FMV Research Projects

DEMOSIMCAN KITS FOR THE TREATMENT OF CANINE DEMODECOSIS

Assoc. Prof. Dr. Narcisa MEDERLE – Project Director (Service Provider)

UNIVERSITY OF AGRICULTURAL SCIENCES AND VETERINARY MEDICINE OF BANAT "KING MIHAI I OF ROMANIA" FROM TIMISOARA – Faculty of Veterinary Medicine

Prof. Dr. Sorin MORARIU

Prof Dr Gheorghe DARABUS

Lecturer Dr Marius ILIE

PhD student Andreea GARTNER

PhD student Adina NEGRESCU

Kumbakisaka Sylviu - General Director (Service Beneficiary)

PRIMOSAL S.R.L. Bucharest

The project DEMOSIMCAN contributes to encouraging the economic agent (CO) S.C. PRIMOSAL S.R.L. to invest in research and development activities for launching innovative products and services on the market based on existing technologies to achieve a high-performance production line for obtaining a kit (consisting of a gel and a shampoo) used in veterinary medicine, intended for treating dry lesions of canine demodicosis caused in the skin of dogs by the mite Demodex spp. and to develop sustainable and durable partnerships between the economic agent and a public research organization (F.S.) - University of Agricultural Sciences and Veterinary Medicine of Banat "King Mihai I of Romania" from Timisoara/ Faculty of Veterinary Medicine.

The idea of the project is to develop ecological products, from natural ingredients with maximum efficiency on animal health, based on plant extracts - as antiparasitic ingredients and collagen - as an ecofriendly ingredient for regenerating already parasitized skin.

The natural biological complex obtained from plant extracts and collagen will be the basic components of the DEMOSIMCAN kit (gel and shampoo) for the treatment of canine demodicosis - a cutaneous parasitosis, caused by mites of the genus Demodex that parasitize in the pilosebaceous follicles, diagnosed in domestic and wild animals, including humans. In canine skin conditions, demodicosis has a high prevalence, with values that can reach in our country a percentage of 32.78%.

Initially, therapeutic protocols applied in canine demodicosis started from classic acaricidal treatment with topical formulations of formamidines and systemic administrations of ivermectins, which continued with spot-on applications (based on moxidectin-imidacloprid) and/or oral administrations with products based on milbemycin. Currently, on the recommendations of specialists regarding new molecules/medications such as: afoxolaner, sarolaner, and fluralaner are used in the treatment of these mites. Thus, over the years, following the successes and failures of researchers in the therapy of demodicosis, we can observe that the treatment of this parasitosis raises a series of problems, such as: the very large number of demodex mites in the skin, their defense mode by locating in hair follicles and sebaceous glands, their feeding mode with sebum and dead follicular cells which protects them from contact and ingestion of lethal amounts of acaricides. On one hand, it is difficult to find a single acaricide that is effective against demodex mites and, at the same time, harmless to the dog, and on the other hand, most topical formulations also have some irritating effect. In the treatment of canine demodicosis, it is often neglected that demodectic skin has a much-modified reactivity compared to healthy skin. In this context, the recommendation of administering natural products with synergistic action due to the complexity of balanced, non-irritating, and non-invasive active ingredients for the skin and organism is evident.

Considering the high prevalence of canine demodicosis, the involvement of intrinsic, extrinsic, and immunosuppressive factors in triggering the disease, but especially, the complex therapeutic approaches, the main objective of this project is the realization, characterization, and testing on parasitized animals of natural products - gel and shampoo, in the form of a kit used in the treatment of canine demodicosis – DEMOSIMCAN consisting of natural extracts, with rapid skin absorption, effective in the remission of demodectic lesions and without irritating effect on parasitized skin.

The first objective of the project aims to select, obtain, and characterize the active principles, key components of the DEMOSIMCAN kit.

Plant mixtures, such as: blackcurrant buds (Ribes nigrum), walnut buds (Juglans regia), cedar shoots (Cedrus libani), rosehip buds (Rosa canina), rye roots (Secale cereale) according to patent application no. A / 00075 from 1.02.2016 - Gel for the treatment of dry lesions of canine demodicosis, of the public research unit (F.S.), have proven to be effective against Demodex mites. The idea of integrating active principles from plants into collagen hydrolysates, to obtain veterinary products significantly influences their quality, as adverse reactions on the dogs' skin will be avoided and implicitly the treatment time will be reduced.

The second objective of the project refers to the formulation, characterization, testing, and selection of active principles of the two components gel and shampoo of the DEMOSIMCAN kit.

Among the semi-solid pharmaceutical forms, currently, there is a particular interest in using hydrogels as supports for preparations intended for cutaneous application. The use of hydrogels is important for applying active principles on membranes or mucous membranes, as the high water content reduces irritability; also, hydrogels present good compliance for animals, characteristics of releasing incorporated active principles and appropriate rheological properties, increased skin tolerance, compatibility with most excipients, ease of application and removal from the skin.

The third objective of the project aims to introduce into production at the economic agent of the DEMOSIMCAN kit, starting from the final formulations in the form of shampoo and gel, which contain active principles from plants and protein hydrolysates of collagen, manufacture of "zero" batch and validation of the manufacturing technology of the DEMOSIMCAN kit to the economic agent and protection of intellectual property rights.

The active biological complex based on natural extracts encapsulated in collagen will be the basic component in the DEMOSIMCAN shampoo and gel and represents an absolute novelty worldwide. These will be characterized from a physico-chemical, biological point of view, but also tested in vivo on animals.

The new vision of the economic agent is to focus especially on the production and commercialization of ecological products used in the treatment of various ectoparasitoses in owned dogs, but also in community dogs. The technological manufacturing line has high-performance equipment for the synthesis and processing of materials that use microwaves and ultrasounds as an energy source, which can operate continuously or discontinuously depending on the estimated production level. The technology to be developed under this funding scheme is based on the use of microwaves and ultrasounds for obtaining biological products, followed by encapsulating active principles from plants in collagen hydrolysate for the manufacture of the two components (shampoo and gel) of the DEMOSIMCAN kit.

The main result of the project will be quantified by the favorable social impact on the quality of life of animals and humans and by the estimated economic impact through: increasing the competitiveness and visibility of the economic agent S.C. PRIMOSAL S.R.L. on the veterinary products retail market, a new field approached in the company's development policy; developing the awareness and sustainability policy of S.C. PRIMOSAL S.R.L. by supporting innovation in the field of ecological technologies and products, valorizing existing and/or insufficiently exploited resources, their sustainable use, which will contribute to increasing the added value of veterinary products and jobs in the private sector; strengthening the practical training of doctoral students by interconnecting the existing expertise in the research unit participating in the project and the needs of the economic agent S.C. PRIMOSAL S.R.L. Other direct advantages compared to existing products and technologies on the market are: achieving a new, ecological product, based on natural extracts, non-existent on the Romanian market with high added value (medical use treatment) and with export potential (increasing quality of life by stimulating economic growth).

In conclusion, the development of an innovative manufacturing technology for a kit consisting of a shampoo and an external use gel with antiparasitic action based on ecological products, namely: plant extracts and collagen is necessary for the market implementation of a new concept correlated with the current trend of market requirements, increasingly stringent restrictions regarding the use of biocidal products with a high-risk degree on animal health and welfare and the environment, and not least, reducing the populations of demodex mites increasingly resistant to classical therapies due to the creation of resistance over time to synthetic compounds.

The major advantages of using mixtures of natural extracts and collagen - biologically compatible compounds with the skin of animals affected by demodectic disease, are the following: lack of side reactions during treatment, reduction of treatment time and rapid healing of the disease which will lead to a reduced transmission rate to healthy individuals, establishing a treatment protocol for demodicosis from the early stage, the affordable price of the proposed solution, namely the DEMOSIMCAN Kit, will represent the major asset of the economic agent for the rapid fulfillment of the proposed indicators.

Impact Report

December, 2018

The main objective of the project was the realization, characterization, and testing on parasitized animals of natural products - gel and shampoo, in the form of a kit used in the treatment of canine demodicosis – DEMOSIMCAN. The patent application no. A / 00075 from 1.02.2016 - Gel for the treatment of dry lesions of canine demodicosis, of the public research unit (F.S.) proved to be effective against Demodex mites. The project beneficiary, PRIMOSAL S.R.L. took over the above-mentioned invention patent application, elaborated together with the Service Provider the second patent application, and carried out all legal procedures for granting the invention patent. Five batches of gel and shampoo products were made, the implementation of the kit on the market began by approaching modern marketing techniques.

The valorization of the project results is achieved through industrialization at the beneficiary of the process, in order to diversify its range of products and services for disinsection, deratization, and disinfection, sanitation, etc. To be able to market the products, procedures for obtaining the market placement authorization were initiated, in applications with a multiplier socio-economic impact. The business turnover development in the first year after completion, corresponding to the estimated production figures, is over 50000 lei, reaching the threshold of 150000 lei in the following years.

Concerns for the continuous innovative development of products intended for veterinary use made based on hydro-glycero-alcoholic plant extracts at PRIMOSAL SRL are continued through participation, in partnership with the UNIVERSITY OF AGRICULTURAL SCIENCES AND VETERINARY MEDICINE OF BANAT "KING MIHAI I OF ROMANIA" FROM TIMISOARA – Faculty of Veterinary Medicine, in the following project calls type Eureka or other competitions that will be launched and that encourage the development of partnerships between SMEs and Universities.

By implementing the DEMOSIMCAN project at PRIMOSAL SRL, a series of objectives specific to the "Innovation Vouchers" Subprogram were achieved, namely:

a) facilitating the formation of collaborations and partnerships between Primosal Srl, beneficiary unit and UNIVERSITY OF AGRICULTURAL SCIENCES AND VETERINARY MEDICINE OF BANAT "KING MIHAI I OF ROMANIA" FROM TIMISOARA – Faculty of Veterinary Medicine, proven also by joint participation in national and international fairs of inventions and innovations, by publishing and participating in scientific events:

• Geneva Inventions and Innovations Fair – gold medal
• Scientific Symposium "Current Issues in Animal Breeding and Pathology", USAMVB Timisoara

http://usab-tm.ro/utilizatori/medicinaveterinara/volumul_L (2)_2017.pdf

• Scientific Symposium "Academic Days" USAMV Iasi

http://www.uaiasi.ro/congres/ "Scientific Works. Veterinary Medicine Series" (ISSN 1454-7406);

b) testing the concepts included in the invention patent, also proven by industrialization at the beneficiary of the process;

c) supporting the innovative SME Primosal in accessing public funds from other sources/programs.

By implementing the DEMOSIMCAN project, 4 jobs were created and a 20% increase in business turnover was achieved. The estimates made by the project proposal were exceeded, which will reflect obtaining positive results in the coming years in this new field approached by the company.

The use of non-polluting technologies for obtaining the shampoo and gel kit used in the treatment of canine demodicosis – DEMOSIMCAN led to reducing the environmental impact, increasing the quality of life and employee safety, improving product quality, and opening the company's activities to the new European trend regarding the restriction of the use of biocidal products in the sanitary-veterinary field.

The development of an innovative manufacturing technology for a kit consisting of a shampoo and an external use gel with antiparasitic action based on ecological products (plant extracts and collagen) implements a new concept correlated with the current trend of market requirements, with increasingly stringent restrictions regarding the use of biocidal products with a high-risk degree on animal health and welfare and the environment, and, not least, with reducing the populations of demodex mites increasingly resistant to classical therapies due to the creation of resistance over time to synthetic compounds.