2015 Best Biotechnology Product Award Winner

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Application regarding the product DIAVIT

  • A brief, non-technical description of the product including the following information:
         * Which problems can the product help to solve?
         * How does the product work?
         * Details of product novelty
         * Details of product applications
         * Advantages over similar previous products (if not completely novel)
  • A technical dossier
  • Information about the marketing of the product

     * Is it already on the market? 
     * If so, in which countries?
     * Does the submitting company have data on consumers' acceptance? 

1. Non-technical description of the product

The product DIAVIT is a whole natural concentrate of Vaccinium myrthillus L. and Hippophae rhamnoides L. fruits of spontaneous flora obtained by genuine processing, protecting the main active components and by adding glucose, starch and lactose. The product is rich in natural principles, such as: antocyanosides, vitamins, mineral salts, phytoncides, tannins, vegetal acids, pectines.
The product is used in the treatment of diabetes.

As active ingredients, DIAVIT contains: flavonoides, anthocyans and anthocyanids, saccharides, pectic substances, tannins, vitamins, flavones derivates, organic acids, mineral salts, 3 glucosides, 3 galctosides, neo-myrtilline, hydro-quinone due to the increased blueberry content.
The hypoglycaemiant action of DIAVIT is determined by the glycosides of the delphinol, myrtilline and the neo-myrtilline contained by the natural fruits concentrate.

Pharmacologically, anthocyanosides are thought to decrease vascular permeability and improve microcirculation. It remakes the vascular resistance and it is tonic to the venous system. Flavonoids, due to their P-vitamin potential, trophyc and anti-atherogenic action protect blood vessel walls. Due to its diuretic and slightly coronary dilatation action it promotes cardiovascular adjustment and regulation of blood pressure. It has an active effect on the regeneration of retinal purple, which increase the visual acuity. Delphinol glycosides, myrtilin and neomyrtilin have a hipoglycaemical effect at the level of beta cells in Langerhans islets, is correlated with glycaemia depression.

Hypoglycemic effect of DIAVIT is due to a slight hypergenesis at the level of beta cells (the regenerative effect on distroyed pancreatic cells was observed in studies on animals), it contains so called "vegetal insulin" (myrtilene and neomyrtilene). It can be associated with insulin and insulin doses can be gradually reduced due to the hypoglycaemic effect of the product (fact observed in type 2 diabetic patients). The regenerative effect on beta cells appears after 3-5 months of treatment with DIAVIT. On long term, antocyanids have a benefic effect on the treatment of diabetic retinopathy and angiopathy.

The product also contains carotenoids which are recognized for their antioxidant capacity. In fact, carotenoids are considered the most potent biological quenchers of singlet oxygen. Due to its component DIAVIT has also an antioxidant activity,

DIAVIT is trademarked being registered at Romanian State Office for Inventions and Trademarks (Oficiul de Stat pentru Invenţii şi Mărci, OSIM Romania) in 2010, no. M 2010 02164 / 29.03.2010, by prof. Morar Roman and Assoc. Prof. Dana Liana Pusta, mark number 110204.
DIAVIT is a phyto-terapeutical product, it has no toxic risk for the liver and kidney, no cummulative effect, is very well tolerated by the organism. No side effects were reported. The effect in the diabetes treatment is recorded after 2-3 months of treatment and it has a regerative action of the β Langerhans cells of the pancretic islets, so enables the patient to reduce the dosis of insulin or drugs used in the current treatment of diabetes. Progresivelly the treatment can be made only with DIAVIT which has a protective action of the pancreas.

2. Technical dossier

In this part of the presentation we will designate DIAVIT as the product/our product.
The effect of DIAVIT concerning the lowering of glucose level in the blood has been checked in most of the species, during the time in many experiments on healthy animals, in experimental diabetes in rats and finally in humans, after it was aproved to be used in human medicine. Some of the experiments were previously made with our, let we name it „starter product” Eridiarom®, which contained only our original blueberries concentrate. After these preliminary studies we improved the action of the blueberries with the seabuckthorn.

In some researches we proved the hypoglicemic effect obtained in healthy piglets, lambs and rabbits in which were administered different quantities of the product. The glycemia decreases in piglets after 10 days of orally administration from 77.29±2.28 mg % to 57.89±6.98 mg%, in lambs after 5 days of oral administration from 46.2 mg% to 38.2 mg% and in rabbits from 87.0±9.7 mg% to 56.25±5.28 mg%.
We conduct another important research with the purpose to study the protective effect of our original phytotherapeutical product in subclinical experimental diabetes induced with Streptozotocin in three groups (n=10) of male rats, belonging to Wistar race with an average weight of 180±15.82 g.
In the first group the administration of the product in the food (1.5g/head/day) started 7 days before the induction of the diabetes with Streptozotocin(n=10). In the second group (n=10) the product was intragastrical administered, two hours before the Streptozotocin.
In all three groups of male rats the subclinical diabet was induced, administering 4mg/100 g body weight Streptozotocin i.p (n=30).
It was studied the glucose concentration dynamic in the blood serum from two to two weeks, using Glu-Cinet Test God/Dod enzymatic method.
At the end of the experiment the pancreas was sectioned at 5 mm and stained Trichrom-Goldner.

Before the inducing of the diabetes, the mean values of the glycaemia were 102.63±6.63 mg % in the first group; 100,9±4.23 mg % in the second group and 102.37±4.53 mg % in the third group.
After the Streptozotocin administration the mean value of glycaemia increased to 346.25±10.23 mg % in the first group; to 345.0±12.67mg % in the second group and to 346.10±14.20 mg% to the third group.
After two months of treatment with the product in the first group the mean value of the glycaemia was 120,4±3.57 mg %, in the second group was 135.30±5.92 mg % and in the third (without treatment) was 150,9±7.28 mg %.
After three months, the mean values of the glycaemia were: 100,3±3.57 mg %  in the first group, 110±6.32 mg % in the second and 124,5±5.21 mg % in the third group.

The results proved that our product protect the b cells from Langerhans islets against the toxic action of Streptozotocin.
Studies on rats showed histologically that the product administred orally for at least 2 months can regenerate Langerhans islet cells and exocrin pancreatic tissue, stimulating development of cell organits that take part at the insulin synthesis process.
The histological exam emphasized that after the diabet inducing the Langerhans Islets remain with only few b cells. After two, respectively three months of treatment with the product the Langerhans Islets are recovering.

The product administered oraly 1,5 g/head/day in food for a long time (2-3 months) normalizes the glycaemia in the rats with subclinical diabet induced with Streptozotocin, and the histological exam confirms the recovery of the b cells. After two weeks of ceasing the product administration, the glycaemia level was maintained in normal limits.

Our product proved to protect β cells in Langerhans islets against the effect of Steptozotocin.
The blueberry concentrate has a hypoglycemic effect due to a slight hypergenesis at the level of beta cells (the regenerative effect on distroyed pancreatic cells was observed in studies on animals), it contains so called "vegetal insulin" (myrtilene and neomyrtilene). It can be associated with insulin and insulin doses can be gradually reduced due to the hypoglycaemic effect of the product (fact observed in type 2 diabetic patients). On long term, antocyanids have a benefic effect on the treatment of diabetic retinopathy and angiopathy.

The cummulative data on 20 persons (10 male and 10 women) with type II diabetes, treated with the product in hospital, under medical surveillance, show that the initially mean value of glycemia of 190.13±8.24 mg% decreases after one months to 151.5±5.25 mg%, after 2 months to 130.6±4.36 mg%, after 3 months to 114.1±3.25 mg% and after 4 months to 84±3.12 mg% and the general state of the persons is improved.

Clinical observations made by Donca, on 86 patients with chronical digestive affections (of different etiologies). The group consisted of 46 female patients and 40 male patients, with ages between 24 and 83 years and the average body weight of the patients was 82±10.34 kg. The treatment shows a positive influence on the values of the glycemia and upon the circulatory system (improvement or stop of  diabetic retinopathy, diabetic angiopathy and blood pressure values), beside the antidiarrheic effect and the already known effect of intestinally motility regulation. It can be seen that after the first 30 days of administration of the product the average value of glycemia was 151±14.36 mg%, after 60 days at 128±9.23  mg%, after 90 days at 114±5.63  mg%, and after 120 days at 94±3.78 mg%.

Also studies conducted by other researchers Crăciun, Nemes-Nagy, over the last years on patients revealed that oxidative stress plays a major role in the etiology of diabetes and in the complications produced by the above mentioned disorder. Oxidative stress is defined as an imbalance between the generation of reactive oxygen species (ROS) and antioxidant defense mechanisms. Free radicals inhibit insulin secretion interfering at different levels of the stimulation-secretion cycle. There is growing evidence that ROS are involved in autoimmune destruction of beta-cells in type 1 diabetes mellitus. ROS act as second messengers of interleukins. Hypotheses explaining the development of diabetic complications due to hyperglycemia involve the imbalance between pro-oxidants and antioxidants.

In healthy individuals, oxidative tissue damage is prevented by a defense mechanism, which includes enzymatic and non-enzymatic antioxidants. Superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase are three primary enzymes involved in direct elimination of active oxygen species (superoxide radical, hydroxyl radical, and hydrogen peroxide).

It was investigated the relationship between the glycated hemoglobin, C peptide and two antioxidant enzymes. Thirty type 1 diabetic children were treated with the product- DIAVIT for two months. The results proved that after two months of administering the concentrate to diabetic children, the erythrocyte superoxide dismutase activity was significantly higher (p<0.05). Levels of glycated hemoglobin were significantly lower (p<0.05). The activity of whole blood glutathione peroxidase was moderately increased, but the difference was not statistically significant. C peptide concentration was significantly higher after treatment with the extract (p<0.05).

Due to their richness in natural components the blueberries and seabuckthorne were used to the production of many phytotherapeutical products. It was proved that they can be used with very good results in the prevention and treatment of neo-natal diarrhea in animals and children, in the treatment of other types of diarrhea in humans and animals and also in the treatment of type I diabetes, determining the recovery of beta-cells, after a treatment of at least two months.

Szőcs-Molnár Terézia, studied the Influence of dietary supplement DIAVIT on metabolic balance in type 1 diabetic children. A simple-blind, placebo controlled study was carried out on a group of 8-18 years old diabetic children. Amongst other parameters they were followed the evolution of glycated haemoglobine, insulin doses, glycaemic profile, urine analysis.

The results proved that the mean values of glycated haemoglobine presented a significant decrease under the treatment with Diavit® (p<0,05), glycaemic profile shows a significant improvement (p<0.005), most of the patients (63%) reduced their insulin doses due to frequent hypoglicaemia. Glucosuria diminished under the treatment with Diavit®, the difference is at the limit of significancy (p=0,0609), and the slight decrease in cetonuria is not statistically significant (p=0,2629). The patients did not present any unpleasent side-effects during the study. Treatment with placebo did not cause significant differences in these parameters.

The main conclusions of the study were that the treatment with dietary supplement DIAVIT associated with insulin, has significant benefic effects on metabolic balance in the studied patients, without presenting any side-effects, so it deserves to be part of the phytotherapeutical arsenal to be used in diabetes mellitus.

The researches made by Zah and col., regarding the dynamics of blood biochemical indexes obtained in the treatment of experimental diabetes in rats with Eridiarom® and DIAVIT , were carried out on 63 male rats, aged of 2 months, Wistar breed, divided into five groups, one healthy and in the other four experimental diabetes was induced with Streptozotocin. Two groups were treated orally with Eridiarom® and DIAVIT phyto-therapeutic products and one group with Siofor. Monthly samples were collected for monitoring blood biochemical parameters (for 7 months). It was noticed that after the first month, serum calcium begins to reach the normal limit, and after two months so do the magnesium, glucose, serum urea and creatinine. In the groups treated with Eridiarom® and DIAVIT, the glucose level in blood decreases progressively after 2-3 months, reaching the normal values after 7 months. After the first month, the average urea values in blood increased significantly in the control group (with the induced diabetes) and untreated group, as well as in the group treated with Siofor. Lower values are found in groups treated with Eridiarom® and DIAVIT. After 3 months untill the end of research, urea remains low in the groups treated with Eridiarom® and DIAVIT.

It is important to remark that after 5-7 months of treatment with the phytotherapeutical concentrates containing blueberries and seabuckthorn, the above mentioned blood parameters values return to normal within the treated groups, but they remain significanly changed in the control group, in which the diabetes was induced.

Another important topic studied by us was the treatment of the eye lesions in diabetes with our original phytotherapeutical product. In this research we studied the possibility to ameliorate the retinopathy and the diabetic cataract which has a high incidence.

The researches were made on Wistar male rats, with the average bodily weight of 150 g, in which the diabetes was induced by i.p. injection of 4 mg/100 g bodily weight Streptozotocin. After 3 days, there were formed 2 groups of 6 animals each, and another group of 6 healthy animals, not injected (the healthy control group). The groups were marked as follows: Group 1 representing the healthy group; Group 2 in which the diabetes was induced with Streptozotocin (group with diabetes) and Group 3 in which the diabetes was induced with Streptozotocin and after that it was treated with DIAVITÒ3 g/day (3 tablets/day) for 90 days.

The observations were made for a period of 90 days and than the histopathologic exam of the eyes was made.

The lesions in diabetes are given by the capillaries that loose their elasticity, permeability and, very often forming thrombus. In eye, because the organ is closed in a less elastic membrane (sclera) the edema determine the dilacerations of the retina and ciliary processes “crushing” the cells that loose their functionality. As a consequence the retina “starts growing” being wrong considered as “proliferative retinopathy”.

DIAVIT acts on the capillaries, improving their elasticity, they becoming able to “drain” the intercellular plasma, reducing the edema and recovering the retina.

The lesions in the diabetic eye, localized in retina, lens or ciliary processes are characterized by diffuse edema and in lens by infiltrations with neutrophils.

The thermo-cauterization of the fragile capillaries, which is classically used as a treatment of the disorder, leads to the aggravation of the edema, makes more difficult the retina’s irigation and thus the amelioration of the lesions becomes difficult.

The replacement of the lens infiltrated with neutrophils does not solve the problem, because it means to section the capillaries and the edema will aggravate and the new lens is superposed on a retina with edema, less receptive.

In our experimental researches, we demonstrate that the infiltrative lesions disappear after 3 months of treatment with DIAVIT and the lens becomes functional again.

Studying the lesions in the diabetic eye, we consider that, in fact, the lesions are vasculopathies.

Another study regarding the effect of the product was focused on the histopathological changes in the rats’ kidney in experimental diabets induced with Streptozotocin.

The researches were made on 35 rats divided into 5 groups as follows: group 1- healthy control group, the rest of the following groups were treated with Streptozotocin for the diabetes induction and divided as follows: group 2 – ill and untreated group (control ill group), group 3 – treated with Siofor (oral antidiabetic) ½ tablet per day, equivalent with 12 mg/kg bodily weight, group 4 – treated with Eridiarom®  2.7g/day/head, and group 5 – treated with DIAVIT 3/day/head. All the groups were maintained and feed in standard conditions during all the experimental period.

After 3, 5 and 7 months by each group were slaughtered 2 rats. The samples were fixed in formalin and processed by paraffin embedded, sectioned and Hematoxylin - Eosin stained and examined under the light microscope.

The histopathological results obtained after 7 months are the followings:
The group 1 – healthy control group presents the glomerulus formed by capillary vascular balls with many loops, and the Bowman capsule is visible.
In the group 2 – ill and untreated, is noticed the atrophy of the vascular ball with mesangial hyperplasia and an exaggerate dilatation of the Bowman space with the capsule oedema and sclerosis.

In the group treated with Eridiarom®  (for 7 months) it is noticed that the renal glomerules are visible, with Bowman capsule without fibro sclerosis, the vascular ball and the mesangial cells are both functional, which delimitate the permeable and functional glomerulus capillary.

In the group treated with DIAVIT (for 7 months) it was noticed the renal glomerulus’s well identified, the vascular ball with functional cells without fibrosis or sclerosis processes, in some arias we noticed the hiperfunctional renal glomerulus with the atrophy of the mesangial cells.
Concluding, we can state that all renal lesions in diabetes mellitus are represented by vasculopathies.

After the treatment with Eridiarom® and Diavit® it was noticed that they have a vascular protective action and also stimulate the glomerulus capillary circulation.

Due to their richness in natural components the blueberries and seabuckthorn were used to the production of many phytotherapeutical products. It was proved that they can be used with very good results in the prevention and treatment of neo-natal diarrhea in animals and children, in the treatment of other types of diarrhea in humans and animals and also in the treatment of type I diabetes, determining the recovery of beta-cells, after a treatment of at least two months.

3. Information about the marketing of the product

The product DIAVIT is only on the Romanian market.
Being a family business we can produce only dozens of cans per day (60 pills of 1g/can) so our market could not be extended abroad.
There were not made any special studies regarding the consumers market because at present the demand of the consumers is much higher compared to our manufacturing capacity. Our original manufacturing process is pretty elaborated and it takes also some time consuming stages.