Intramammary formulations for mastitis

Abstract

The present invention relates to a polyphenol-rich white grape extract and to a method for obtaining the extract. The extract has activity in the treatment and / or prevention of mastitis, and the invention therefore also relates to a pharmaceutical composition for intramammary administration comprising the extract, and to the use thereof in the treatment and / or prevention of mastitis in a non-human mammal.

Description

[0001]DESCRIPTION OF INTRAMAMMARY FORMULATIONS FOR MASTITIS Field of the invention The present invention falls within the field of the treatment and / or prevention of mastitis in non-human mammals. Background of the invention Mastitis, especially in cattle, is one of the most prevalent diseases in the European livestock industry, affecting 40% of cows on farms that lack mastitis control programs. Furthermore, it represents an economic burden exceeding €185 per cow per year (€1.5 billion per year in the EU). Mastitis is thus the most important disease affecting dairy cattle, not only in terms of animal health due to its high prevalence, but also because of the associated economic consequences [(Kromker V, Leimbach S.2017. Mastitis treatment-Reduction in antibiotic usage in dairy cows.Reprod Domest Anim 52 Suppl 3: 21-29); and (Nalon E, Stevenson P. 2019.Protection of Dairy Cattle in the EU: State of Play and Directions for Policymaking from a Legal and Animal Advocacy Perspective. Animals, Basel, 9). Mastitis is characterized by inflammation of the mammary gland and udder tissues due to trauma, chemical irritation, or, more commonly, infection by pathogens [(Ruegg PL.2017. A 100-Year Review: Mastitis detection, management, and prevention. J Dairy Sci 100: 10381-97); and (Gomes F, Henriques M.2016. Control of Bovine Mastitis: Old and Recent Therapeutic Approaches. Curr Microbiol 72: 377-82)]. Based on symptoms, mastitis can be classified as clinical or subclinical. Subclinical mastitis involves an increase in the somatic cell count (SCC), but without significant changes in milk characteristics. This type of mastitis does not pose a fatal risk to cows; it is less severe, but more common.It causes a reduction in milk production and quality, leading to significant economic losses. Furthermore, clinical mastitis is characterized by local signs of inflammation in the affected udder and visible abnormalities in the milk, and in some cases, it can be life-threatening for the animals [(Kromker V, Leimbach S.2017. Mastitis treatment-Reduction in antibioticusage in dairy cows. Reprod Domest Anim 52 Suppl 3: 21-29); and (Tezera M, Aman Ali E.2021.Prevalence and associated risk factors of Bovine mastitis in dairy cows in and around Assosa town, Benishangul-Gumuz Regional State, Western Ethiopia. Vet Med Sci 7: 1280-86)]. Among the microorganisms that cause mastitis are fungi, viruses, algae, and bacteria; the latter being the most common, with more than 140 different species reported. Depending on the causative microorganism or the mode of transmission, the pathology can also be classified as contagious or environmental.Contagious mastitis is primarily caused by Staphylococcus aureus (S. aureus), Streptococcus agalactiae (S. agalactiae), and Mycoplasma spp. It is transmitted between animals or between infected quarters of the same animal during milking through contaminated teat cups, the milker's hands, paper towels or cloths used to wash or dry more than one cow, and even insects such as flies. Environmental mastitis, on the other hand, is associated with different pathogens found in the environment: feces, soil, contaminated water, or milking equipment. The most frequent are Streptococcus uberis (S. uberis), Streptococcus dysgalactiae (S. dysgalactiae), Escherichia coli (E. coli), and Klebsiella spp. Antimicrobial drugs have been indispensable in the prevention and treatment of infectious diseases over the last century.However, their indiscriminate use has led to a decrease in their effectiveness and an increase in the emergence of resistant bacterial strains, becoming a global health problem. Numerous international entities, such as the World Health Organization (WHO), have identified antimicrobial resistance (AMR) as the most significant health threat of the 21st century, currently responsible for 700,000 deaths annually [(Ferri M, Ranucci E, Romagnoli P, Giaccone V. 2017. Antimicrobial resistance: A global emerging threat to public health systems. Crit Rev Food Sci Nutr 57: 2857-76); and (Xiong W, Sun Y, Zeng Z. 2018. Antimicrobial use and antimicrobial resistance in food animals. Environ Sci Pollut Res Int 25: 18377-84)]. This aligns with the European Union's "One Health" plan [EU. 2017].A European One Health Action Plan against Antimicrobial Resistance (AMR)] highlights the need to develop strategies to reduce the use of current antimicrobials and find new alternative therapies, especially in veterinary medicine, where antibiotic consumption is estimated to be twice that of humans (Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, et al. 2015. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci USA 112: 5649-54). Bacterial infections are behind most cases of bovine mastitis, and antibiotics have been central to their treatment since the industrialization of milk production. They are administered via two routes: local intramammary and / or systemic parenteral. Intramammary administration offers advantages such as achieving high local concentrations of the drug with minimal systemic absorption, thus reducing side effects (Roberson JR. 2012. Treatment of clinical mastitis).Vet Clin North Am Food Anim Pract 28: 271-88); and (Gehring R, Smith GWJJovp, therapeutics. 2006. An overview of factors affecting the disposition of intramammary preparations used to treat bovine mastitis. 294: 237-41). In Spain, there are currently 106 formulations intended for the treatment of mastitis in dairy animals, 56 of which include antibiotics. These antibiotic formulations are solutions, suspensions, or emulsions for intramammary, intramuscular, intravenous, or subcutaneous administration, and include: amoxicillin, benzylpenicillin, cephalexin, cefquinone, enrofloxacin, erythromycin, marbofloxacin, oxytetracycline, or penetamate. It is estimated that 80% of antibiotics used in dairy animals are intended for the control and treatment of mastitis worldwide (Ashraf A, Imran M.2020. Causes, types, etiological agents, prevalence, diagnosis, treatment, prevention, effects on human health and future aspects of bovine mastitis.Anim Health Res Rev 21: 36-49). However, the use of antibiotics is not entirely satisfactory since antibiotics can pass into the milk, which is undesirable, and antibiotics may require long-term treatment, which is costly in terms of lost milk production, the price of the antibiotic, and the possibility of generating resistant strains. This scenario necessitates the search for non-antibiotic alternatives for the prevention and treatment of mastitis. For this reason, the development of antimicrobial products with active ingredients of natural origin for the prevention and / or treatment of this disease is presented as an approach of great interest. Specifically, grape pomace, the pressed grapes that mainly comprises the skin, residual pulp, seeds, and stems, is an important source of natural phytochemicals (WO2014013122A1).These phytochemicals are secondary metabolites that play a role in plant defense mechanisms, including polyphenols. Polyphenols have antioxidant, anti-inflammatory, and antimicrobial properties, making them useful in the cosmetic, food, and pharmaceutical industries. Furthermore, grape cultivation is one of the most abundant in the world, generating a large amount of waste that must be treated, disposed of, or reused. Therapies based on natural extracts derived from grape pomace will allow for a reduction in the use of conventional antimicrobial agents, addressing the problem of adverse drug reactions (ADRs), improving animal health and welfare, and promoting a circular economy. The intramammary ointment “KATA MAST. ®The product “Laboratorios Ovejero SA” is the only formulation available in Spain that includes natural extracts as active ingredients, specifically extracts of Avena sativa, Calendula officinalis, Echinacea purpurea, Hypericum perforatum, Phytolacca americana, and Solidago vigaurea. However, it is a homeopathic product with no approved therapeutic indications. In other European countries, only three compositions are available on the market (Slovakia, Italy, and Bulgaria) with active ingredients other than antibiotics and / or bismuth subnitrate. These are also homeopathic products. Their active ingredients include Thymus vulgaris, Atropa belladonna, and Phytolacca decandra. None of them contain any grape pomace extract among their active ingredients. Documents GR20190100213A, EP3158868A, and AU2015202530A1 describe topical formulations for breast prevention, which They comprise vegetable oils and bismuth subnitrate as active ingredients. The documents are by Tamara Manso.et al. (Pharmaceuticals, 2023, vol. 16 (7), 950), and Tamara Manso (“Evaluation of the antibacterial activity against clinical strains of a natural extract rich in polyphenols from Albariño white grape pomace”, Doctoral Thesis, 2023) disclose grape extracts obtained with ethyl lactate. The document Rodríguez Rama, JL et al. (Environmental Science and Pollution Research International, 2021, vol. 28 (19), 24270-24278) also discloses grape extracts but without indicating the solvent used for extraction. These documents do not disclose the extraction method of the present invention, much less extracts with characteristics like those of the extracts of the present invention. Therefore, there is a need in the market for formulations for the treatment of mastitis that are not based on antibiotics, but on natural extracts from abundant and sustainable sources such as those of viticultural origin, which can be administered intramammarily.Brief Description of the Invention: The inventors of the present invention have surprisingly discovered that white grape pomace extracts exhibit activity against mastitis. The inventors have therefore developed intramammary formulations comprising white grape extracts. These formulations constitute an alternative to the usual antimicrobial treatments used in the prevention and / or treatment of mastitis in animals. To date, no intramammary formulations for the prevention and / or treatment of mastitis in animals based on white grape pomace extracts with antimicrobial activity have existed.Therefore, a first aspect of the present invention relates to a white grape extract, characterized in that it comprises gallic acid, 2,4,6-trihydrobenzoic acid, caftaric acid, procyanidin B1, procyanidin B2, procyanidin C1, catechin, epigallocatechin gallate, epicatechin, epicatechin gallate, quercetin-3-glucuronide, quercetin-3-rutinoside, quercetin-3-glucoside, kaempferol, and quercetin. A second aspect of the present invention relates to a process for obtaining a white grape extract, characterized in that it comprises the steps of: a) Providing a mixture comprising white grape pomace and optionally a dispersant; b) Eluting the mixture with a solvent comprising propylene glycol and / or acetone; c) Collecting the white grape extract obtained after elution; and d) Optionally removing the solvent.A third aspect of the present invention relates to a white grape extract, characterized in that it is an extract obtainable according to the process of the invention. A fourth aspect of the present invention relates to a pharmaceutical composition, characterized in that it is a composition for intramammary administration comprising, as an active ingredient, the white grape extract of the invention. A fifth aspect of the present invention relates to an intramammary syringe comprising the pharmaceutical composition of the invention. A sixth aspect of the present invention relates to a pharmaceutical composition for use in the treatment and / or prevention of mastitis in a non-human mammal, characterized in that it is a composition for intramammary administration comprising, as an active ingredient, the white grape extract of the invention.A seventh aspect of the present invention relates to the extract of the invention, or to the extract obtainable according to the process of the invention, for use in the treatment and / or prevention of mastitis in a non-human mammal. Brief description of the figure. Rheological behavior of the formulations of the invention compared with commercial formulations. Abscissa axis: Shear force (s. -1). Y-axis: Viscosity (Pa.s). In the graph: data “1” corresponds to commercial formulation 1 (Ilovet-clox®); data “2” corresponds to commercial formulation 2 (Mammicurine 800®); data “3” corresponds to a non-sterile formulation of the invention; and data “4” corresponds to the sterile formulation of the invention prepared aseptically. Detailed description of the invention: White grape extract. White grape pomace extracts are rich in polyphenols, exhibiting antimicrobial and antioxidant properties that can be used in the prevention and treatment of mastitis. The active ingredient of the invention is therefore a white grape extract. Thus, a first aspect of the present invention relates to a white grape extract, characterized in that it comprises gallic acid, 2,4,6-trihydrobenzoic acid, caftaric acid, procyanidin B1, procyanidin B2, procyanidin C1, catechin, epigallocatechin gallate, epicatechin,Epicatechin gallate, quercetin-3-glucuronide, quercetin-3-rutinoside, quercetin-3-glucoside, kaempferol, and quercetin. In one particular embodiment, the white grape extract is a white grape pomace extract. Grape pomace, or grape must, is the main byproduct of winemaking: the pressing of grapes comprising mainly the skin, residual pulp, seeds, and stems. The extract used in the present invention is obtained by subjecting the pomace (and optionally spent pomace) to an extraction process, which is the process of the invention. In a particular embodiment, the white grape is selected from the group consisting of albariño, albillo, arinto, chardonnay, chenin blanc, garnacha blanca, gewürztraminer, godello or gouveio, loureira, macabeo (or viura), malvasia, muscatel, müller-thurgau, riesling, roussanne, palomino, parellada, pedro ximénez, pinot blanc, Sauvignon Blanc, Silvaner, Semillon, Tocai, Trebbiano, Treixadura, Verdejo, Viognier, Xarel-Lo,or mixtures. In a preferred embodiment, the grape is selected from the group consisting of Albariño, Arinto, Godello or Gouveio, Loureira, Treixadura, or mixtures. In a further preferred embodiment, the grape is Albariño. In one particular embodiment, the white grape extract comprises a total polyphenol index of between 1000 and 45000 milligrams of gallic acid equivalents per liter of extract (mgGAE / L). In another particular embodiment, the white grape extract comprises a total polyphenol index of between 1000 and 9000 milligrams of gallic acid equivalents per liter of extract (mgGAE / L). Preferably, said extract is obtainable using propylene glycol or a propylene glycol:water mixture as a solvent. In another particular embodiment, the white grape extract comprises a total polyphenol index of between 7000 and 45000 milligrams of gallic acid equivalents per liter of extract (mgGAE / L). Preferably,This extract is obtainable using acetone as a solvent. In a more preferred embodiment, the white grape extract is a volatilized extract, obtainable using acetone as a solvent, and comprises a total polyphenol index of between 10,000 and 45,000 milligrams of gallic acid equivalents per liter of extract (mgGAE / L). In another equally preferred embodiment, the white grape extract is a non-volatilized extract, obtainable using acetone as a solvent, and comprises a total polyphenol index of between 7000 and 15000 milligrams of gallic acid equivalents per liter of extract (mgGAE / L). In one particular embodiment, the white grape extract comprises at least one of the following: - a gallic acid concentration of between 8 and 40 mg / L of extract; - a 2,4,6-trihydrobenzoic acid concentration of between 1 and 30 mg / L of extract; - a caftaric acid concentration of between 0.5 and 7 mg / L of extract.0 mg / L of extract; - a procyanidin B1+B2+C1 concentration of between 60 and 280 mg / L of extract; - a catechin concentration of between 50 and 130 mg / L of extract; - an epigallocatechin gallate concentration of between 0.1 and 3.0 mg / L of extract; - an epicatechin concentration of between 50 and 150 mg / L of extract; - an epicatechin gallate concentration of between 5 and 50 mg / L of extract; - a quercetin-3-glucuronide concentration of between 10 and 65 mg / L of extract; - a quercetin-3-rutinoside concentration of between 0.2 and 5.0 mg / L of extract; - a quercetin-3-glucoside concentration of between 10 and 120 mg / L of extract; - a kaempferol concentration of between 0.1 and 3.0 mg / L of extract; and / or a quercetin concentration of between 0.1 and 15.0 mg / L of extract. Unless otherwise indicated, the concentrations of gallic acid, 2,4,6-trihydrobenzoic acid, caftaric acid, procyanidin B1, procyanidin B2, procyanidin C1, catechin, epigallocatechin gallate,Epicatechin, epicatechin gallate, quercetin-3-glucuronide, quercetin-3-rutinoside, quercetin-3-glucoside, kaempferol, and quercetin, as indicated herein, are obtained using liquid chromatography coupled to triple quadrupole tandem mass spectrometry (LC-MS / MS_QqQ). In one particular embodiment, the white grape extract comprises a gallic acid concentration of between 10 and 40 mg / L of extract, preferably between 11 and 39 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a gallic acid concentration equal to or greater than 11 mg / L, more preferably equal to or greater than 15 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a gallic acid concentration equal to or less than 35 mg / L, more preferably equal to or less than 30 mg / L of extract.The white grape extract comprises a gallic acid concentration of between 8 and 30 mg / L of extract, preferably between 10 and 20 mg / L of extract. In a preferred embodiment thereof, the white grape extract comprises a gallic acid concentration equal to or greater than 11 mg / L, more preferably equal to or greater than 13 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a gallic acid concentration equal to or less than 19 mg / L, more preferably equal to or less than 17 mg / L of extract. In a particular embodiment, the white grape extract comprises a 2,4,6-trihydrobenzoic acid concentration of between 1 and 5 mg / L of extract, preferably between 1 and 3 mg / L of extract. In a preferred embodiment thereof, the white grape extract comprises a 2,4,6-trihydrobenzoic acid concentration equal to or greater than 1.5 mg / L.In a preferred embodiment, compatible with the foregoing, the white grape extract comprises a 2,4,6-trihydrobenzoic acid concentration of 4 mg / L of extract or less, more preferably 3 mg / L of extract or less. In another particular embodiment, the white grape extract comprises a 2,4,6-trihydrobenzoic acid concentration of between 1 and 35 mg / L of extract, preferably between 2 and 30 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a 2,4,6-trihydrobenzoic acid concentration of 3 mg / L of extract or more, more preferably 4 mg / L of extract or more. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a 2,4,6-trihydrobenzoic acid concentration of 10 mg / L of extract or less, more preferably 8 mg / L of extract or less. In a particular embodiment,the white grape extract comprises a concentration ofcaftaric acid of between 4 and 7 mg / L of extract, preferably between 5 and 7 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a concentrationof caftaric acid equal to or greater than 5.2, more preferably equal to or greater than 5.5 mg / L ofextract. In another preferred embodiment, compatible with the foregoing, the white grape extractcomprises a caftaric acid concentration equal to or less than 6.5, more preferablyequal to or less than 6 mg / L of extract extract, preferably between 0.10 and 3.50 mg / Lde extract. In a preferred embodiment of the foregoing, the white grape extract comprises a caftaric acid concentration equal to or greater than 0.20, more preferably equal to or greater than 0.40 mg / L of extract. In another preferred embodiment,In a preferred embodiment, the white grape extract comprises a caftaric acid concentration of 3.00 mg / L or less, more preferably 2.00 mg / L or less. In one particular embodiment, the white grape extract comprises a procyanidin concentration of B1+B2+C1 of between 60 and 130 mg / L of extract, preferably between 65 and 125 mg / L of extract. In a preferred embodiment of the above, the white grape extract comprises a procyanidin concentration of B1+B2+C1 of 70 mg / L or more, more preferably 75 mg / L or more. In another preferred embodiment, compatible with the above, the white grape extract comprises a procyanidin concentration of B1+B2+C1 of 120 mg / L or less, more preferably 100 mg / L or less. In another particular embodiment, the white grape extract comprises a procyanidin concentration of B1+B2+C1 of between 90 and 280 mg / L of extract,preferably between 100 and 270 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a procyanidin concentration of B1+B2+C1 equal to or greater than 105, more preferably equal to or greater than 110 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a procyanidin concentration of B1+B2+C1 equal to or less than 230, more preferably equal to or less than 200 mg / L of extract. In a particular embodiment, the white grape extract comprises a catechin concentration of between 50 and 70 mg / L of extract, preferably between 53 and 69 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a catechin concentration equal to or greater than 54, more preferably equal to or greater than 55 mg / L of extract. In another preferred embodiment, compatible with the foregoing,The white grape extract comprises a catechin concentration equal to or less than 65 mg / L, more preferably equal to or less than 60 mg / L of extract. In another particular embodiment, the white grape extract comprises a catechin concentration of between 50 and 130 mg / L of extract, preferably between 50 and 125 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a catechin concentration equal to or greater than 55 mg / L, more preferably equal to or greater than 60 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a catechin concentration equal to or less than 120 mg / L, more preferably equal to or less than 115 mg / L of extract. In a particular embodiment, the white grape extract comprises an epigallocatechin gallate concentration of between 0.1 and 3.0 mg / L of extract, preferably between 0.1 and 2.6 mg / L of extract. In a preferred embodiment of the foregoing,The white grape extract comprises an epigallocatechin gallate concentration equal to or greater than 0.5 mg / L, more preferably equal to or greater than 1.0 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises an epigallocatechin gallate concentration equal to or less than 2.5 mg / L, more preferably equal to or less than 2.0 mg / L of extract. In another particular embodiment, the white grape extract comprises an epigallocatechin gallate concentration of between 0.05 and 1.20 mg / L of extract, preferably between 0.05 and 1.00 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises an epigallocatechin gallate concentration equal to or greater than 0.10 mg / L, more preferably equal to or greater than 0.20 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises an epigallocatechin gallate concentration equal to or less than 0.70,more preferably equal to or less than 0.50 mg / L of extract. In one particular embodiment, the white grape extract comprises an epicatechin concentration of between 50 and 70 mg / L of extract, preferably between 55 and 68 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises an epicatechin concentration equal to or greater than 57 mg / L of extract, more preferably equal to or greater than 63 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises an epicatechin concentration equal to or less than 65 mg / L of extract, more preferably equal to or less than 63 mg / L of extract. In another particular embodiment, the white grape extract comprises an epicatechin concentration of between 10 and 150 mg / L of extract, preferably between 10 and 140 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises an epicatechin concentration equal to or greater than 30 mg / L of extract.More preferably equal to or greater than 60 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises an epicatechin concentration equal to or less than 130 mg / L, more preferably equal to or less than 125 mg / L of extract. In one particular embodiment, the white grape extract comprises an epicatechin gallate concentration of between 3 and 20 mg / L of extract, preferably between 5 and 20 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises an epicatechin gallate concentration equal to or greater than 6 mg / L, more preferably equal to or greater than 7 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises an epicatechin gallate concentration equal to or less than 17 mg / L, more preferably equal to or less than 12 mg / L of extract. In another particular embodiment,The white grape extract comprises an epicatechin gallate concentration of between 5 and 50 mg / L of extract, preferably between 5 and 45 mg / L of extract. In a preferred embodiment thereof, the white grape extract comprises an epicatechin gallate concentration equal to or greater than 10 mg / L of extract, more preferably equal to or greater than 13 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises an epicatechin gallate concentration equal to or less than 40 mg / L of extract, more preferably equal to or less than 35 mg / L of extract. In a particular embodiment, the white grape extract comprises a quercetin-3-glucuronide concentration of between 10 and 25 mg / L of extract, preferably between 15 and 20 mg / L of extract. In a preferred embodiment thereof, the white grape extract comprises a quercetin-3-glucuronide concentration equal to or greater than 15 mg / L of extract.more preferably equal to or greater than 16 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a quercetin-3-glucuronide concentration equal to or less than 19 mg / L, more preferably equal to or less than 18 mg / L of extract. In another particular embodiment, the white grape extract comprises a quercetin-3-glucuronide concentration of between 25 and 65 mg / L of extract, preferably between 28 and 60 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a quercetin-3-glucuronide concentration equal to or greater than 30 mg / L, more preferably equal to or greater than 32 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a quercetin-3-glucuronide concentration equal to or less than 55 mg / L, more preferably equal to or less than 45 mg / L of extract. In a particular embodiment,The white grape extract comprises a quercetin-3-rutinoside concentration of between 0.2 and 1.0 mg / L of extract, preferably between 0.3 and 0.8 mg / L of extract. In a preferred embodiment thereof, the white grape extract comprises a quercetin-3-rutinoside concentration equal to or greater than 0.4 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a quercetin-3-rutinoside concentration equal to or less than 0.7 mg / L of extract. In another particular embodiment, the white grape extract comprises a quercetin-3-rutinoside concentration of between 1 and 5 mg / L of extract, preferably between 2 and 5 mg / L of extract. In a further preferred embodiment, the white grape extract comprises a quercetin-3-rutinoside concentration equal to or greater than 3 mg / L of extract. In another preferred embodiment, compatible with the above,The white grape extract comprises a quercetin-3-rutinoside concentration of 4 mg / L of extract or less. In one particular embodiment, the white grape extract comprises a quercetin-3-glucoside concentration of between 10 and 25 mg / L of extract, preferably between 11 and 21 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a quercetin-3-glucoside concentration of 11 mg / L or more, more preferably 15 mg / L or more. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a quercetin-3-glucoside concentration of 21 mg / L or less, more preferably 19 mg / L or less. In another particular embodiment, the white grape extract comprises a quercetin-3-glucoside concentration of between 25 and 130 mg / L of extract, preferably between 30 and 120 mg / L of extract. In a preferred embodiment thereof,The white grape extract comprises a quercetin-3-glucoside concentration of 35 mg / L or higher, more preferably 40 mg / L or higher. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a quercetin-3-glucoside concentration of 100 mg / L or lower, more preferably 60 mg / L or lower. In one particular embodiment, the white grape extract comprises a kaempferol concentration of between 0.1 and 3.0 mg / L, preferably between 0.2 and 2.5 mg / L. In a preferred embodiment of the foregoing, the white grape extract comprises a kaempferol concentration of 0.2 mg / L or higher, more preferably 0.5 mg / L or higher. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a kaempferol concentration of 2.1 mg / L or lower, more preferably 1 mg / L or lower.5 mg / L of extract. In another particular embodiment, the white grape extract comprises a kaempferol concentration of between 0.1 and 2.5 mg / L of extract, preferably between 0.2 and 2.0 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a kaempferol concentration equal to or greater than 0.3 mg / L, more preferably equal to or greater than 0.5 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a kaempferol concentration equal to or less than 1.5 mg / L, more preferably equal to or less than 1.0 mg / L of extract. In a particular embodiment, the white grape extract comprises a quercetin concentration of between 1.0 and 5.0 mg / L of extract, preferably between 1.5 and 4.5 mg / L of extract. In a preferred embodiment of the above, the white grape extract comprises a quercetin concentration equal to or greater than 1.5, more preferably equal to or greater than 2.0 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a quercetin concentration equal to or less than 4.5 mg / L, more preferably equal to or less than 4.0 mg / L of extract, and even more preferably equal to or less than 3.5 mg / L of extract. In another particular embodiment, the white grape extract comprises a quercetin concentration of between 0.1 and 15.0 mg / L of extract, preferably between 0.3 and 15.0 mg / L of extract. In a preferred embodiment of the foregoing, the white grape extract comprises a quercetin concentration equal to or greater than 0.4 mg / L, more preferably equal to or greater than 0.5 mg / L of extract. In another preferred embodiment, compatible with the foregoing, the white grape extract comprises a quercetin concentration equal to or less than 12 mg / L, more preferably equal to or less than 5 mg / L of extract, and even more preferably equal to or less than 2 mg / L of extract. In a particular embodiment,The white grape extract comprises at least one of the following: - a gallic acid concentration of between 10 and 40 mg / L of extract; - a 2,4,6-trihydrobenzoic acid concentration of between 1 and 5 mg / L of extract; - a caftaric acid concentration of between 4 and 7 mg / L of extract; - a procyanidin B1+B2+C1 concentration of between 60 and 130 mg / L of extract; - a catechin concentration of between 50 and 70 mg / L of extract; - an epigallocatechin gallate concentration of between 0.1 and 3.0 mg / L of extract; - an epicatechin concentration of between 50 and 70 mg / L of extract; - an epicatechin gallate concentration of between 3 and 20 mg / L of extract; - a quercetin-3-glucuronide concentration of between 10 and 25 mg / L of extract; a concentration of quercetin-3-rutinoside of between 0.2 and 1.0 mg / L of extract; - a concentration of quercetin-3-glucoside of between 10 and 25 mg / L of extract; - a concentration of kaempferol of between 0,1 and 3 mg / L of extract; and / or a quercetin concentration of between 1.0 and 5.0 mg / L of extract. In a preferred embodiment, compatible with the above, the white grape extract comprises: - a procyanidin concentration of between 60 and 130 mg / L of extract; - a quercetin-3-glucuronide concentration of between 10 and 25 mg / L of extract; - a quercetin-3-rutinoside concentration of between 0.2 and 1.0 mg / L of extract; - a quercetin-3-glucoside concentration of between 10 and 25 mg / L of extract; In a preferred embodiment, compatible with the above, the white grape extract comprises: - a procyanidin concentration of between 60 and 130 mg / L of extract; - a catechin concentration of between 50 and 70 mg / L of extract; - an epicatechin concentration of between 50 and 70 mg / L of extract; and- an epicatechin gallate concentration of between 3 and 20 mg / L of extract. In a more preferred embodiment, compatible with the above,The white grape extract comprises: - a gallic acid concentration of between 10 and 40 mg / L of extract; - a 2,4,6-trihydrobenzoic acid concentration of between 1 and 5 mg / L of extract; - a caftaric acid concentration of between 4 and 7 mg / L of extract; - a procyanidin B1+B2+C1 concentration of between 60 and 130 mg / L of extract; - a catechin concentration of between 50 and 70 mg / L of extract; - an epigallocatechin gallate concentration of between 0.1 and 3.0 mg / L of extract; - an epicatechin concentration of between 50 and 70 mg / L of extract; - an epicatechin gallate concentration of between 3 and 20 mg / L of extract; - a quercetin-3-glucuronide concentration of between 10 and 25 mg / L of extract; - a concentration of quercetin-3-rutinoside between 0.2 and 1.0 mg / L of extract; - a concentration of quercetin-3-glucoside between 10 and 25 mg / L of extract; - a concentration of kaempferol between 0,1 and 3 mg / L of extract; and - a quercetin concentration of between 1.0 and 5.0 mg / L of extract. In another particular embodiment, the white grape extract comprises at least one of the following: - a gallic acid concentration of between 8 and 30 mg / L of extract; - a 2,4,6-trihydrobenzoic acid concentration of between 1 and 35 mg / L of extract; - a caftaric acid concentration of between 0.05 and 4.00 mg / L of extract; - a procyanidin B1+B2+C1 concentration of between 90 and 280 mg / L of extract; - a catechin concentration of between 50 and 130 mg / L of extract; - an epigallocatechin gallate concentration of between 0.05 and 1,20 mg / L of extract; - an epicatechin concentration of between 10 and 150 mg / L of extract; - an epicatechin gallate concentration of between 5 and 50 mg / L of extract; - a quercetin-3-glucuronide concentration of between 25 and 65 mg / L of extract; - a quercetin-3-rutinoside concentration of between 1 and 5 mg / L of extract; - a quercetin-3-glucoside concentration of between 25 and 130 mg / L of extract; - a kaempferol concentration of between 0.1 and 2.5 mg / L of extract; and / or - a quercetin concentration of between 0.1 and 15.0 mg / L of extract. In another preferred embodiment, compatible with the foregoing,The white grape extract comprises: - a concentration of procyanidins B1+B2+C1 of between 90 and 280 mg / L of extract; - a concentration of quercetin-3-glucuronide of between 25 and 65 mg / L of extract; - a concentration of quercetin-3-rutinoside of between 1 and 5 mg / L of extract; and - a concentration of quercetin-3-glucoside of between 25 and 130 mg / L of extract. In another preferred embodiment, compatible with the above, the white grape extract comprises: - a concentration of procyanidins B1+B2+C1 of between 90 and 280 mg / L of extract; - a concentration of catechin of between 50 and 130 mg / L of extract; - a concentration of epicatechin of between 10 and 150 mg / L of extract; and- an epicatechin gallate concentration of between 5 and 50 mg / L of extract. In another more preferred embodiment, compatible with the above,The white grape extract comprises: - a gallic acid concentration of between 8 and 30 mg / L of extract; - a 2,4,6-trihydrobenzoic acid concentration of between 1 and 35 mg / L of extract; - a caftaric acid concentration of between 0.05 and 4.00 mg / L of extract; - a procyanidin B1+B2+C1 concentration of between 90 and 280 mg / L of extract; - a catechin concentration of between 50 and 130 mg / L of extract; - an epigallocatechin gallate concentration of between 0.05 and 1.20 mg / L of extract; - an epicatechin concentration of between 10 and 150 mg / L of extract; - an epicatechin gallate concentration of between 5 and 50 mg / L of extract; - a quercetin-3-glucuronide concentration of between 25 and 65 mg / L of extract; - a concentration of quercetin-3-rutinoside of between 1 and 5 mg / L of extract; - a concentration of quercetin-3-glucoside of between 25 and 130 mg / L of extract; - a concentration of kaempferol of between 0.1 and 2,5 mg / L of extract; and a quercetin concentration of between 0.1 and 15.0 mg / L of extract. In a particular embodiment of the white grape extract of the first aspect of the invention, it is characterized in that it comprises at least one organic acid selected from the group consisting of citric acid, quinic acid, malic acid, azelaic acid, ascorbic acid, maleic acid, and succinic acid. Preferably, the white grape extract comprises citric acid, quinic acid, malic acid, azelaic acid, ascorbic acid, maleic acid, and succinic acid. In one particular embodiment, the white grape extract comprises at least one of the following: - a citric acid concentration of between 12 and 150 mg / L of extract; - a quinic acid concentration of between 0.15 and 1.0 mg / L of extract; - a malic acid concentration of between 100 and 210 mg / L of extract; - an azelaic acid concentration of between 0.20 and 0.22 mg / L of extract; - an ascorbic acid concentration of between 0,8 and 1.1 mg / L of extract; - a maleic acid concentration of between 150 and 240 mg / L of extract; and / or - a succinic acid concentration of between 2 and 25 mg / L of extract. In another particular embodiment, the white grape extract comprises at least one of the following: - a citric acid concentration of between 130 and 150 mg / L of extract; - a quinic acid concentration of between 0.8 and 1.0 mg / L of extract; - a malic acid concentration of between 190 and 210 mg / L of extract; - an ascorbic acid concentration of between 0.96 and 1.1 mg / L of extract; - a maleic acid concentration of between 210 and 235 mg / L of extract; and / or a succinic acid concentration of between 2 and 4 mg / L of extract. In another particular embodiment, the white grape extract comprises at least one of the following: - a citric acid concentration of between 13 and 15 mg / L of extract; - a quinic acid concentration of between 0.16 and 0.19 mg / L of extract; - a malic acid concentration of between 110 and 130 mg / L of extract; - an azelaic acid concentration of between 0.20 and 0.22 mg / L of extract; - an ascorbic acid concentration of between 0.835 and 0.840 mg / L of extract; - a maleic acid concentration of between 170 and 190 mg / L of extract; and / or a succinic acid concentration of between 24.2 and 25 mg / L of extract. Unless otherwise indicated, the concentrations of citric acid, quinic acid, malic acid, azelaic acid, ascorbic acid, maleic acid, and succinic acid indicated herein are obtained using UHPLC-QTOF. In a particular embodiment of the white grape extract of the first aspect of the invention, it is characterized in that it comprises at least one sugar selected from the group consisting of glucose, sucrose, and sorbitol. Preferably, the white grape extract comprises at least glucose and sucrose. In a particular embodiment,The white grape extract comprises at least one of the following: - a glucose concentration of between 1810 and 2250 mg / L of extract; - a sucrose concentration of between 2 and 6 mg / L of extract; and / or - a sorbitol concentration of between 8 and 11 mg / L of extract. In another particular embodiment, the white grape extract comprises at least one of the following: - a glucose concentration of between 2200 and 2250 mg / L of extract; and / or - a sucrose concentration of between 2.0 and 2.9 mg / L of extract; and / or - a sorbitol concentration of between 9 and 11 mg / L of extract. In another particular embodiment, the white grape extract comprises at least one of the following: - a glucose concentration of between 1810 and 2000 mg / L of extract; - a sucrose concentration of between 5.5 and 6.0 mg / L of extract; and / or a sorbitol concentration of between 8 and 11 mg / L of extract. Unless otherwise indicated, glucose concentrations,The sucrose and sorbitol indicated herein are obtained using UHPLC-QTOF. In one particular embodiment, the grape extract of the invention is characterized in that it comprises linoleic acid and / or linolenic acid at a concentration of less than 0.10 mg / L, preferably less than 0.05 mg / L, and even more preferably less than 0.01 mg / L, using the UHPLC-QTOF technique. In another particular embodiment, the grape extract of the invention is characterized in that it does not comprise linoleic acid and / or linolenic acid, preferably not comprising linoleic acid and linolenic acid. In a more preferred embodiment, the grape extract of the invention is characterized in that it does not comprise an essential fatty acid. In the context of this paragraph, the expression “does not comprise” is to be understood as synonymous with the fact that these acids are not detected using the UHPLC-QTOF technique. In the present invention, the transitional expression “comprises” is used as an open-ended expression.whose interpretation is broader than when the closed-type expression “consists of” is used. A claim that includes the expression “consists of” is limited solely to the technical elements defined in that claim and cannot be interpreted as encompassing any other element. On the other hand, a claim that contains the open-type expression “comprises” must be interpreted in the broadest sense and may (or may not) include other technical elements not explicitly mentioned, in addition to those explicitly defined, which are the essential technical elements of the invention. In a particular embodiment of all aspects described herein, and unless expressly stated otherwise, the term “comprises” may be replaced by “consists of,” in which case the considerations of the preceding paragraph would apply. In a particular embodiment,The white grape extract is characterized by the absence of anthocyanins. “Anthocyanins” refers to a group of flavonoid polyphenols comprising anthocyanins and anthocyanidins, which also includes the oxide combinations of an anthocyanidin with a sugar. They are responsible for the bluish-red color of the skin of red grapes. In another particular embodiment, the white grape extract is characterized by a pH between 4 and 8 measured in aqueous solution. The grape extract of the invention is applicable in the treatment of mastitis, preferably in a pharmaceutical composition for injection. Thus, in one particular embodiment, the extract is in solution, suspension, emulsion, or solid form, as a powder or paste (obtainable, for example, by freeze-drying or spray-drying). Water may optionally be added to the organic solvent extraction process.However, the grape pomace used as raw material for extraction already contains residual moisture. Thus, in a preferred embodiment, the grape extract of the invention is an aqueous extract. The organic solvent used in the extraction may evaporate, resulting in a white grape extract comprising water. Those skilled in the art will understand that the organic solvent may evaporate completely or partially. In this context, the extract comprises no more than 60% organic solvent, no more than 50% organic solvent, no more than 40% organic solvent, no more than 20% organic solvent, no more than 10% organic solvent, no more than 5% organic solvent, no more than 1% organic solvent, and preferably no more than 0.5% organic solvent. In a particular embodiment, the grape extract of the invention is an extract that does not contain organic solvents.or contains only traces thereof. In a preferred embodiment, the grape extract of the invention is an extract containing only water as a solvent. If no water is added during the process, the aqueous extract comprises water derived from the residual moisture of the pomace itself. Method of Obtaining The second aspect of the present invention relates to a method for obtaining a white grape extract characterized in that it comprises the steps of: a) Providing a mixture comprising white grape pomace and optionally a dispersant; b) Eluting the mixture with a solvent comprising propylene glycol and / or acetone; c) Collecting the white grape extract obtained after elution; and d) Optionally removing the solvent. The extraction process for obtaining the extract of the invention is carried out according to the method described in WO 2014013122 A1.but using elution solvents that had not been previously described. This adaptation exhibits two main advantages. On the one hand, the extract obtained comprises a distinct polyphenolic composition, which is very useful in the treatment of mastitis. On the other hand, the extract obtained can be easily volatilized, resulting in an aqueous extract that can be used directly in injectable compositions. In the present invention, “dispersant” is a solid material that can optionally be mixed with the bagasse. Mixing with a biological sample (such as bagasse) allows for its disruption and dispersion on its surface, so that the mechanical mixing disturbs the architecture of the sample, breaking the material into smaller pieces and increasing the release of the chemical compounds present inside the plant cells of the sample. In a particular embodiment of step (a),The white grape pomace is provided pre-crushed. In one particular embodiment, step (a) of the process comprises providing a mixture comprising white grape pomace and a dispersant. Preferably, the dispersant is selected from the group consisting of sand, Florisil, C18, alumina, and silica gel. More preferably, the dispersant is sand, and even more preferably sand of natural origin. In one particular embodiment, the grain size of the dispersant is selected from between 100 µm and 1 mm, preferably from between 250 µm and 320 µm. In another preferred embodiment, from between 0.5 and 0.8 mm. In a particular embodiment, step (a) of the process comprises providing a mixture comprising white grape pomace and a dispersant, wherein the dispersant:pomace ratio (by mass) is between 0.5:1 and 1:10, preferably between 0.5:1 and 1:7, more preferably between 0.5:1 and 1:5, and even more preferably between 0.8:1 and 1:5. If a dispersant is included, the preparation of the mixture in step (a), comprising white grape residue and a dispersant, can be carried out using a mortar (glass, porcelain, agate), a blade disruptor, grinding equipment, a crusher, a rotary drum, or any other device that allows the mixture to be mechanically crushed and homogenized. In one particular embodiment, step (a) takes place within a temperature range of 10°C to 40°C. In another particular embodiment, step (a) takes place at atmospheric pressure. These embodiments prevent the risk of degradation of the compounds to be extracted. In one particular embodiment, the dispersant and the pomace are mixed at a temperature of 10 to 40°C and / or at a pressure of 0.8–1.2 atm. In one particular embodiment, the solvent in step (b) is in a proportion of 0.2 to 10 volumes of solvent relative to the weight of the mixture comprising white grape pomace and, if present, the dispersant, preferably between 0.2 and 6. In one particular embodiment, step (b) includes keeping the solvent in contact with the mixture for between 1 and 72 hours, preferably between 24 and 72 hours, more preferably between 48 and 72 hours. In another particular embodiment, this step is carried out at a temperature between 10°C and 40°C. In another particular embodiment, the extraction solvent comprising propylene glycol and / or acetone further comprises a solvent selected from the group consisting of water, alkyl alcohol, glycols, or mixtures thereof, preferably solvents having a boiling point not exceeding 80°C. In the present invention, “alkyl alcohol” refers to a substance with a linear or branched hydrocarbon chain containing a hydroxyl group, of between 1 and 12 carbon atoms,preferably having between 1 and 6 carbon atoms. In a particular embodiment, the alkyl alcohol is selected from methanol, ethanol, isopropanol, and mixtures thereof. In the present invention, “glycols” refers to a substance with a linear or branched hydrocarbon chain containing two or more hydroxyl groups, having between 2 and 12 carbon atoms, preferably between 2 and 8 carbon atoms, and optionally containing one or more ether groups. In one particular embodiment, the glycol is selected from 1,2-ethanediol (ethylene glycol), propane-1,2-diol (propylene glycol), butane-1,4-diol (1,4-butylene glycol), butane-1,3-diol, 1,5-pentanediol (pentylene glycol), 2-methyl-2,4-pentanediol (hexylene glycol), 2-(2-ethoxyethoxy)ethanol (diethylene glycol monoethyl ether), 2,2'-dihydroxydipropyl ether (dipropylene glycol), and 1,2-octanediol (caprylyl glycol). In a preferred embodiment, the solvent in step (b) also comprises water. In one particular embodiment,The solvent in step (b) comprises acetone. Preferably, acetone and water. In another particular embodiment, the solvent in step (b) comprises propylene glycol. Preferably, propylene glycol and water. In one particular embodiment, the extraction solvent either comprises propylene glycol or acetone. In a preferred embodiment, if the solvent comprises propylene glycol, then it does not comprise acetone. In another preferred embodiment, compatible with the foregoing, if the solvent comprises acetone, then it does not comprise propylene glycol. In one particular embodiment, the solvent in step (b) may have a modified pH of between 0.5 and 3. Thus, in one particular embodiment, the solvent in step (b) further comprises an organic or inorganic acid, preferably an acid selected from the group consisting of hydrochloric acid, acetic acid, phosphoric acid, formic acid, and mixtures thereof. In another particular embodiment,The eluates collected in step (c) are used to repeat the elution of the extract. Recirculating the eluates collected in step (c) reduces the total volume of solvent used in the process. While not a necessary feature for the proper functioning of the invention, an additional advantage associated with recirculating the eluates is the potential increase in the amount of total polyphenols extracted from the white grape pomace. Thus, in a particular embodiment, step (c) comprises, in addition to collecting the eluates, recirculating said eluates through the mixture comprising the white grape pomace, repeating the elution with the solvent between 1 and 7 times, preferably 3, 4, or 5 times. In other words, in a particular embodiment, the process of the invention is characterized in that, after collecting the white grape extract, step (c) further comprises recirculating the eluate obtained.by the mixture of step (a). This embodiment corresponds to the repetition of the method of step (b), but wherein the mixture of step (a) comprises grape pomace previously subjected at least once to solvent elution, and using a solvent that has already been used at least once in the elution. This embodiment is repeated such that the solvent is recirculated through the mixture. The combination of the maceration and eluate recirculation steps allows for an optimized procedure in terms of the yield of the extract obtained and low solvent consumption. Step (d) is an optional solvent removal step, preferably of the organic solvent. In a particular embodiment of the process of the invention, step (d) is not carried out, or is carried out to remove a portion of the organic solvent, such that the extract is obtained with an amount of organic solvent of no more than 60%.no more than 50% organic solvent, preferably no more than 40% organic solvent. In a preferred embodiment of the foregoing, the organic solvent is propylene glycol. In a particular embodiment, if acetone is used as the organic solvent in step (b), then the extraction process comprises step (d), characterized by being an acetone removal step. The solvent removal in step (d) may be partial or complete. In this step, the white grape pomace extract obtained after the elution(s) is subjected to a concentration step, i.e., a process for reducing the amount of solvent. In a particular embodiment, step (d) comprises solvent removal to a final amount of no more than 20% organic solvent, no more than 10% organic solvent, no more than 5% organic solvent, preferably no more than 1% organic solvent.and even more preferably not more than 0.5% organic solvent. In a preferred embodiment, step (d) is an organic solvent evaporation step, preferably a complete organic solvent evaporation step, such that the organic solvent is totally or essentially totally removed. In the context of the present invention, organic solvent evaporation is synonymous with organic solvent volatilization, preferably acetone. In a further preferred embodiment, in step (d) the organic solvent is totally or essentially totally evaporated, thereby obtaining an aqueous extract as a product. The process for removing the organic solvent is known to those skilled in the art, for example, by simply leaving the extract at ambient temperature and atmospheric pressure, under a stream of nitrogen, with added heat, under vacuum, in a vacuum rotary evaporator, in a thin-film evaporator,Among others. Extracts can also be obtained as a solid product. Thus, in another particular embodiment, the extraction process further comprises a freeze-drying step or a spray-drying step. This step may be an additional step after step (c). Alternatively, it may be an additional step after step (d), i.e., freeze-drying or spray-drying requires the removal of the organic solvent as a prior step, or it may be step (d) itself, in which case the spray-drying directly removes the organic solvent. In a preferred embodiment of the above, when the process comprises a freeze-drying step, this step is carried out after step (d), i.e.,Freeze-drying requires the removal of organic solvent as a preliminary step. In freeze-drying, it is possible to pre-freeze the collected eluates or to freeze the eluates after solvent evaporation. In one particular embodiment, freeze-drying is carried out between -50 °C and -20 °C, preferably between -45 °C and -35 °C. In one particular embodiment, freeze-drying is carried out between 1.31 × 10, -6 atm and 6.6 × 10 -6 atm (0.001 to 0.005 mmHg), preferably between 1.31 × 10 -6 atm and 1.31 × 10 -5atm (0.001 to 0.01 mmHg). The extract is stable, and the addition of stabilizers is not necessary during the freeze-drying stage. However, small amounts of sugars at a concentration ranging from 1% to 5% or other molecules acting as cryoprotectants and / or freeze-dryers may be added. In one particular embodiment, the sugars are selected from the group consisting of glucose, sucrose, trehalose, maltodextrin, gum arabic, and xanthan gum. The extract of the invention remains unchanged after freeze-drying. In spray drying, the collected eluates, or the eluates after solvent evaporation, are transformed into a dry powder by rapid drying with hot air or an inert gas. This method yields materials with a fine and consistent particle size. In one particular embodiment, spray drying is carried out with an air flow between 15000 and 60000 L / h.In another particular embodiment, spray drying is carried out with a feed flow rate of between 1 L / h and 500 L / h, preferably between 1 L / h and 100 L / h, more preferably between 1 L / h and 20 L / h. In another particular embodiment, spray drying is carried out with an air pressure of between 2 and 10 bar. In another particular embodiment, spray drying is carried out at a drying temperature of between 150 and 200 °C and an inlet temperature of between 15 and 35 °C. In one particular embodiment, solvent removal comprises recovering the solvent for subsequent reuse in step (b), extraction. The process of the invention allows obtaining a white grape pomace extract comprising polyphenols. Thus, a third aspect of the present invention relates to a white grape extract characterized in that it is obtainable according to the process of the invention.“Obtainable extract” or “obtained extract” means the product obtained as a result of applying the process of the invention, with the technical elements inherent to the process. In one particular embodiment, the extract is obtained by using acetone as an extraction solvent. Thus, in a preferred embodiment, the white grape extract obtainable according to the process of the invention is an extract comprising acetone. In a further preferred embodiment, the acetone is completely evaporated, and the grape extract obtainable according to the process of the invention is an aqueous extract. In another particular embodiment, the extract is obtained by using propylene glycol as an extraction solvent. Thus, in yet another preferred embodiment, the white grape extract obtainable according to the process is an extract comprising propylene glycol.All the embodiments described above for the process, and also for the extract, are applicable to this third aspect of the invention. Pharmaceutical Composition A fourth aspect of the present invention relates to a pharmaceutical composition characterized in that it is a composition for intramammary administration comprising a white grape extract of the invention as the active ingredient. In one particular embodiment, the white grape extract of the pharmaceutical composition is the white grape extract of the invention, or the white grape extract obtained according to the process of the invention. In another particular embodiment, the pharmaceutical composition is characterized in that it is an injectable composition. In this embodiment, the pharmaceutical composition is formulated as an injectable composition for intramammary injection.Therefore, in the present invention, the composition can be formulated as a solution, emulsion, suspension, dispersion, or any other form suitable for injection. Preferably, the composition is formulated as an emulsion or dispersion. In the case of an emulsion, the composition comprises an aqueous phase, an oily phase, and a surfactant. The grape extract, which is the active ingredient, corresponds to the aqueous phase, while the oily phase comprises a fat or oil suitable as an excipient for injection. In a particular embodiment, the aqueous phase comprises purified water for injection, physiological saline solution, lower alcohols (ethanol, isopropanol, propanol), and / or higher alcohols (glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol).In a preferred embodiment, the aqueous phase comprises purified water for injection, physiological saline solution, ethanol, isopropanol, propanol, glycerin, and / or propylene glycol, more preferably purified water for injection, ethanol, isopropanol, propanol, and / or propylene glycol. In the context of the present invention, the aqueous extract may comprise traces of an organic solvent, preferably acetone. Alternatively, the aqueous extract may comprise an organic solvent. Thus, in a particular embodiment, the extract comprises no more than 60% organic solvent, no more than 50% organic solvent, no more than 40% organic solvent, no more than 20% organic solvent, no more than 10% organic solvent, no more than 5% organic solvent, no more than 1% organic solvent, and preferably no more than 0.5% organic solvent. In a particular embodiment, the oil is a mineral or vegetable oil.In a preferred embodiment, the fat or oil is selected from the group consisting of paraffin oil, peanut oil, soybean oil, sesame oil, hydrogenated polyisobutene, corn oil, olive oil, mono-, di-, or triglycerides of medium-chain fatty acids (6 to 12 carbon atoms), capric / caprylic triglyceride, castor oil, cottonseed oil, grapeseed oil, safflower oil, peanut oil, poppyseed oil, rapeseed oil, sunflower oil, palm oil, castor oil, and mixtures thereof.In another more preferred embodiment, the fat or oil is selected from the group consisting of paraffin oil, soybean oil, sesame oil, hydrogenated polyisobutene, corn oil, olive oil, mono-, di-, or triglycerides of medium-chain fatty acids (6 to 12 carbon atoms), capric / caprylic triglyceride, castor oil, cottonseed oil, grapeseed oil, safflower oil, peanut oil, poppyseed oil, rapeseed oil, sunflower oil, palm oil, castor oil, and mixtures thereof. The mono-, di-, or triglyceride of medium-chain fatty acid (6 to 12 carbon atoms) may be selected from the group of compounds consisting of glycerol bonded to at least one fatty acid.Examples of fatty acids include hexanoic acid (caproic acid), octanoic acid (caprylic acid), nonanoic acid (pelargonic acid), decanoic acid (capric acid), undecanoic acid (undecyl acid), and dodecanoic acid (lauric acid). Preferred examples of fatty acids are hexanoic acid (caproic acid), octanoic acid (caprylic acid), undecanoic acid (undecyl acid), and dodecanoic acid (lauric acid). In a preferred embodiment, the oil phase does not comprise a fatty acid glyceride. In another preferred embodiment, the oil phase is not peanut oil. In a preferred embodiment, the oil is paraffin oil. In a particular embodiment, the active ingredient is grape extract, while the oil is the excipient comprising the oil phase. This excipient is not a biologically active oil.In another embodiment compatible with all the foregoing, the oil is an excipient that does not comprise active ingredients exhibiting biological activity against mastitis. In a preferred embodiment, the pharmaceutical composition of the invention is characterized in that it is an emulsion comprising an aqueous phase, an oil phase, and a surfactant, wherein: - the aqueous phase comprises purified water for injection, ethanol, isopropanol, propanol, propylene glycol, or mixtures thereof; and / or - the oil phase comprises paraffin oil, peanut oil, or mixtures thereof. In a particular embodiment, the composition comprises the oil in an amount of 0.5 to 8%, preferably 1 to 6%, more preferably 2.5 to 5%, with respect to the total weight of the composition.In one particular embodiment, the ratio between the oil phase and the aqueous phase (which may be, for example, paraffin oil as the oil phase and propylene glycol extract:water as the aqueous phase) is 1:0.1-1, preferably 1:0.1-0.9, 1:0.1-0.8, 1:0.1-0.7, 1:0.1-0.6, 1:0.1-0.5, 1:0.2-0.5, more preferably 1:0.2-0.4, or even more preferably 1:0.3. In a preferred embodiment, the ratio between the oil phase and the aqueous phase is 1:1, more preferably 1:0.8, 1:0.5, 1:0.4, or even more preferably 1:0.3. In the context of the present invention, a number is to be interpreted as having been rounded to the last indicated decimal place. For example, the number 0.3 covers the range 0.25-0.34. Similarly, as an additional example, the number 1 covers the range 0.5-1.4.The surfactant, which may be an additional excipient in the composition, may be selected from the group consisting of Tween 20, Tween 80, Span 20 (sorbitan monolaurate), Span 40 (sorbitan monopalmitate), Span 60 (sorbitan monostearate), Span 65 (sorbitan tristearate), Span 80 (sorbitan monooleate), Span 85 (sorbitan trioleate), sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), sodium lauryl sulfate, Triton X-100, lecithin, polyoxyethylene-polyoxypropylene copolymers (Pluronics, for example, Pluronic F-68, Pluronic F-127, or Pluronic L-44), or mixtures. “Tween 20” is a common trade name for a The surfactant known as polysorbate 20 is a non-ionic surfactant belonging to the polyoxyethylsorbitan fatty acid ester family. Polysorbate 20 is created by ethoxylating sorbitan monolaurate, meaning it has multiple ethylene oxide (EO) units added to its structure.The number "20" in "Tween 20" represents the approximate number of ethylene oxide units in the molecule. "Tween 80" is another common trade name for a surfactant known as polysorbate 80. Like polysorbate 20 (Tween 20), polysorbate 80 is a nonionic surfactant that belongs to the polyoxyethylsorbitan fatty acid ester family. Polysorbate 80 is created by ethoxylating sorbitan monooleate, meaning it has multiple ethylene oxide (EO) units added to its structure. The number "80" in "Tween 80" represents the approximate number of ethylene oxide units in the molecule, indicating a higher degree of ethoxylation compared to Tween 20. "Triton X-100" is the specific trade name for a nonionic surfactant known as octylphenol ethoxylate, which belongs to the family of alkylphenol ethoxylated surfactants.In the case of a dispersion composition, in addition to comprising grape extract as the active ingredient, the composition comprises a dispersing agent as an excipient, preferably one or more biodegradable polymers. In one particular embodiment, the biodegradable polymer is a carboxymethylcellulose, such as those commercially available from Lubrizol Corporation of Wickliffe, Ohio, under the trade name Carbopol®. In one particular embodiment, the biodegradable polymer is selected from Carbopol, carboxymethylcellulose, and mixtures thereof.The Carbopol® polymers that may be present in the composition of the present invention include, among others, Carbopol® 974P NF, as homopolymers of type A, type B and / or type C; Carbopol® Ultrez 10, 20, 21 NF; Carbopol® 971P NF; Carbopol® 980 homopolymer type C, Carbopol® 980 NF, Carbopol® 980P, Carbopol® ETD 2020 NF, Carbopol® 71 G NF, Carbopol® 981P NF, Carbopol® 970P NF, Carbopol® 981P NF, Carbopol® 5984P NF, Carbopol® 934P NF, Carbopol® 940P NF, Carbopol® 941P NF, Carbopol® 13242 NF, Carbopol® AA-1 USP NF, Carbopol® TR1 NF and / or Carbopol® TR2 NF. Preferably, the polymer is Carbopol® 974PNF. In one particular embodiment, the composition is a dispersion and comprises from 0.5 to 5% of a biodegradable polymer, preferably as described in the preceding paragraph. Preferably the composition comprises from 1 to 4% of said polymer, more preferably from 1 to 3%, even more preferably from 1 to 2.5%.The pH of the composition of the invention must be compatible with injection. In a preferred embodiment, the pH is between 4 and 8, preferably between 5 and 7, and more preferably between 5.5 and 6.5. The composition of the invention is stable for at least 6 months, and preferably for at least 12 months. "Stable composition" means that the active ingredient and the excipients do not undergo significant degradation and the therapeutic effect is maintained at least at 90% of the effect at the time of preparation of the composition. In a particular embodiment, the pharmaceutical composition may comprise an additional active ingredient not obtained from grape extract. In a particular embodiment, the pharmaceutical composition comprises an antibiotic selected from the group consisting of amoxicillin, benzylpenicillin, cephalexin, cefquinone, enrofloxacin, erythromycin, marbofloxacin, oxytetracycline, penetamate, and mixtures thereof.In a preferred embodiment, the pharmaceutical composition does not comprise an antibiotic selected from the group consisting of amoxicillin, benzylpenicillin, cephalexin, cefquinone, enrofloxacin, erythromycin, marbofloxacin, oxytetracycline, penetamate, and mixtures. In a more preferred embodiment, the pharmaceutical composition does not comprise an antibiotic. In a particular embodiment, the pharmaceutical composition is a veterinary pharmaceutical composition. The pharmaceutical composition can be applied to all non-human milk-producing mammals requiring treatment or prevention of mastitis. In a particular embodiment, the non-human mammal is a dairy animal. In the context of the present invention, "dairy animal" refers to any animal capable of producing milk. Thus, in a particular embodiment, the pharmaceutical composition is for administration to a non-human mammal, preferably cows, camels, buffalo, goats, or sheep.More preferably, the non-human mammal is selected from the group consisting of cows, buffalo, goats, or sheep, even more preferably cows and buffalo, and most preferably cows. In a preferred embodiment, the composition of the invention further comprises water. That is, it comprises water to achieve the desired final volume of the composition. The water in the composition of the invention is preferably water for injection, such as distilled and / or sterile water for injection. The term "water for injection" refers to purified water suitable for intramammary administration; such as water that meets the requirements of the USP (or foreign equivalent) for water for injection. The composition of the invention may comprise additional pharmaceutically acceptable vehicles or excipients.Pharmaceutically acceptable excipients or vehicles include, but are not limited to, preservatives (including antimicrobial and chemical preservatives), tonicity agents, buffering agents, antioxidants, chelating agents, bulking agents, solubilizing agents, surfactants, co-solvents, and combinations thereof. Suitable pharmaceutical vehicles or excipients are described, for example, in A. Adejare's "Remington's Pharmaceutical Sciences," 23rd edition, 2021. Preservatives may include benzalkonium chloride, benzethonium chloride, benzyl alcohol, benzoic acid, chlorobutanol, m-cresol, methylparaben, propylparaben, butylparaben, phenol, 2-phenoxyethanol, phenylmercuric nitrate, phenylmercuric acetate, phenylmercuric borate, thimerosal, and mixtures thereof.The tonic agents typically used are sodium chloride, dextrose, glycerol, glycerin, mannitol, potassium chloride, propylene glycol, and mixtures thereof. Buffering agents may include sodium / potassium citrate and / or phosphate buffer, acetic acid / glacial acetic acid / ammonium acetate, sodium hydroxide, tris acetate, ammonium sulfate, ammonium hydroxide, arginine, benzenesulfonic acid, sodium benzoate, sodium bicarbonate, boric acid, sodium carbonate, carbon dioxide, diethanolamine, glucono delta lactone, glycine / glycine HCl, histidine / histidine HCl, hydrochloric acid, hydrobromic acid, lysine, maleic acid, methanesulfonic acid, monoethanolamine, sodium / disodium succinate, sulfuric acid, sodium tartrate / acid, and mixtures thereof.Antioxidants may include ascorbic acid, acetylcysteine, ascorbyl palmitate, sodium ascorbate, butylated hydroxytoluene, butylhydroxyanisole, citric acid, monothioglycerol, sulfurous acid salts (bisulfite, metabisulfite), methionine, sodium metabisulfite, potassium metabisulfite, acetone metabisulfite, cysteine ​​hydrochloride, sodium dithionite, gentisic acid, sodium glutamate, glutathione, thioglycerol, propyl gallate, sodium sulfite, sodium bisulfite, sodium formaldehyde sulfoxylate, thiourea, alpha tocopherol, and mixtures thereof. Chelating agents may include disodium edetate, sodium edetate, disodium calcium edetate, DTPA, citric acid monohydrate, calcium versetamide, calteridol, ethylenediaminetetraacetic acid, and mixtures thereof. Bulking agents may include mannitol, sucrose, lactose, dextran, trehalose, sorbitol, glucose, raffinose, glycine, histidine, and mixtures thereof.The solubilizing and co-solvent agents may include alcohols such as ethanol, benzyl benzoate, dimethylacetamide, glycerin, sorbitol, polyethylene glycol, pyrrolidone, and propylene glycol. In one embodiment, the pharmaceutical composition of the invention may comprise additional pharmaceutically acceptable vehicles or excipients in an amount of 0 to 50% w / v, 0 to 40% w / v, or even 0 to 30% w / v. That is, the composition may not include additional pharmaceutically acceptable vehicles or excipients (0% w / v) or may include additional pharmaceutically acceptable vehicles or excipients in a maximum amount of 50% w / v, 40% w / v, or 30% w / v, respectively. In a particular embodiment, the pharmaceutical composition of the invention may comprise additional pharmaceutically acceptable vehicles or excipients in an amount of 0 to 20% w / v, or even 0 to 10% w / v.The term "pharmaceutically acceptable excipient" refers to a vehicle, diluent, or adjuvant administered with the active ingredient. A fifth aspect of the present invention relates to an intramammary syringe comprising the pharmaceutical composition of the invention. In one particular embodiment, the intramammary syringe of the fifth aspect comprises a biodegradable carboxypolymethylene polymer, Carbopol®. In one particular embodiment, the intramammary syringe comprises 0.5 to 5% of a biodegradable polymer, preferably selected from the polymers described in aspect four of the invention. Preferably, the intramammary syringe comprises 1 to 4% of said polymer, more preferably 1 to 3%, and even more preferably 1 to 2.5%.Therapeutic Indication: A sixth aspect of the present invention relates to a pharmaceutical composition for use in the treatment and / or prevention of mastitis in a non-human mammal, characterized in that it is a composition for intramammary administration comprising a white grape extract as the active ingredient. In a preferred embodiment, said extract is the white grape extract of the invention, or the white grape extract obtainable according to the method of the invention. In a particular embodiment, the pharmaceutical composition for use according to the sixth aspect comprises a biodegradable carboxypolymethylene polymer, Carbopol®. In a particular embodiment, the pharmaceutical composition for use according to the sixth aspect comprises from 0.5 to 5% of a biodegradable polymer, preferably selected from the polymers described in aspect four of the invention.Preferably, the pharmaceutical composition for use according to the sixth aspect comprises from 1 to 4% of said polymer, more preferably from 1 to 3%, and even more preferably from 1 to 2.5%. The term "treatment" or "treat" means the administration of a composition according to the invention to improve or eliminate the disease or one or more symptoms associated with said disease. "Treatment" also encompasses improving or eliminating the physiological sequelae of the disease. In a particular embodiment, the mastitis to be treated is selected from clinical or subclinical mastitis, preferably clinical mastitis. The term "improve" in the context of this invention means any improvement in the condition of the treated mammal. The term "prevention" or "prevent" means the administration of a composition according to the invention to reduce the risk of acquiring or developing the disease or one or more symptoms associated with said disease.In one particular embodiment, the disease to be prevented is clinical or subclinical mastitis, preferably subclinical. Prevention also includes the treatment of non-human mammalian animals, for example, cows, that do not exhibit any signs of mastitis but are in the presence of other animals that have at least one sign of mastitis, in order to minimize or prevent the transmission or potential transmission of mastitis from one animal to another. Alternative definitions of the sixth aspect of the invention are: A method for the treatment and / or prevention of mastitis in a non-human mammal, characterized in that the method comprises administering to a subject requiring such treatment and / or prevention a therapeutically effective amount of a pharmaceutical composition for intramammary administration comprising a white grape extract.Use of a pharmaceutical composition for intramammary administration comprising a white grape extract, for the manufacture of a medicament for the treatment and / or prevention of mastitis in a non-human mammal. The term "therapeutically effective amount" means the amount of composition which, when administered, delivers a quantity of one or more pharmaceutically active agents contained therein to provide a therapeutic benefit in the treatment or management of a disease or condition. Treatment of mastitis is the cure or improvement of an animal with contracted mastitis, i.e., the reduction of at least one symptom of mastitis. Mastitis refers to inflammation of the mammary gland. It is characterized by physical, chemical, and usually bacteriological changes in the milk and pathological changes in the glandular tissue.Glandular changes often result in a range of symptoms, such as milk discoloration, the presence of clots, and high white blood cell counts. Clinically, mastitis presents as swelling, heat, pain, and induration of the mammary gland, often leading to udder deformity. An inflamed udder can be visibly observed or detected by palpation. In many cases, the diagnosis of subclinical infections has come to rely heavily on indirect tests based on the milk's white blood cell content (flakes, clots, or serous milk), the detection of at least one bacterium in at least 100 µL of milk from the udder, an elevated somatic cell count (SCC), usually greater than 300,000 cells / mL, and / or increased electrical conductivity of the milk.In one particular embodiment, mastitis treatment is considered to occur when the elevated somatic cell count (SCC) is less than 300,000 cells / mL, preferably less than 200,000 cells / mL, and more preferably less than 100,000 cells / mL. The injectable mastitis composition of the present invention can be used as a therapeutic agent to improve mastitis to a normal state and / or as a preventive agent to suppress the occurrence of mastitis. In the present invention, "mastitis" includes both clinical and subclinical mastitis. Clinical mastitis has macroscopic abnormalities such as red swelling, fever, pain, or clumps in the milk, while subclinical mastitis can occur in the mammary gland without such abnormalities. Examples of bacteria that cause mastitis are Escherichia coli, Klebsiella spp., Enterobacter spp., Salmonella spp., Citrobacter spp., Serratia spp., Shigella spp., Edwardsiella spp., Hafnia spp., Morganella spp.Providencia spp., Yersinia spp., Staphylococcus aureus, Staphylococcus spp., Pseudomonas spp., Streptococcus uberis (S. uberis), Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus spp., Enterococci, Corynebacterium spp., Arcanobacterium spp., Actinomyces spp., Mycobacterium spp., Prototheca spp., Mycoplasma spp., and Erwinia spp. In one particular embodiment, the injectable composition is an antibacterial composition against Gram-positive bacteria. A person skilled in the art will be able to determine the optimal time of administration. For example, the composition of the invention can be administered during lactation, and since the extract can be allowed to act on the breast for an extended period, it can also be administered during periods when milking is not taking place. The frequency of administration can also be determined according to the needs of each individual case.In one particular embodiment, the composition is administered at least once a day (daily), at least once every two days, or at least once a week. In one particular embodiment, the administered dose of the veterinary pharmaceutical composition of the invention is between 0.002 mL and 0.030 mL of the pharmaceutical composition per kg of animal weight. Preferably, the dose is between 0.006 mL and 0.019 mL, more preferably between 0.008 mL and 0.016 mL, and even more preferably between 0.009 mL and 0.014 mL per kg of animal weight. In another particular embodiment, the administered dose of the veterinary pharmaceutical composition of the invention comprises between 0.0004 g and 0.0288 g of the grape extract (dry weight) per kg of animal weight. Preferably, the dose is 0.0011 to 0.0182 g, more preferably 0.0016 to 0.0154 g, even more preferably 0.0018 to 0.0134 g per kg of animal weight.In the field of mastitis treatment in animals, several routes of administration have been employed, each with its own advantages and considerations. The pharmaceutical composition of the present invention is formulated as an injectable composition for intramammary injection. In the context of the present invention, “intramammary injection” includes “udder infusion.” Udder infusion involves the direct injection of drugs into the affected region of the udder through the teat. The primary objective is to achieve localized administration and precision therapy. The efficacy of udder infusion lies in its ability to deliver treatment directly to the site of infection, minimizing systemic exposure. A seventh aspect of the present invention relates to the extract of the invention, or the extract obtainable according to the process of the invention, for use in the treatment and / or prevention of mastitis in a non-human mammal.Alternative definitions of the seventh aspect of the invention are: A method for the treatment and / or prevention of mastitis in a non-human mammal, characterized in that the method comprises administering to a subject requiring such treatment and / or prevention a therapeutically effective quantity of the extract of the invention, or of the extract obtainable according to the process of the invention. Use of the extract of the invention, or of the extract obtainable according to the process of the invention, for the manufacture of a medicament for the treatment and / or prevention of mastitis in a non-human mammal. Experimental Part. These examples serve to illustrate embodiments of the invention, but in no case should they be considered limiting. Analysis of the extracts. The extracts selected as active ingredients for the intramammary veterinary compositions of the invention were obtained in two ways. On the one hand, a solvent mixture consisting of an isovolumetric mixture of propylene glycol and water (50 / 50) was used. On the other hand, acetone was used as a solvent, and the resulting liquid extract was subjected to an acetone volatilization process to obtain an aqueous extract. Using sand as a dispersant, it was mixed and ground with Albariño white grape pomace in a 1:5 ratio. This mixture was introduced into a stainless steel column of appropriate dimensions with a layer of dispersant at the bottom, which acts as a filter, and was lightly compacted.The amount of solvent used as the extraction solvent was 0.75 volumes relative to the volume of the extractive mixture when acetone was used, and 0.625 volumes when the isovolumetric mixture of propylene glycol and water was used. After 48 h of maceration, the corresponding eluate was obtained. Subsequently, when the extraction solvent was acetone, this eluate was concentrated under vacuum until a residual acetone value of less than 0.5% was reached. Example 2. Analytical Characterization Total Polyphenol Index (TPI) The total polyphenol content of several white grape pomace extracts obtained according to the method described in Example 1 was determined using the Folin-Ciocalteu method following the protocol for microtiteration in 96-well plates adapted from Zhang et al. (Zhang Q, Zhang J, Shen J, Silva A, Dennis DA, Barrow CJ. A simple 96-well microplate method for estimation of total polyphenol content in seaweeds. J Appl Phycol.(2006) 18:445–50). Thus, 20 µL of diluted extract were mixed with 100 µL of Folin-C1ocalteu reagent (1:10) and 80 µL of a sodium carbonate solution (7.5% w / w). The mixture was stirred in the dark for 30 minutes and then measured at 760 nm using a SPECTROstar Nano microplate reader (BMG LABTECH, Ortenberg, Germany), which performs absorbance measurements in the 220–1000 nm wavelength range. Measurements were performed on 96-well polypropylene microplates with a volume of 300 µL. Gallic acid was used as a standard to express the total polyphenol index, with a concentration range of 12 levels between 30 and 200 mg / L (0.2–0.8 AU). The total polyphenol content of the samples is thus expressed as milligrams of gallic acid equivalents per liter of extract (mgGAE / L).For the extracts obtained using acetone as a solvent, the analysis was performed, and the IPT range obtained was between 7000 and 10000 mgGAE / L for the non-volatilized extracts (12 samples, average of 8699 mgGAE / L), and between 11000 and 43000 mgGAE / L for the volatilized extracts (33 samples, average of 27866 mgGAE / L). For the non-volatilized extracts obtained using a propylene glycol:water (50:50) mixture as a solvent, the analysis was performed, and the IPT range obtained was between 1000 and 8500 mgGAE / L (15 samples, average of 6287 mgGAE / L). Identification of target polyphenols by Liquid Chromatography coupled to tandem mass spectrometry (LC-MS / MS)The extracts obtained according to Example 1 were filtered through 0.22 µm PTFE syringe filters onto a 2 mL glass vial for the corresponding analyses.The main polyphenols present in the extracts of Example 1 were identified by liquid chromatography coupled to tandem mass spectrometry, triple quadrupole (LC-MS / MS_QqQ). The optimal instrumental conditions for the detection of the target polyphenols were adapted from Celeiro, M.; Lamas, JP; Arcas, R.; Lores, M. Antioxidants Profiling of By-Products from Eucalyptus Greenboards Manufacture, Antioxidants.2019, 8(8), 263. The LC-MS / MS analysis was performed using a Thermo Scientific instrument (San Jose, CA, USA) based on a TSQ Quantum UltraTM triple quadrupole mass spectrometer equipped with a HESI-II (heated electrospray ionization) source and an Accela Open autosampler with a 20 μL loop. Chromatographic separation was achieved on a Kinetex C18 column (2.6 μm, 100 × 2.1 mm) with a pre-column (SecurityGuardTM ULTRA Holder) obtained from Phenomenex (Torrance, CA, USA).The injection volume was 10 μL and the column temperature was set at 50 °C. The mobile phase consisted of water (A) and methanol (B), both containing 0.1% formic acid. The chromatographic gradient was from 5% B to 90% B in 11 min and was held constant for 3 min. Initial conditions were reached in 6 min. The mobile phase flow rate was 200 μL / min. -1The total run time for each injection was 20 min. The mass spectrometer and the HESI-II source operated simultaneously in positive and negative modes (see the ionization mode for each target compound in Table 1). Selected Reaction Monitoring (SRM) acquisition mode was implemented, monitoring 2 or 3 transitions per compound (see Table 1) for unambiguous identification of the target compounds. The system was managed using the Xcalibur 2.2 and Trace Finder™ 3.2 software programs. Table 1. Compounds studied by chromatography. Ionization mode, CAS number, retention time, and MS / MS transitions. Ionization Mode Time MS / MS Transitions Retention (min) (Collision energy, eV) -Gallic acid 149-91-7 2.25169.02 → 125.04 (17) 169.02 → 153.1 (15) 2-4-6-trihydrobenzoic acid 168.98 → 150.99 (17) 487-70-7 3.23168.98 → 83.02 (23) 168.98 → 107.02 (22) -Caftaric acid 67879-58-7 4.21310.96→ 178.97 (17) 310.96 → 148.96 (14) 577.03 → 407.06 (26) -Procyanidin B1 20315-25-7 4.76577.03 → 288.93 (25) 577.03 → 424.97 (26) +Catechin 225937-10-0 5.02289.00 → 245.02 (17) 289.00 → 203.11 (22) 577.03 → 407.06 (26) -Procyanidin B2 29106-49-8 5.50577.03 → 288.93 (25) 577.03 → 424.97 (26) 457.15 → 169.05 ( + Gallate of 21) epigallocatechin989-51-5 6.00457.15 → 125.09 (42) 457.15 → 305.09 (21) 577.03 → 288.93 (25) -Procyanidin C1 37064-30-5 6.01577.03 → 407.06 (26) 577.03 → 424.97 (26) +Epicatechin 490-46-0 6.11289.00 → 245.02 (17) 289.00 → 203.11 (22) Gala 441.13 → 289.13 (30) + to of epicatechin1257-08-5 7.13441.13 → 125.08 (42) 441.13 → 169.05 (24) + Quercetin-3-22688-79-5 9.21479.09 → 461.50 (14) → -Kaempferol 520-18-3 12.27285.07 → 184.91 (30) 285.07 → 239.12 (35) The main polyphenols present in the extracts were determined by liquid chromatography coupled to tandem mass spectrometry, triple quadrupole (LC-MS / MS_QqQ) using the method described above. The results are shown in Table 2. Table 2. Ranges of polyphenols present in white grape extracts obtained after extraction with a 50 / 50 mixture of propylene glycol / water (14 extracts) or acetone (12 extracts). Values ​​expressed in ppm (mg / L). Polyphenols Propylene glycol extract Water Acetone extract Gallic acid 10-40 8-30 2,4-6-Trihydrobenzoic acid 1-3 1-30 Caftaric acid 4-7 0.1-4 Procyanidins B1+B2+C1 60-130 100-280 Catechin 50-70 60-130 Epigallocatechin gallate 0.1-3 0.1-1.2 Epicatechin 50-70 10-150 Epicatechin gallate 3-20 15-50 Quercetin-3-glucuronide 10-25 30-65 Quercetin-3-rutinoside 0.2-1 2-5 Quercetin-3-glucoside 10-25 30-120 Kaempferol 0.1-3 0.1-2.5Quercetin 1-5 0.1-15Example 3.Antibacterial activity of the extracts. In vitro antimicrobial assays have been performed to evaluate the antimicrobial activity of the polyphenolic extracts of the invention. Methodology: The antimicrobial tests were performed according to EUCAST recommendations, using the Alamar-Blue colorimetric / fluorometric method and reading the plates by fluorometry. The methodology involves incubating the cells in Müller-Hinton broth supplemented with different concentrations (ranging from 0.625 to 20%) of the antimicrobial substance to be evaluated and the appropriate amount of resazurin. This non-fluorescent molecule is converted to the fluorescent molecule resorufin in the presence of metabolically active cells. This reaction allows the number of live cells to be quantified by measuring the fluorescence released by the resorufin produced during the process.This protocol provides Minimum Bactericidal Concentrations (MBC) values, so the Minimum Inhibitory Concentration (MIC) is calculated as the average between the MBC and the immediately preceding concentration tested. IC50 values ​​(the extract concentration that inhibits the growth of half an inoculum of the tested bacteria) were obtained using the IC50 calculator program (AAT Bioquest). The microorganisms tested included Gram-positive bacterial strains, with Staphylococcus aureus ATCC 25923 as the reference strain and Streptococcus uberis ATCC19436 as the main target microorganism, since mastitis is caused, among other things, by this bacterium, which invades mammary tissue causing inflammation of the mammary gland. Results: The results of the antimicrobial effect of the extracts, evaluated in triplicate assays, are shown in Table 3.Table 3 shows the antimicrobial activity of comparative extracts obtained with ethyl lactate and ethanol. Table 3. Antimicrobial activity of the different extracts against S. aureus and S. uberis strains. IC50 is the extract concentration responsible for 50% bacterial inhibition. IC50 (%) is the percentage dilution of the extract responsible for 50% bacterial inhibition. MIC (minimum inhibitory concentration) is the lowest extract concentration that inhibits bacterial growth after incubation. MIC (%) is the percentage dilution of the lowest extract that inhibits bacterial growth after incubation. S. aureus (Gram +) extractuberis (Gram +) IC50 (%) MIC (%) IC50 (%) MIC (%) Propylene glycol / water 1.79 < 5 7.5 < 10 Acetone 0.33 < 0.625 1.88 < 2.5 Ethyl lactate / water 0.9 1.03 2.65 3.75 Ethanol / water 1.07 >20 -- --The propylene glycol / water and acetone extracts have the capacity to inhibit microbial growth (MIC). The solvents are compatible with the route of administration. In addition, the acetone extract possesses surprising antimicrobial activity. In the case of the comparative extract obtained with ethyl lactate, using almost 50% ethyl lactate for intramammary administration would cause irritation and inflammation in the mammary gland. The lethal dose 50 (LD50) of ethyl lactate administered parenterally (subcutaneously) is 2.5 g / kg, while for propylene glycol it is 17.37 g / kg. Example 4. Preparation of intramammary formulations. Paraffin oil-in-water emulsion loaded with propylene glycol:water extract.A paraffin oil-in-water (O / W) emulsion was developed using paraffin oil as the oil phase and a 1:1 propylene glycol:water (PG:W) extract as the aqueous phase in a 1:0.3 ratio. Tween 80 at 2.5% (v / v) was used as the surfactant. The formulation components and proportions were selected according to the hydrophilic-lipophilic balance (HLB). To prepare 10 mL of the formulation, 2.25 mL of PG:W extract, 7.5 mL of paraffin oil, and 0.25 mL of Tween 80 were used. Both phases (and the surfactant) were mixed using a high-shear homogenizer (Ultra-Turrax, IKA) at 10,000 rpm for 5 minutes. The physicochemical properties of the formulation were characterized to evaluate its stability and performance. The rheological behavior of the formulations, along with pH, ​​emulsion sign, globule size, and miscibility with milk, were evaluated and are described in Table 4.The pH was evaluated using a Hanna Instruments pH meter equipped with a probe for viscous samples (HI1053B). The syringeability of the formulation at room temperature was evaluated using a TA XT Plus Texture Analyzer (Surrey, UK), calculating the work required to expel the loaded formulation into intramammary cannulas. In short, the cannulas were loaded with the formulation, avoiding the formation of air bubbles. They were then placed vertically on a stand, and the texture analyzer plunger was lowered at 2 mm / s, pressing the cannula piston to a distance of 2 cm. All measurements were performed six times. Viscosity was evaluated using an AR1000-N rheometer (TA Instruments, UK). A 6 cm Ø, 2.1° cone-plate geometry was used to record the storage (G') and loss (G'') moduli at an angular frequency of 5 rad / s.The emulsion sign was identified using a Neubauer chamber by staining the oil phase with Sudan III. Globule size and size dispersion were assessed according to the USP method using dynamic light scattering with a Zetasizer Pro (Malvern Instruments, Malvern, UK). Samples were diluted with Milli-Q® water (1:1000), placed in a dedicated cell (DTS 1070), and measured using an automated measurement process. All measurements were performed in triplicate. Miscibility with milk was assessed by observing any phase separation after dilution of the formulations with milk. Sterile formulations were further prepared using two strategies: 1) using sterile formulation components and formulating the systems aseptically in a laminar flow hood, or 2) sterilizing the formulations using a terminal sterilization strategy with gamma radiation at 25 kGy.In both cases, the extract was basified using 10M NaOH until a pH of approximately 7 was reached. For the aseptic formulation, the extract was filtered through a 0.22 µm filter to sterilize it in the same way as the surfactant solution, while the paraffin oil was sterilized by dry heat. The high-shear homogenizer used for mixing was also previously sterilized using ethanol. Table 4 shows the results of the non-sterile formulations and those prepared using both sterilization strategies. Table 4. Physicochemical properties of the paraffin oil emulsion and the propylene glycol:water extract. sterilización -Formulation in Terminal Aseptic Sterilization Syringability (Pa·s) 342.10 ± 14.00 - -Viscosity at 22 °C (Pa·s) 35.00 ± 5.34 21.54 ± 2.64 -pH 4.74 ± 0.02 5.84 ± 0.10 4.56Emulsion Sign O / WO / WO / WGolbule Size (nm) 3660.8 ± 28.6 4387.8 ± 54.7 5223.3 ± 212.6Golbule Size Dispersion (PDI)0.3 ± 0.1 0.2 ± 0.0 0.2 ± 0.1Miscible with Milk YES YES YES. The flow properties of the formulations were analyzed in comparison with two commercial intramammary formulations approved for the treatment of bovine mastitis, commercial formulation 1 (Ilovet-clox®, whose composition per syringe comprises 250 mg of neomycin sulfate and 500 mg of cloxacillin benzathine) and commercial formulation 2 (Mammicurine 800®, for intramammary injection, comprising 0.25 mL Calendula officinalis, 0.25 mL Solanum lycopersicum, 0.04 mL Echinacea, 0.25 mL Phytolacca americana, and 0.10 mL Solidago virgaurea L), using an AR1000-N controlled stress rheometer (TA Instruments,United Kingdom). A frequency sweep between 0.05 and 50 rad / s and an oscillatory stress of 0.1 Pa were used with a cone-plate geometry of 6 cm Ø and 2.1°. The [Error! Reference source not found.] shows similar behavior between the developed and commercially available formulations. The flow properties were very similar to those obtained for the commercial formulations, showing a behavior in which increasing the shear force decreases the viscosity, facilitating the administration of the formulation. The non-sterilized formulations were characterized again at later times (after 1,3 and 6 months) to evaluate their stability. Table 5 shows the results obtained for the non-sterile formulations at different times after storage at 4°C. The formulations were stable for at least six months. Table 5. Physicochemical properties of the paraffin oil emulsion and the propylene glycol:water extract evaluated at different times. Time 1 month 3 months 6 months Viscosity at 22 °C (Pa·s) 34.46 ± 6.37 45.92 ± 16.09 18.59 ± 4.57 pH 4.25 ± 0.03 4.22 ± 0.04 4.75 ± 0.06 Emulsion sign O / WO / WO / W Globule size (nm) 5597.2 ± 938.6 4128.4 ± 722.8 2610.8 ± 758.7 Globule size dispersion (PDI) 0.3 ± 0.1 0.4 ± 0.1 0.2 ± 0.1 Miscible with milk YES YES YES Peanut oil-in-water emulsion loaded with propylene glycol extract:water A peanut oil-in-water emulsion was developed using the hydrophilic-lipophilic balance (HLB). In this case, two surfactants were required: an aqueous surfactant and an oily surfactant.The final components were Tween 80 (4.60% v / v) and Span 65 (15.80% v / v). Peanut oil was the oil phase component, and propylene glycol:water (PG:W) extract was the aqueous phase in a 1:0.3 ratio. To prepare 10 mL of the formulation, 1.84 mL of PG:W extract, 6.12 mL of peanut oil, 0.46 mL of Tween 80, and 1.58 mL of Span 65 were used. Both phases were mixed using a high-shear homogenizer (Ultra-Turrax, IKA) at 10,000 rpm for 5 minutes in an ice bath. The formulation properties were characterized as previously described for the paraffin oil emulsion. Table 6 shows the experimental data obtained. Table 6. Physicochemical properties of the peanut oil emulsion and propylene glycol:water extract. Non-sterile formulation. Syringability (Pa·s) 545.30 ± 72.40 Viscosity at 22 °C 913.90 ± 425.60 (Pa·s) pH 4.60 ± 0.00 Emulsion Sign O / W Miscible with milk YES The formulations were not stable for more than one month when stored at 4°C. Polymer dispersion loaded with propylene glycol:water extract Different polymer dispersions prepared using propylene glycol:water extract were tested for mastitis management. For the preparation of 10 mL of formulation, 9.6 mL of PG:W extract and 0.4 g of Carbopol 974. The polymer dispersion was obtained by adding the polymer to the extract followed by homogenization using a Silverson L4R. The formulation was fully characterized as described for the previous examples, and the experimental data obtained are shown in Table 7. Sterile formulations were also prepared using two strategies: 1) using the components of the sterile formulations and formulating the systems aseptically using a laminar flow hood, or 2) sterilizing the formulations using a terminal sterilization strategy with gamma radiation at 25 kGy. In this case, the polymer dispersions were basified using 10 M NaOH prior to radiation. For the aseptic formulation, the extract was filtered through a 0.22 µm filter for sterilization.The polymer was sterilized by UV radiation in the laminar flow hood. The high-shear homogenizer used for mixing was also previously sterilized using 70% ethanol. Table 7 shows the results of the non-sterile formulations or those following both sterilization strategies. Table 7. Physicochemical properties of the Carbopol 4% polymer dispersions containing propylene glycol:water. E, sterilización -Formulation in Terminal Aseptic Sterilization Syringability (Pa·s) 348.90 ± 26.20 - -Viscosity at 22 °C34.30 ± 7.10 34.28 ± 6.07 -(Pa·s) pH 3.84 ± 0.02 3.68 ± 0.01 6.20 ± 0.16Miscible with milk YES YES YESThe flow properties of the formulations were analyzed in comparison with two commercial intramammary formulations approved for the treatment of bovine mastitis (commercial formulation 1 and 2) as described above. The flow properties were very similar to those obtained for the commercial formulations, showing a behavior in which increasing the shear force decreases the viscosity, facilitating the administration of the formulation (graph omitted as it is similar to Figure 1). The non-sterile formulations were characterized again at later times (after 1, 3 and 6 months) to evaluate their stability.Table 8 shows the results obtained for the non-sterile formulations at different times after storage at 4°C. The polymer dispersions were stable for at least six months. Table 8. Physicochemical properties of the Carbopol 4% polymer dispersions and the propylene glycol:water extract evaluated at different times. Time 1 month 3 months 6 months Viscosity at 22 °C 39.01 ± 12.38 42.03 ± 13.53 14.89 ± 1.95 (Pa·s) pH 3.34 ± 0.09 3.29 ± 0.05 3.97 ± 0.07 Miscible with milk YES YES YES Polymeric dispersions were prepared with additional Carbopol 974, this time at 2% and 1% w / v containing the propylene glycol:water extract. To prepare 10 mL of a 2% formulation, 9.8 mL of propylene glycol:water extract and 0.2 g of Carbopol 974 were used. To prepare 10 mL of a 1% formulation, 9.9 mL of propylene glycol:water extract and 0.1 g of Carbopol 974 were used.The dispersions were obtained following the same process described above. These formulations were subjected to terminal sterilization by gamma radiation at 25 kGy. The dispersions were basified using 10 M NaOH prior to irradiation. The resulting formulations were found to be equally miscible with milk, and the viscosity at 22 °C (Pa·s) was 42.21 ± 3.16 and 14.98 ± 1.75 for the propylene glycol extract:water and Carbopol formulations at 2% and 1%, respectively. Paraffin oil in water emulsion loaded with volatilized acetone extract. A paraffin oil in water (O / W) emulsion was developed using paraffin oil as the oil phase and acetone extract (AC), after solvent evaporation, as the aqueous phase in a ratio of 1:0.3. Evaporation of the acetone after extraction resulted in an aqueous dispersion.The extract was basified using 10M NaOH to reach a pH of approximately 7. It was filtered through a 0.22 µm filter for sterilization, as was the surfactant solution, while the paraffin oil was sterilized by dry heat. Tween 80 at 2.5% (v / v) was used as the surfactant for emulsification, and the formulation components were selected according to the hydrophilic-lipophilic balance (HLB). To prepare 10 mL of formulation, 2.25 mL of AC extract, 7.5 mL of paraffin oil, and 0.25 mL of Tween 80 were used. Both phases were mixed in a laminar flow hood using a high-shear homogenizer (Ultra-Turrax, IKA), previously sterilized with ethanol, at 10,000 rpm for 5 minutes. These aseptically prepared formulations were characterized in terms of physicochemical properties as mentioned above.Alternatively, formulations with the same composition were prepared, but without undergoing the prior sterilization of the materials. In these cases, the formulations underwent terminal sterilization by gamma radiation with a dose of 25 kGy. The properties of the formulations sterilized by both strategies are described in Table 9. Table 9. Physicochemical properties of the paraffin oil emulsion and the volatilized acetone extract.Sterilization Formulation in Terminal Aseptic Sterilization Viscosity at 22 °C 2 - (Pa·s) 8.15 ± 0.85 pH 6.27 ± 0.02 4.18 Emulsion sign O / WO / W Globule size (nm) 3643.3 ± 721.7 1982.5 ± 715.5 Globule size dispersion (PDI) 0.2 ± 0.0 0.7 ± 0.3 Miscible with milk YES YES The flow properties of the formulations were analyzed in comparison with two commercial intramammary formulations approved for the treatment of bovine mastitis (commercial formulation 1 and 2) as described above. The flow properties were very similar to those obtained for commercial formulations, showing a behavior in which increasing the shear force decreases the viscosity, facilitating the administration of the formulation (graph omitted because it is similar to Figure 1).Polymer dispersion loaded with volatilized acetone extract. Intramammary syringes of the polymer dispersion type were developed using 4% (w / v) Carbopol 974 as a base. To prepare 10 mL of formulation, 9.6 mL of AC extract and 0.4 g of Carbopol 974 were used. The polymer dispersion was obtained by adding the polymer, previously sterilized by UV radiation, to the extract, which had been previously sterilized through 0.22 µm filters, followed by homogenization in a laminar flow hood. These aseptically prepared formulations were characterized in terms of physicochemical properties as previously mentioned. Alternatively, formulations with the same composition were prepared, but without undergoing the prior sterilization of the materials. In these cases, the formulations underwent terminal sterilization by gamma radiation at 25 kGy.In this case, the polymer dispersions were basified using 10M NaOH prior to irradiation. The properties of the formulations sterilized by both strategies are described in Table 10. Table 10. Physicochemical properties of the polymer dispersions containing the volatilized acetone extract. Sterilization Formulation in Terminal aseptic sterilization Viscosity at 22 °C. 13,36 ± 1,10 23,86(Pa·s) pH 3.40 ± 0.13 5.70 ± 0.36 Miscible with milk YES YES The flow properties of the formulations were analyzed in comparison with two commercial intramammary formulations approved for the treatment of bovine mastitis (commercial formulations 1 and 2) as described above. The flow properties were very similar to those obtained for the commercial formulations, showing a behavior in which increasing the shear force decreases the viscosity, facilitating the administration of the formulation (graph omitted as it is similar to Figure 1). The polymer dispersion remained stable for three months at 4°C. Additional polymer dispersions were prepared with Carbopol 974, this time at 2% and 1% w / v containing the acetone extract. To prepare 10 mL of a 2% formulation, 9.8 mL of acetone extract and 0.2 g of Carbopol 974 were used.To prepare 10 mL of a 1% formulation, 9.9 mL of acetone extract and 0.1 g of Carbopol 974 were used. The dispersions were obtained following the same process described above. These formulations were subjected to terminal sterilization by gamma radiation at 25 kGy. The dispersions were basified using 10 M NaOH prior to irradiation. The formulations obtained were found to be equally miscible with milk, and the viscosity at 22 °C (Pa·s) was 54.49 ± 0.33 and 4.35 ± 1.38 for the acetone extract and Carbopol formulations at 2% and 1%, respectively. Example 5. Antimicrobial activity of the intramammary formulations comprising the extracts. In vitro antimicrobial assays were performed to evaluate the antimicrobial activity of the formulations described in Example 4, comprising the polyphenolic extracts of the invention. The experimental protocol was that described in Example 3.The results of the antimicrobial effect of the formulations, evaluated in triplicate assays, are shown in Table 11. Table 11. Antimicrobial activity of the formulations described above sterilized by gamma radiation against the S. aureus and S. uberis strains. IC50 is the extract concentration responsible for 50% bacterial inhibition. IC50 (%) is the percentage dilution of the extract responsible for 50% bacterial inhibition. MIC (minimum inhibitory concentration) is the lowest extract concentration that inhibits bacterial growth after incubation. Similarly, MIC (%) is the percentage dilution of the lowest extract that inhibits bacterial growth after incubation. n / a refers to not applicable since the number of viable cells exceeded 50%. Formulation S. aureus (Gram +) S.uberis (Gram +)IC50 (%) MIC (%) IC50 (%) MIC (%) Paraffin oil emulsion in water loaded with the extract den / a > 55.56 n / a > 55.56propylene glycol:water Propylene glycol extract dispersion:water y2.70 ≤ 20 1.94 > 20Carbopol 974 at 4% (w / v) Paraffin oil emulsion in water loaded with the extract of acetone an / a > 55.56 n / a > 55.56volatilized Dispersion of volatilized acetone extract y< 0.625 ≤ 0.625 0.71 ≤ 1.25Carbopol 974 at 4% (w / v) 6. Further characterization of the extracts according to the invention and of extracts. The model profile of the volatilized acetone extract (AC) obtained according to the invention was analyzed using UHPLC-QTOF (Ultra-High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry), which has enabled the precise characterization of the compounds present in the extracts, allowing detailed information to be obtained about their chemical profile, including the determination of molecular structures, exact masses and possible fragmentations. The same analysis was performed for the extracts according to the invention obtained with propylene glycol / water, and also for comparative extracts obtained with ethyl lactate / water and ethanol / water. Table 12. Compositional profile obtained by targeted UHPLC-QTOF analysis of the extracts acetone (AC), Ethyl Lactate:water (EL:W), Ethanol:water 50:50 (ET50V), Evaporated Ethanol (ET100V) and Propylene Glycol:water (PG:W). Values ​​expressed in ppm (mg / L).Propylene glycol extract Acetone extract Ethyl lactate extract EtOH / water Organic acids Citric acid 139.95 14.0 25.34 11.27 Quinic acid 0.92 0.17 0.09 0.11 Malic acid 201 122 92 81 Ascorbic acid 1.004 0.837 0.922 0.855 Maleic acid 224 180 141 130 Succinic acid 3.2 24.6 16.2 23.0 Azelaic acid - 0.212 - 0.059 Sugars Glucose 2215 1818 1301 1798 Sucrose 2.42 5.88 7.98 3.63Sorbitol 9.7 10 4.1 3.7Essential fatty acidsLinoleic acid - - 6.39 0.49Linolenic acid - - 3.09 -.

Claims

CLAIMS 1. White grape extract, characterized in that it comprises gallic acid, 2,4,6-trihydrobenzoic acid, caftaric acid, procyanidin B1, procyanidin B2, procyanidin C1, catechin, epigallocatechin gallate, epicatechin, epicatechin gallate, quercetin-3-glucuronide, quercetin-3-rutinoside, quercetin-3-glucoside, kaempferol and quercetin.

2. Extract according to claim 1, characterized in that it comprises: - a gallic acid concentration of between 10 and 40 mg / L of extract; - a 2,4,6-trihydrobenzoic acid concentration of between 1 and 5 mg / L of extract; - a caftaric acid concentration of between 4 and 7 mg / L of extract; - a procyanidin B1+B2+C1 concentration of between 60 and 130 mg / L of extract; - a catechin concentration of between 50 and 70 mg / L of extract; - an epigallocatechin gallate concentration of between 0.1 and 3.0 mg / L of extract; - an epicatechin concentration of between 50 and 70 mg / L of extract;- an epicatechin gallate concentration of between 3 and 20 mg / L of extract; - a quercetin-3-glucuronide concentration of between 10 and 25 mg / L of extract; - a quercetin-3-rutinoside concentration of between 0.2 and 1.0 mg / L of extract; - a quercetin-3-glucoside concentration of between 10 and 25 mg / L of extract; - a kaempferol concentration of between 0.1 and 3.0 mg / L of extract;and / or - a quercetin concentration of between 1.0 and 5.0 mg / L of extract.

3. Extract according to any of claims 1 or 2, characterized in that it comprises: - a procyanidin concentration of B1+B2+C1 of between 60 and 130 mg / L of extract.

4. Extract according to any of claims 1 to 3, characterized in that it comprises: - a catechin concentration of between 50 and 70 mg / L of extract.

5. Extract according to any of claims 1 to 4, characterized in that it comprises: - an epicatechin concentration of between 50 and 70 mg / L of extract.

6. Extract according to any of claims 1 to 5, characterized in that it comprises: - an epicatechin gallate concentration of between 5 and 20 mg / L of extract.

7. Extract according to any of claims 1 to 6, characterized in that it comprises: - a concentration of procyanidins B1+B2+C1 of between 60 and 130 mg / L of extract; - a concentration of catechin of between 50 and 70 mg / L of extract;- an epicatechin concentration of between 50 and 70 mg / L of extract; and - an epicatechin gallate concentration of between 5 and 20 mg / L of extract.; 8. Extract according to any of claims 1 to 7, characterized in that it comprises: - a gallic acid concentration of between 10 and 40 mg / L of extract; - a 2,4,6-trihydrobenzoic acid concentration of between 1 and 3 mg / L of extract; - a caftaric acid concentration of between 4 and 7 mg / L of extract; - a procyanidin B1+B2+C1 concentration of between 60 and 130 mg / L of extract; - a catechin concentration of between 50 and 70 mg / L of extract; - an epigallocatechin gallate concentration of between 1 and 3 mg / L of extract; - an epicatechin concentration of between 50 and 70 mg / L of extract; - an epicatechin gallate concentration of between 5 and 20 mg / L of extract; - a quercetin-3-glucuronide concentration of between 10 and 25 mg / L of extract extract;- a concentration of quercetin-3-rutinoside of between 0.2 and 1 mg / L of extract;- a concentration of quercetin-3-glucoside of between 10 and 25 mg / L of extract;- a kaempferol concentration of between 0.1 and 3 mg / L of extract; and - a quercetin concentration of between 1 and 5 mg / L of extract.

9. Extract according to any one of claims 1 to 8, characterized in that it comprises at least one of the following: - a malic acid concentration of between 100 and 210 mg / L of extract; and / or - a maleic acid concentration of between 150 and 240 mg / L of extract.

10. Process for obtaining a white grape extract as defined in any one of claims 1 to 9, characterized in that it comprises the steps of: a) Providing a mixture comprising white grape pomace and optionally a dispersant; b) Eluting the mixture with a solvent comprising propylene glycol and / or acetone; c) Collecting the white grape extract obtained after elution;(d) Optionally, eliminate the solvent.

11. A process according to claim 10, characterized in that a dispersant is used in step (a).

12. A process according to any one of claims 10 to 11, characterized in that a dispersant selected from the group consisting of sand, Florisil, C18, alumina, and silica gel is used in step (a).

13. A process according to claim 10 to 12, characterized in that the solvent comprises propylene glycol or acetone.

14. A process according to any one of claims 10 to 13, characterized in that the solvent also comprises water.

15. A process according to any one of claims 10 to 14, characterized in that, after collecting the white grape extract, step (c) further comprises recirculating the eluate obtained from the mixture of step (a).

16. A process according to any one of claims 10 to 15, characterized in that it comprises an additional step (d), carried out after step (c), of solvent reduction.

17. A process according to any one of claims 10 to 16, characterized in that step (d) comprises an evaporation, freeze-drying, and / or spray-drying step.

18. A process according to any one of claims 10 to 17, characterized in that step (d) comprises removing solvent to a final amount of not more than 20%, preferably not more than 1% solvent. 19.A process according to any one of claims 10 to 18, characterized in that step (d) comprises a solvent evaporation step, followed by a lyophilization and / or spray drying step, thereby producing the solid extract.

20. White grape extract characterized in that it is an extract obtainable according to any one of claims 10 to 19.

21. Pharmaceutical composition characterized in that it is a composition for intramammary administration comprising, as an active ingredient, the white grape extract defined in any one of claims 1 to 9, or the extract defined in claim 20.

22. Pharmaceutical composition according to claim 21, characterized in that it is an injectable composition.

23. Pharmaceutical composition according to any one of claims 21 to 22, characterized in that it is an emulsion or dispersion. 24.Pharmaceutical composition according to any of claims 21 to 23, characterized in that it is an emulsion comprising an aqueous phase, an oily phase and a surfactant, wherein: -the aqueous phase comprises purified water for injection, ethanol, isopropanol, propanol, propylene glycol, or mixtures thereof; and / or -the oily phase comprises paraffin oil.

25. Pharmaceutical composition according to any one of claims 21 to 24, characterized in that it comprises a biodegradable carboxypolymethylene polymer Carbopol®.

26. Pharmaceutical composition according to claim 25, characterized in that it comprises from 0.5 to 4% of said biodegradable polymer, preferably from 1 to 4%.

27. Pharmaceutical composition according to any one of claims 21 to 26, characterized in that it is for administration in a non-human mammal, preferably cows, camels, buffalo, goats, or sheep.

28. Intramammary syringe comprising the pharmaceutical composition according to any one of claims 21 to 27.

29. Intramammary syringe according to claim 28, characterized in that it comprises a biodegradable carboxypolymethylene polymer Carbopol®.

30. Intramammary syringe according to claim 29, characterized in that it comprises from 0.5 to 4% of said biodegradable polymer, preferably from 1 to 4%. 31.

31. Pharmaceutical composition for use in the treatment and / or prevention of mastitis in a non-human mammal, characterized in that it is a composition for intramammary administration comprising, as an active ingredient, the white grape extract defined in any one of claims 1 to 9, or the extract defined in claim 20.

32. Pharmaceutical composition for use according to claim 31, characterized in that it comprises a biodegradable carboxypolymethylene polymer Carbopol®.

33. Pharmaceutical composition for use according to claim 32, characterized in that it comprises from 0.5 to 4% of said biodegradable polymer, preferably from 1 to 4%.

34. Extract according to any one of claims 1 to 9, or according to claim 20, for use in the treatment and / or prevention of mastitis in a non-human mammal.

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