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1. (WO2018226191) USE OF A HERBAL FORMULATION CONTAINING LINSEED OIL IN THE TREATMENT OF MILD GASTROINTESTINAL (GASTROINTESTINAL SYSTEM) DISORDERS
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USE OF A HERBAL FORMULATION CONTAINING LINSEED OIL IN THE TREATMENT OF MILD GASTROINTESTINAL (GASTROINTESTINAL SYSTEM) DISORDERS

TECHNICAL FIELD

The present invention relates to use of an herbal formulation containing linseed oil (Oleum Lini) in the drug industry in the chemical industry.

In particular, the invention relates to use of an herbal formulation that is prepared with linseed oil being rich in alpha-linolenic acid which is a herbal fatty acid containing Omega 3; that is in the form of a capsule having a antioxidant property, in the treatment of mild gastrointestinal (related to gastrointestinal system) disorders.

STATE OF THE ART

Omega 3 is an essential fatty acid, it is a fatty acid thatshould be taken from outside to maintain the organism's life as other essential fatty acids and that cannot be synthesised in body. This essential fatty acid should be taken by means of nutrition and supplements into body. ALA that is a herbal fatty acid containing Omega 3 taken from outside into organism can be used as a herbal Omega 3 (ALA) source in those, particularly in vegetarians who cannot use fish oil and functions as an adjuvant in regulating some blood lipid (fat) levels, in the treatment of chronic constipation, cardiovascular system disease and mild gastrointestinal disorders.

In the state of art; synthetic substances or chemical agents in certain amounts can be found in the products thatis used as an adjuvant to the treatment of mild gastrointestinal disorders. Use of synthetic and chemicals substances may badly affect the various systems of the body by causing various side effects in the organism.

Further, the products in most of the embodiments are in a liquid form. This complicates the administration of controlled dosing. Therefore, essential dosing cannot be achieved exactly and precisely.

In the literature, one of the patents pertaining to this matter is the application numbered C N103099755. The invention mentions a shower foam prepared with various herbal materials including linseed that is natural and providing vitality and softness to skin.

T he application numbered C N105560646 mentions an herbal mixture comprising nanking cherry, tamarind, banana, dragon's tongue leaf, carageen, R ussian bochniakia plant, J apanese dok roots, Nepal dok roots, radix S crophulariae, radix lithospemi, coffee bean, senna, unripe Inula, orange, pakchoi plantlets, alopecia, senna and peach flowers as well as linseed so as to treat the symptoms such as constipation, irregular bowel movements, hard stool and pellet-like dry stool.

As a result, due to the aforementioned drawbacks and insufficiency of the existing solutions regarding the subject matter, the need for a development pertaining to the treatment of mild gastrointestinal disorders in the related technical field has arisen.

O BJ E CTS O F T HE INV E NTIO N

Main object of the invention is to be able to use linseed oil formulation in the treatment of gastrointestinal (related to gastrointestinal system) disorders.

T he formulation comprises Omega 3, -linolenic acid (ALA, 18:3n-3) and lignans in a high amount T he formulation being rich in linseed oil exhibits laxative effects by initiating intestinal peristaltism related to size increase and extension reflex and exhibits mucosa-protective effect by means of its surface coating effect and thus can be used as an adjuvant in the treatment of mild gastrointestinal disorders. F urther, the formulation being rich in linseed oil helps with increasing bowel movements on adults because of the fibrous structures in linseed. Thus, it can be used as an adjuvant in regulating defecation frequency and continuity, overcoming with constipation and treating mild gastrointestinal disorders.

Another object of the invention is to provide a formulation containing no chemical substances, and being totally natural and herbal. No heat or chemical treatment is carried out even when the linseed oil used in the content of the formulation is obtained. T hus, active substances, nutritional values, vitamin and minerals in the plant are directly infused into the product without losing them.

Another object of the invention is to ensure to minimise the side effects badly affecting the human health by means of the content formed without chemicals. T he side effects affecting

only gastro-entero system such as nausea, vomit, diarrhea resulting from the use of totally natural and herbal products is rarely observed.

F urther object of the invention is to provide ease of use in terms of patient compliance through the fact that the formed formulation is in the form of capsule. F urthermore, it is advantageous in administrating the dosing in said indications by means of the formed capsule form.

D ETAIL E D DE S C RIPTION O F TH E INV E NTIO N

P referred use of an herbal capsule formulation obtained by means of linseed oil so as to achieve the object of the invention is described solely for a better understanding of the subject without generating any restrictive effect.

L ins eed Oil:

T here are oil and lignans being rich in omega-3(ALA) in the linseed. Linseed among the oils obtained through seeds comes into prominence because it has highly -linolenic acid (ALA, 18:3n-3) and lignans. Linseed comprises oil rate of 35-45 percent whose ALA rate is varying between 45-52 percent thereof. ALA is classified as Omega 3 group of fatty acids.

Linseed oil exhibits various pharmacological effects due to ALA in its structure. T he formulation being rich in linseed oil exhibits laxative effects by initiating intestinal peristaltism related to size increase and extension reflex and exhibits mucosa-protective effect by means of its surface coating effect and thus can be used as an adjuvant in the treatment of mild gastrointestinal (related to gastrointestinal system) disorders. F urther, the formulation being rich in linseed oil helps with increasing bowel movements on adults because of the fibrous structures in linseed. T hus, it can be used as an adjuvant in regulating defecation frequency and continuity, overcoming with constipation and treating mild gastrointestinal disorders.

Linseed oil causes serum total cholesterol levels to decrease by 15 percent. Use of linseed oil containing highly ALA decreases serum total cholesterol, LDL (low density lipoprotein) levels on people with hyperlipidemia. F urther, LDL cholesterol levels are decreased on postmenopausal women. T his effect is resulted from S DG (secoisolariciresional diglucoside) composition being precursor of lignans named as enterodiol and enterolactone that is in breasts isolated from linseed, and 33 percent decrease in serum total cholesterol and 73 percent decrease in plaque have been observed. T hese effects of linseed oil clarify the effects inhibiting the development of atherosclerosis and the effects regulating the blood lipid levels.

T he linseed oil may assist in decreasing thrombosis incidence since it has the antithrombotic effects and the effects reducing aggregation of thromboses

Linseed oil exhibits antioxidant effects due to ALA therein. F urthermore, ALA has suppressor effects on interleukin, TN F (Tumor necrosis factor), leukotriene B4 and polymorphonuclear leukocytes. T hese facts can explain the effects of linseed oil that can inhibit the development of inflammation.

It is known that linseed oil can increase calcium absorption. Along with said effect, it has supportive effects on bone health.

T he linseed oil is important for adults who cannot use fish oil, particularly vegetarians within the scope of the fact that it is supportive in terms of herbal Omega 3.

C ontent of caps ule formu lation:

Linseed oil as active substance and dl -tocopherol, dl -tocopheril acetate, glycerin, purified water and gelatin as inactive substances are employed in the formulation, dl -tocopherol and -tocopheril acetate serve as preservative substance. Dl -tocopherol and dl -tocopheril acetate are added into the formulation in the ratio of ppm. Bovine gelatin is used so as to maintain the integrity of content. As an alternative to gelatin, other animal-originated and herbal gelatins can be used.

As is stated on Table 1 ; there exists 42,050 percent of linseed oil, 0,004 percent of dl -tocopherol; 0,021 percent of dl -tocopheril acetate; 10,831 percent of glycerin; 23,547 percent of water; 23,547 percent of gelatin by weight in the content.

Table 1 . Capsule C ontent and Percentage by weight


P roduction method of the caps ule:

P roduction steps of capsule formulation follows as below: linseed oil, one of the raw materials, is subjected to sieving process. After sieving process, if necessary, breaking process is carried out. After carrying out said process and obtained desired size, the linseed oil is sent to cold pressing unit By means of cold pressing method, extraction of oil from raw material is performed. In said method, it is not exceeded over 55 S3. T he oil obtained through cold pressing unit is held in the mixing and settling tanks before filtering process. Thus, possible particles can be easily separated by means of mixing and settling processes.

the extracted oil is fed to the filter unit indoor and at room temperature after mixing and settling tanks. Particles in the oil are filtered in the filter unit if there are. After filtering process, dl -tocopherol and dl -tocopheril acetate as preservative substance are added into the obtained oil. Thus, the mixture of which content is formed, is obtained.

On the other hand, the gelatin is prepared in the gelatin preparing unit so as to maintain the integrity of capsule while carrying out these processes.

After forming the mixture and preparing the gelatin, capsules in desired dosages are prepared by means of sending it to capsule producing unit. S aid capsules are gelatin capsules.

After prepared the capsule, drying process is carried out. Dried capsules are packaged.

Instruction of Us e of Caps ule:

Therapeutic Indications : The capsule is rich in alpha-linolenic acid (ALA) being O mega 3 that is herbal. It is adjuvant to the treatment of patients with chronic constipation. F urther, it is adjuvant to the treatment of cardio-vascular system diseases, regulating some blood lipid (fat) levels and mild gastrointestinal problems. T he capsule can be used as an herbal Omega 3 (ALA) source on those who cannot use fish oil, particularly on vegetarians.

Dos ing and Administration Method:

I Dos ing admin istration frequency and period: As long as doctor recommends otherwise; the capsules are taken orally as 2-4 capsules (1250-2500 mg/day at dose)

per day by adults (aged 18 and older). The capsule can be taken as 1 -2 capsules (625- 1250 mg/day) by children over 12 years of age.

I Ad ministration Method: The capsules should be swallowed along with enough water, preferably on a full stomach without crushing and chewing them in mouth.

Additional Information on S pec ial Populations:

I R enal/liver failure: T he capsules should not be used on the patients with R enal and liver failure because sufficient safety study has not been performed.

I P ediatric population: It is not recommended to use the capsules on the children under 12 years of age because sufficient safety study has not been performed thereon.

i G eriatric population: No sufficient safety study has been performed on elders.

However, it is thought that dose adjustment is not necessary.

C ontraindications:

- Active substance Linseed or any component that the capsule contains should not be used on those who have allergic thereto;

On pregnancy and lactation,

On the patients with liver and renal failure,

On those who have an unspecified rectal bleeding,

- On those who have defecation problems subsequent to laxatives use,

On these patients that are observed to have sudden changes in bowel habits for a period more than two weeks,

On these patients that have bowel paralysis, megacolon and ileus.

S pec ial Warnings and P recautions for Us e

E ach capsule contains 0,161 g of glycerin. It is not expected to appear any side effects resulting from the glycerin at this ratio.

Daily 3 g dosing should not be exceeded on the patient on oral anticoagulation therapy.

T he capsule should be carefully used in the course of the treatment of hormone-related tumors due to its oestrogenic effect.

It should be used on the patients with bowel paralysis and ileus under the doctor control. It is recommended that the capsule use should be maintained by consulting with your doctor if it takes longer than 1 week.

P regnancy and Lactation

I P regnancy period: T he capsule should not be used because no study related to this matter has been performed.

i Lactation period: The capsule should not be used in the course of lactation because its safety in the lactation is not proven.

Undes irable Effects :

i G astrointestinal Diseases: C ommonly meteorism and rarely hypersensitivity reactions similar to anaphylaxis can be observed along with the use of capsule.

F urther, nausea, vomit and diarrhea can be observed, however its frequency is not known.

Apart from these, no undesirable effect is reported.

Overdose:

T here is no reported overdose related to linseed oil. The linseed oil orally taken can be tolerated well. However, it is reported that if the linseed itself is taken orally, abdominal problems such as overdose- related gas and bloating may occur. If any findings occur subsequent to overdose, the treatment should be symptomatic and supportive. There is no specific antidote and elimination enhancement method.

S torage C onditions :

S helf life of the product is determined as 2 years.

S aid capsule of which content and production methods are mentioned above has been licensed by R epublic of T urkey Ministry of Health authorities as "Traditional Herbal Medical P roduct". S aid license bearing the number 2016 856 and the date 02.12.2016 is called as a 625 mg soft capsule by the name "ZAD E VITAL C O RVITAL_. According to the above listed

Indications and Traditional Herbal Medicine P roduct Directive, it is a Traditional Herbal Medicine P roduct LIC E NS E D by R epublic 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 MP (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;

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

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

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

I In the preformulation; which active substance/Which analysis of the auxiliary substance?, which microbiological controls? , which quality control parameters, which stability studies to be done have been considered and a system has been developed accordingly.

I In the stability studies; stability studies have been proven which proves the conformity to specified specifications in the course of 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 have been determined.

I In preparation of capsule base and internal materials, content determination (oil component analysis), some viscosity and optical appearance control, etc. tests have been conducted. i 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 component and product sample was made and fatty acid compositions were calculated. F urther, the calibration tables of the active substance have been prepared.

The 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 SPI (Short Product Information-Prospectus) and UI (Use 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 usage and dosing of a Traditional Herbal Medicinal product. 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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