WO2019004969A9 - Use of a vegetal formulation containing pomegranate seed oil as an assistive agent in reduction of blood lipids known as triglyceride - Google Patents

Abstract

The invention relates to the use of a vegetal formulation in the pharmaceutical industry prepared in capsule form by using pomegranate seed oil rich in essential fatty acids such as punicic acid (Omega 5) as an assistive agent in reduction of blood lipids known as triglyceride and whose formulation comprises pomegranate seed oil, dl a-tocopherol, dl a- tocopheryl acetate, glycerine, purified water and gelatin that procures the integrity of the content and the capsulated formation.

Description

USE OF A VEGETAL FORMULATION CONTAINING POMEGRANATE SEED OIL AS AN ASSISTIVE AGENT IN REDUCTION OF BLOOD LIPIDS KNOWN AS

TRIGLYCERIDE

TECHNICAL FIELD

The present invention relates to the usage of a vegetal formulation consisting of pomegranate (Punica granatum) seed oil in pharmaceutical and chemical industries.

The invention particularly relates to the use of a vegetal formulation prepared in capsule form by using pomegranate seed oil rich in essential fatty acids such as punicic acid (Omega 5) as an assistive agent in reduction of blood lipids known as triglyceride.

PRIOR ART

Essential fatty acids are the type of acids that cannot be synthesized within human body and must be obtained extrinsically in order for an organism keep on living. These essential fatty acids ought to be obtained through certain nutrients or supplements. Essential fatty acids such as Omega 5 (Punicic acid) which is specific to pomegranate seed oil obtained extrinsically and are mainly used as immune system enhancers due to their antioxidant function, as supplements for the preservation of overall health and as agents in reducing blood lipids also known as triglyceride.

In the current state of the art, products used for enhancing the immune system and for lowering blood lipids known as triglyceride, usually contain synthetic or chemical materials in certain amounts. The use of synthetic or chemical materials results in many side effects in the organism and affects bodily systems adversely.

Furthermore, in most of the available embodiments, these products are in liquid form which constitutes certain difficulties for controlled dosing. Therefore, the required dosage cannot be taken in exact and distinct amounts. One of the related patents in the literature is the application bearing number JP2016027023. The said patent application refers to a vegetal and cosmetic formulation that in addition to the pomegranate seed oil, contains many other mixtures which is good for facial and dermal skin sagging when applied externally.

Patent application bearing number DE102009019103 refers to a beverage in which the pomegranate seed oil is dissolved with an emulsifier.

Another patent application bearing number JP2003113028 refers to a component used as a cosmetic and chemically basic hygiene product consisting of pomegranate and other vegetal seed essences.

Abovementioned disadvantages, technical problems and inadequacy of available solutions related to this particular issue necessitated an improvement in the related technical field regarding the use of pomegranate seed oil as an assistive agent in reduction of blood lipids known as triglyceride.

OBJECTS OF THE INVENTION

It is an object of this invention to make sure that the vegetal formulation prepared in capsule form with pomegranate seed oil that is rich in essential fatty acids such as Punicic acid (Omega 5) is used as an assistive agent in reduction of blood lipids known as triglyceride.

Punicic acid (Omega 5) which is the main constituent of this particular formulation, possesses preventive effects on lipid peroxidation both in vitro and in vivo. It shows antioxidative effects by preventing hydroperoxidation. Furthermore, punicic acid has anti- atherogenic effects. Studies have demonstrated the effects of pomegranate seed oil treatment on serum lipid (fat) profiles. These studies have shown that at the end of the 4 week administration period, when the group of pomegranate seed oil was compared to basal values, there has been a significant amount of reduction in both TG (triglyceride) and TG:HDL (High Density Lipoprotein -C). Pomegranate seed oil also plays a regulative role in blood lipid values by reducing the levels of LDL (Low Density Lipoprotein).

Another object of the present invention is to ensure that the prepared formulation has 100% natural and vegetal content without comprising any chemical substances. Even during the extracting process of the pomegranate seed oil used in the content of the formulation, no thermal or chemical treatment is utilized. Thus, active substances, nutritional values, vitamins and mineral within the plant are transmitted straight to the product without any losses.

Another object of the present invention is to minimize the side effects by creating a substance without using any chemical materials that can affect human health adversely.

Another object of the invention is to provide ease of use by capsulating the created formulation in terms of patient compliance and patient interaction. Furthermore, the capsulated form of the formulation constitutes further advantages in obtaining of appropriate dosing in aforementioned indications.

DISCLOSURE OF THE INVENTION

The preferred embodiment of the subject matter formulation obtained by using pomegranate seed oil to achieve invention's objective, is only elaborated for the further clarification of the subject and in a way that does not constitute any restrictive effects.

Pomegranate Seed Oil: The punicic acid (Omega 5) which is the main component of the pomegranate seed oil has preventive effects on lipid peroxidation as in vitro and in vivo. Punicic acid bears antioxidative effects by preventing hydroperoxidation. Furthermore, punicic acid has anti-atherogenic effects. Studies have demonstrated the effects of pomegranate seed oil treatment on serum lipid (fat) profiles. These studies have shown that at the end of the 4 week administration period, when the group of pomegranate seed oil was compared to basal values, there has been a significant amount of reduction in both TG (triglyceride) and TG:HDL (High Density Lipoprotein -C). Pomegranate seed oil also plays a regulative role in blood lipid values by reducing the levels of LDL (Low Density Lipoprotein). Moreover, pomegranate seed oil blocks inflammatory cytokines, increases insulin sensitivity and boosts immune system. Also, it further strengthens the immune system by significantly increasing CD3 (Mature T-Lymphocyte) and total leucocyte values.

Pomegranate seed oil also contains phyto-estrogenic components (17 alpha-estradiol, estrone, estriol and testosterone). Therefore, it can be used as an assisting agent for relieving symptoms (sleep disorders, hot flashes, night sweats etc.) observed during the period of menopause due to the mild estrogenic effects of the said components.

Pomegranate seed oil capsules can also relieve sleep disorders in women observed during the period of menopause. Pomegranate seed oil compounds increase bone density in ovariectomic female rats and also relieves depressive symptoms observed during the period of menopause.

Pomegranate seed oil increases insulin sensitivity in Type-ll diabetic patients.

Administration of pomegranate seed oil in rats reduces weight gain induced with diet, obesity, insulin resistance and the risk rate of type 2 diabetes.

It is known for a fact that in experimental diabetes models created for Zucker rats with streptozosine and alloxane, compounds obtained from various fractions of the pomegranate influence diabetes parameters positively.

Capsulated Formulation Content:

In this particular formulation, pomegranate seed oil is used as the active substance. As for excipients, the formulation comprises dl a-tocopherol, dl a-tocopheryl acetate, glycerine, purified water and gelatin. In this context dl a-tocopherol and dl a-tocopheryl acetate are used as preservative substances. For the said formulation, dl a-tocopherol and dl a- tocopheryl acetate are added on ppm level. For the gelatin added for the integrity of the content, bovine gelatin is preferred. However, as a substitute for the bovine gelatin, animal and vegetal originated other gelatin products can also be utilized.

As it is demonstrated in Table 1 , content percentage by weight is as follows; 48,150% pomegranate seed oil; 0,004% dl a-tocopherol; 0,024% dl a-tocopheryl acetate; 9,690% glycerine; 21 ,065% purified water; 21 ,065% gelatin.

Table 1. Capsule's content and percentage by weight

Glycerine 9,690 80,5

Water 21 ,065 175

Gelatin 21 ,065 175

Capsule's Production Method:

Production steps of the capsule's formulation can be described as below; pomegranate seed which is one of the raw materials is put to a sifting process. Pursuant to the sifting, crushing step is carried out if necessary. After pomegranate seeds are put through these processes and desired size is obtained, seeds are sent to a cold isostatic pressing unit. This unit carries out the oil extraction process from the raw materials using the cold pressing method. While the said method is being put to practice, the temperature must not exceed 55°C. Extracted oil are preserved in mixing and settling tanks prior to the filtration process. Preservation of extracted oil in mixing and settling tanks facilitates the separation of occurring particles. Following its preservation in mixing and settling tanks, extracted oil is sent to filtering unit which is held indoors and room temperature. In the filtering unit, if any, particles within the content of the oil are filtered. Following the filtering stage, dl a-tocopherol and dl a-tocopheryl acetate are added to the acquired oil as preservative substances. Thus, the mixture composing the content is obtained.

Meanwhile these production steps are carried out, in the gelatin preparation unit the gelatin that is used for the capsule integrity is prepared.

Subsequent to the creation of the mixture and the preparation of the gelatin, both the mixture and the gelatin are sent to the capsule production unit and capsules with desired dosage are prepared. This said capsule is namely soft gelatin capsule. Following the preparation of capsules, drying process is carried out and dried capsules are packed.

Capsule's Package Insert: Therapeutic Indications

Capsule is used as an immune system enhancer for the protection of health due to its antioxidant functions and also used collaterally in reduction of blood lipids also known as triglyceride. Dosing and Method of Administration

• Dosing administration interval and period: Unless advised otherwise by a physician, capsules can be taken by adults up to 1 to 2 capsule(s) (400-800 mg/day) per day.

• Method of Administration:

Capsules should be swallowed preferably on a full stomach with sufficient water and without being crushed or chewed.

Supplementary Information Related To Specific Populations:

• Renal/liver failure

Since safety studies conducted in kidney and liver patients aren't adequate, capsules should not be used in these particular patient groups.

• Pediatric Population

Since safety studies conducted in this particular population aren't adequate, capsules should not be used in patients under 12 years of age.

• Geriatric Population

There are no studies carried out in geriatric population. However, it is thought that a dose adjustment is unnecessary.

Contraindications

Capsules should not be used by

- persons who might develop allergic reactions to the active substance or any other component of the capsules' content

- women who are in pregnancy and lactation period

- patients with liver and kidney failure

Special Precautions and Warnings For Use Capsule contains glycerine, however, this does not necessitate any warnings because of its amount.

It is advised that use of the capsule longer than 2 months is to be continued in consultation with a physician.

Pregnancy and Lactation

• General Advice

Pregnancy category: C

• Women with childbearinq potential/Birth control

Capsule should not be used since there are no studies related to this subject.

• Pregnancy Period

There are no studies related to the use of pomegranate (Punica granatum) seed oil during the pregnancy period, therefore, use of the capsule is not advised.

• Lactation Period

There are no studies conducted for this particular patient group, therefore, use of the capsule is not advised.

Undesirable Effects

Even though the incidence is unclear in the use of the capsule, gastrointestinal side effects including nausea, vomiting and diarrhea could be observed. Apart from the abovementioned effects, no other undesirable effects have been reported.

Overdose

No overdose incidents have been reported to date with regard to pomegranate (Punica granatum) seed oil. In case of an overdose, the treatment must be discontinued and a physician should be consulted.

Storage Conditions

The shelf life of the product is determined to be 2 years. The capsule whose content and production method is the subject matter above, has been licensed by the authority of the Ministry of Health of the Republic of Turkey as "Conventional Herbal Medicinal Product". The said license bears the date of 21.1 1 .2016 and the sequence number of 2016/829 and goes under the name of ZADE VITAL PUMI NI N 400 mg soft capsule. The capsule is a LICENSED Conventional Herbal Medicinal Product by the Ministry of Health of the Republic of Turkey in accordance with the abovementioned indications and the Regulation for Conventional Herbal Medicinal Products. There are a number of licensed products containing a large number of synthetic chemicals in the market for the stated indications. However, in this particular field there are no conventional herbal medicinal products licensed for these indications by the health authorities.

While in the majority of the available embodiments the production is carried out under bad hygiene conditions, however, related formulation is manufactured in accordance with GMP (Good Manufacturing Practises) norms required by the Ministry of Health from a pharmaceutical factory.

As is known, it is rather difficult to maintain standardization in vegetal products.

Regarding the corresponding formulation;

• Microbiological controls and analyses of pesticides, aflatoxins, heavy metal and active substances of the seeds have been carried out.

• Microbiological controls, validation and method development for the analysis of active substances have been conducted in the cold pressed oil.

• Products, indications, dosing and form of dosing have been calculated in the design.

• Analyses of active substances/excipients, microbiological controls, quality control parameters and stability studies to be carried out were considered and the system was developed accordingly in the preformulation.

• Conformity to determined specifications during the predicted shelf life has been proven by stability studies. A 24-month study has been carried out in 25°C±2, % 60 ±5 humidity and another 6-month study has been conducted in 40°C±2, % 75 ±5 humidity throughout the stability studies. Validations and data related to analytic testing methods, packaging specifications, interactions, methods for analyses and controls have been determined.

• During the preparation of intra-materials and capsule basis certain tests such as content designation (analysis of oil components), viscosity and optical prospect etc. have been carried out.

• Throughout the production stage, quality control procedures such as content designations, microbiological analyses and optical controls, also in-process controls such as optical control, qualitative and quantitative content designation have been carried out. Moreover, HPLC analyses of the sample product and active substance were conducted and fatty acid compositions were calculated. Furthermore, calibration tables of the active substance were drawn.

Abovementioned processes are crucial in terms of standardization of vegetal products and these processes have been carried out at full length. The said product has obtained certification from a health authority such as the Ministry of Health through licensing of the pharmacodynamic characteristics of a Conventional Herbal Medicinal Product. Again, this particular product has obtained certification from a health authority such as the Ministry of Health by having its summary of product characteristics (spc) and its Package Insert (PI) licensed. The said product obtained certification from a health authority such as the Ministry of Health through standardizing the method of administration and dosing of a Conventional Herbal Medicinal Product. In this context, dosing of a Ministry of Health licensed conventional herbal medicinal product was put in writing pertinent to the clinical trials, was officialized through the approval of health authorities and was put at the disposal of the global medicine.

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Claims

1. The invention is the use of a vegetal formulation comprising pomegranate seed oil as an assistive agent in reduction of blood lipids known as triglyceride in manufacturing of a medication.

2. The use according to claim 1 , characterized in that, the said vegetal formulation comprises pomegranate seed oil, dl a-tocopherol, dl a-tocopheryl acetate, glycerine, purified water and gelatin that procures the integrity of the content and the capsulated formation.

3. The use according to claim 2, characterized in that it is used in adults in the dosing of 400- 800 mg/day.

4 . The use according to claim 2, characterized in that it is administered through the oral route.