTIO N

T he object of the present invention is to provide an herbal formulation for use in the treatment of lower urinary tract symptoms associated with overactive bladder and urinary incontinence.

Formulation is rich in terms of pumpkin seeds; phytosterois, tocopherols and essential fatty acids (mostly linoleic and oleic acid) and the active components within the pumpkin seeds are W-sterols (avenasterol and spinasterol) and 5-sterols (sitosterol, stigmasteroi).

T here are many effects of pumpkin seed oil on incontinence (urinary incontinence), one of the problems seen in postmenopausal women and at a later age in men. T he substances found in the content of pumpkin seed oil have anabolic effects on the pelvic muscles. Depending on this effect, the contraction of the pelvic muscles is strengthened. Also, when the bladder is full, nitric oxide is needed so that the muscles can relax and the urination function can be performed. When nitric oxide synthesis is inhibited, bladder activity increases and bladder volume decreases. When the bladder is filled with nitric oxide, pumpkin seed oil relaxes the bladder muscles and prevents incontinence. Due to these dual effects on pelvic muscles and nitric oxide, pumpkin seed oil reduces incontinence complaints.

P umpkin seed oil is inhibiting 5- reductase enzyme. In this way, it can be used as an adjunct to the treatment of prostate gland-related diseases by preventing conversion of testosterone into dihydrotestosterone (DHT). P umpkin seed oil can also be used as an adjunct to the 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 chemica l treatment is a pplied. S o; the active substa nces, nutritional values and minera ls within the plant, pass directly to the product without getting lost.

Another object of this invention is to provide a reduction of the side effects that affect huma n hea lth to a minimum, thanks to the content created without the chemica ls. S ide effects that affect only the gastrointestinal system such as nausea, vomiting and diarrhea, a re 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, tha nks to created ca psule form, it is adva ntageous to obtain dosing in said indications.

D E TAIL E D D E S C R IPTIO N O F T H E INV E NTIO N

T he preferred use of an herba l ca psule formulation obta ined using pumpkin seed oil to achieve the object of this invention is disclosed only for the sa ke of better understanding of the present invention a nd without any limiting effect.

P umpkin seed oil has been used for centuries as a n herba l medical product. P umpkin oil shows many different pharmacological effects due to the wide variety of substances \ the composition and the different therapeutic activities of each.

P umpkin 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 V7- sterois (avenasterol a nd spinasterol) and V5-sterols (sitosterol, stigmasterol). T here are many effects of pumpkin seed oil on incontinence (urinary incontinence), one of the problems seen in postmenopa usal women and at a later age in men. T he substances found in the content of pumpkin seed oil have anabolic effects on the pelvic muscles. Depending on this effect, the contraction of the pelvic muscles is strengthened. Also, when the bladder is full, nitric oxide is needed so that the muscles can relax and the urination function can be performed. W hen nitric oxide synthesis is inhibited, bladder activity increases a nd bladder volume decreases. W hen the bladder is filled with nitric oxide, pumpkin seed oil relaxes the bladder muscles and prevents incontinence. Due to these dua l effects on pelvic muscles a nd nitric oxide, pumpkin seed oil reduces incontinence complaints. P umpkin seed oil is inhibiting 5- reductase enzyme, in this way, it can be used as an adjunct to the treatment of prostate gland-related diseases by preventing conversion of testosterone into ciihydrotestosterone (DHT). P umpkin seed oil can also be used as an adjunct to the treatment of urinary tract infections, especially cystitis.

P umpkin 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 S chistosomiasis, 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.

C aps ule formulation content: In the formulation, pumpkin seed oil is used as the active substance and di -tocopherol, di -tocopheryi acetate, glycerin, purified water and gelatin are used as adjuvant substances, dl -tocopherol and di -tocopheryi acetate are used as protecting agents. In said formulation, di -tocopherol, dl -tocopheryi 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% di -tocopherol; 0.0213% dl - tocopheryi acetate; 10,723% glycerin; 23,312% water; 23,312% gelatin by weight, are used.

Table 1. C ontent of the caps ule and percentages by weight

C aps ule prod uction method:

T he producing 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. T he pumpkin seed is sent to the cold press unit after said processes and after the desired size is obtained. T he process of oil extraction from the raw material is carried out by the cold press method. In said method, 55¾ should not be exceeded. T he oil from the cold press unit is kept in mixing and resting tanks prior to filtration. T hus, it is easy to separate the possible particles by mixing and resting processes.

E xtracted 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 -tocopherol as a preservative and dl -tocopheryl acetate as a preservative are added to the obtained oil. T hus, 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 conveying to the capsule production unit. S aid capsule is soft gelatin capsule.

After the capsule is prepared, drying process is carried out. Dried capsules are packed. C aps ule Usage Instruction: T herapeutic Indications

T he capsule is rich in terms of essential (basic) fatly acids content. It is used as an adjuvant in treating lower urinary tract symptoms associated with overactive bladder and urinary incontinence.

Dosage and Administration Method δ 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. θ Method of administration: Capsules should be swallowed with sufficient water without crushing or chewing in mouth, preferably in full stomach.

Additional information on S pec ial Populations:

S Kidney/liver failure: It should not be used in these patient groups as there is no adequate safety study carried out on kidney and liver patients. θ P ediatric population: T he capsule should be used on children under the age of 18 and adolescents under physician control.

SG eriatric population: There are no studies conducted in the elders.

C ontraindications

It should not be used;

-on those having an allergy to the active substance or any component of the capsule,

- During pregnancy and breastfeeding,

- On patients with liver and kidney failure.

3 g daily dose of capsules should not be exceeded on the patients using oral anticoagulant drug.

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

C onsult 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.

P regnancy and Lactation δ G eneral Recommendation: It should not be used on women with childbearing potential because there is no study related to contraception. δ Pregnancy period: Clinical data on exposure to pumpkin seed oil in pregnancies are not available. Studies in animals are inadequate with regard to effects on pregnancy and/or embryonal/fetal development and/or natal and/or postnatal developments. The potential risk to people is unknown. There is no adequate information on its usage along with oral contraceptive drugs. Since its safety is not shown in pregnancy, it is not recommended to use the capsule during pregnancy. θ Lactation period: Since its safety in lactation is not shown, it is not recommended to use the capsule in lactation.

Undesirable Effects δ 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 and no effects related to overdose are expected. However, if any signs appear subsequent to taking overdose, 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 determined as 2 years. Said capsule of which content and production methods are mentioned above has been licensed by Republic of Turkey Ministry of Health authorities as "Traditional Herbal Medical Product". Said license bearing the number 2016/825 and the dated 21.11.2016 is called as a 320 mg soft capsule by the name ADE VITAL CUCURMIN_. 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 having such an indication licensed by health authorities in this area. in the majority of current applications; while production in poor hygiene conditions is matter of concern, the related formulation is produced under G !VSP (G ood Manufacturing P ractices) 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;

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

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

6 In design; which product? , which indication? , what dose? , what dosage form? have been calculated.

β In the preformulation; which active substance.A/vbich 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.

Θ In stability studies; stability studies have been proven to demonstrate conformity to specified specifications during the anticipated shelf life; 24 months study under 25S3 e 2, 60e5% humidity and 6 months study under 40S3 e 2, 75% e 5 humidity, have been carried out. Validations and data pertaining to analytical test methods and package specifications, interactions, analysis and control methods related to analytical test methods are determined.

6 In preparation of capsule base and internal materials, content determination (oil component analysis), some viscosity and optical appearance control, etc. tests were conducted.

6 In the production procedure; qualitative and quantitative content determination, in-process controls and content determination such as optical control, microbiological analyzes, quality control procedures such as such optical control have been applied. Also, H P LC analysis of the active ingredient and product sample was made and fatly acid compositions were calculated. F urther, the calibration tables of the active substance are prepared.

T he processes described above are very important details in terms of standardization of herbal products and are carried out in detail 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 KU B (S hort P roduct Information- P rospectus) and KT (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 officialised by obtaining the approval of health authorities and presented to the service of world medicine.

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Claims

C LAIMS

1 . it is the usage of a herbal formulation comprising pumpkin seed oil in the production of a medicine for treating lower urinary tract symptoms associated with overactive bladder and urinary incontinence.

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

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

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