MD1629Z - Anti-SARS-CoV-2 phytotherapeutic food additive - Google Patents
Anti-SARS-CoV-2 phytotherapeutic food additive Download PDFInfo
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- MD1629Z MD1629Z MDS20210062A MDS20210062A MD1629Z MD 1629 Z MD1629 Z MD 1629Z MD S20210062 A MDS20210062 A MD S20210062A MD S20210062 A MDS20210062 A MD S20210062A MD 1629 Z MD1629 Z MD 1629Z
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- 239000002778 food additive Substances 0.000 title 1
- 235000013373 food additive Nutrition 0.000 title 1
- 235000015872 dietary supplement Nutrition 0.000 claims abstract description 18
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- Medicines Containing Plant Substances (AREA)
Abstract
Invenţia se referă la industria alimentară, sanocreatologie şi medicină, în special la un supliment alimentar fitoterapeutic, biologic activ, care posedă activitate imunostimulatoare cu inhibarea virusului SARS-CoV-2. Suplimentul alimentar, conform invenţiei, conţine extracte uscate din, în %mas.:partea aeriană de pelin, Artemisia vulgaris16±3partea aeriană de cornet, Xanthium strumarium16±3rădăcină de maral, Rhaponticum carthamoides6±2coajă de nucă, Juglans regia11±2rădăcină de hrean, Armoracia rusticana10±3partea aeriană de leuştean, Levisticum officinale13±3colţii babei, Tribulus terrestris L.16±3rădăcină de ghimbir, Zingiberofficinale6±2rădăcină de lemn dulce, Glycyrrhiza glabra6±2.The invention relates to the food industry, sanocratology and medicine, in particular to a phytotherapeutic, biologically active food supplement, which possesses immunostimulating activity with the inhibition of the SARS-CoV-2 virus. The food supplement, according to the invention, contains dry extracts from, in %wt.: aerial part of wormwood, Artemisia vulgaris16±3 aerial part of cornet, Xanthium strumarium16±3 maral root, Rhaponticum carthamoides6±2 walnut shell, Juglans regia11±2 horseradish root, Armoracia rusticana10±3 aerial part of larkspur, Levisticum officinale13±3 cloves, Tribulus terrestris L.16±3 ginger root, Zingiberofficinale6±2 licorice root, Glycyrrhiza glabra6±2.
Description
Invenţia se referă la industria alimentară, sanocreatologie şi medicină, în special la un supliment alimentar fitoterapeutic, biologic activ, care posedă activitate imunostimulatoare cu inhibarea virusului SARS-CoV-2. The invention relates to the food industry, sanocreatology and medicine, in particular to a phytotherapeutic, biologically active food supplement, which possesses immunostimulating activity with inhibition of the SARS-CoV-2 virus.
Este cunoscută utilizarea compoziţiei farmaceutice care conţine: alcool 2,4-dichlorbenzyl în combinaţie cu amilmetacrezolom destinată profilaxiei şi tratamentului infecţiilor virale provocate de coronavirusul SARS cu fenotipul Urbani. Această compoziţie se poate afla atât în stare lichidă, cât şi în stare solidă [1]. It is known to use a pharmaceutical composition containing: 2,4-dichlorobenzyl alcohol in combination with amylmetacresol for the prophylaxis and treatment of viral infections caused by SARS coronavirus with the Urbani phenotype. This composition can be in both liquid and solid state [1].
Dezavantajul acestei compoziţii, constă în faptul că ingredientele ei reprezintă antiseptice şi au acţiune numai la nivel local, totodată această compoziţie nu are efect în cazul coronavirusului SARS-CoV-2. The disadvantage of this composition is that its ingredients are antiseptics and have action only locally, and this composition has no effect on the SARS-CoV-2 coronavirus.
Mai este cunoscută compoziţia care conţine extract apos din frunze şi tulpini de coacăză neagră, care face parte din genul Ribes şi anume Ribes nigrum L., destinat tratamentului infecţiilor virale provocate de rinoviruşi, adenoviruşi, coronaviruşi, retroviruşi şi gripă, totodată a fost observat şi efectul de a inhiba infecţia virală provocată de HIV1 şi HIV2 [2]. The composition containing aqueous extract from blackcurrant leaves and stems, which is part of the Ribes genus, namely Ribes nigrum L., is also known, intended for the treatment of viral infections caused by rhinoviruses, adenoviruses, coronaviruses, retroviruses and influenza, and the effect of inhibiting viral infection caused by HIV1 and HIV2 has also been observed [2].
Dezavantajul acestei compoziţii constă în faptul că nu are efect în cazul coronavirusului SARS-CoV-2. The disadvantage of this composition is that it has no effect on the SARS-CoV-2 coronavirus.
Mai este cunoscută compoziţia destinată tratamentului SARS-CoV-2, care include, în %: 43-44 favipiravir micronizat cu o dimensiune a particulelor de 40-50 µm, 5,5-6,0 croscarmeloză sodică, 4,8-5,0 povidonă, 0,6-0,8 stearat de magneziu, 0,5-0,7 dioxid de siliciu coloidal, 2,5-2,7 înveliş de film, iar restul este celuloză microcristalină, durata de tratament cu acest remediu, constituie în medie 10 zile [3]. The composition intended for the treatment of SARS-CoV-2 is also known, which includes, in %: 43-44 micronized favipiravir with a particle size of 40-50 µm, 5.5-6.0 croscarmellose sodium, 4.8-5.0 povidone, 0.6-0.8 magnesium stearate, 0.5-0.7 colloidal silicon dioxide, 2.5-2.7 film coating, and the rest is microcrystalline cellulose, the duration of treatment with this remedy is on average 10 days [3].
Dezavantajul acestei compoziţii constă în faptul că reprezintă un remediu medicamentos care se prescrie numai prin reţetă, iar pentru a obţine reţeta trebuie de vizitat medicul într-o instituţie medicală, totodată persoanele care suferă de SARS-CoV-2 sunt o sursă de infecţie, care pot răspândi infecţia în instituţiile medicale şi în rândurile medicilor, în acelaşi timp costul unei cutii de acest remediu este de 145 Euro, ceea ce face dificilă accesibilitatea la tratament a persoanelor social vulnerabile, totodată medicamentul nu are efect antioxidant, iar în cazul infectării cu SARS-CoV-2 creşte intoxicaţia, iar efectul antioxidant este vital necesar. Administrarea acestui remediu poate duce la reacţii adverse ca: leucopenie, creşterea ALAT şi ASAT, a nivelului de trigliceride şi de acid uric, prin urmare, administrarea acestui remediu poate fi contraindicată persoanelor ce suferă de podagră, insuficienţă cardiacă şi hepatică. The disadvantage of this composition is that it is a medicinal remedy that is prescribed only by prescription, and to obtain the prescription you must visit a doctor in a medical institution, at the same time, people suffering from SARS-CoV-2 are a source of infection, who can spread the infection in medical institutions and among doctors, at the same time the cost of a box of this remedy is 145 Euros, which makes it difficult for socially vulnerable people to access treatment, at the same time the medicine does not have an antioxidant effect, and in the case of infection with SARS-CoV-2, intoxication increases, and the antioxidant effect is vitally necessary. The administration of this remedy can lead to adverse reactions such as: leukopenia, increased ALAT and ASAT, triglyceride and uric acid levels, therefore, the administration of this remedy may be contraindicated for people suffering from gout, heart and liver failure.
Mai este cunoscut suplimentul alimentar, care conţine extract alcoolic din: partea aeriană de pelin, partea aeriană de cornet, rădăcină de maral, coajă de nucă, rădăcină de hrean şi partea aeriană de leuştean, obţinut la extragerea cu alcool etilic de 96,4% vol., în raport respectiv de 1:(4-5), timp de 15-21 de zile, precum şi apă purificată, restul, până la atingerea unei tării de 32-35% vol. [4]. The food supplement is also known, which contains alcoholic extract from: the aerial part of wormwood, the aerial part of cornel, maral root, walnut shell, horseradish root and the aerial part of lovage, obtained by extraction with 96.4% vol. ethyl alcohol, in the respective ratio of 1:(4-5), for 15-21 days, as well as purified water, the rest, until reaching a strength of 32-35% vol. [4].
Dezavantajul acestei soluţii constă în faptul că suplimentul descris mai sus nu acţionează asupra întregului lanţ patogenetic, datorită cărui fapt se menţin procese de agregare sanguină, şi de creştere a tensiunii arteriale, totodată nu acţionează asupra nivelului de glicemie, dar se cunoaşte că persoanele cu comorbidităţi fac o formă mai agresivă de boală. Deci, este important nu numai factorul imunostimulator, dar şi neadmiterea agregării sanguine şi creşterii glicemiei. The disadvantage of this solution is that the supplement described above does not act on the entire pathogenetic chain, due to which the processes of blood aggregation and blood pressure increase are maintained, and it also does not act on the blood sugar level, but it is known that people with comorbidities develop a more aggressive form of the disease. Therefore, it is important not only the immunostimulating factor, but also the prevention of blood aggregation and blood sugar increase.
Problema tehnică a invenţiei constă în lărgirea gamei de suplimente alimentare, care posedă efect imunostimulator, cu inhibarea virusului SARS-CoV-2, bazat numai pe ingrediente fitoterapeutice, care poate fi eliberat persoanelor fără reţetă, nu ar provoca reacţii adverse şi ar diminua agregarea sangvină, tensiunea arterială şi glicemia. Dat fiind faptul că o parte din bolnavii infectaţi cu SARS-CoV-2 suferă de un şir de patologii asociate (diabet, hipertensiune arterială, ateroscleroză), aceşti factori devin primordiali în tratamentul acestei maladii. The technical problem of the invention consists in expanding the range of food supplements, which have an immunostimulating effect, with inhibition of the SARS-CoV-2 virus, based only on phytotherapeutic ingredients, which can be released to people without a prescription, would not cause adverse reactions and would reduce blood aggregation, blood pressure and blood sugar. Given the fact that some of the patients infected with SARS-CoV-2 suffer from a number of associated pathologies (diabetes, hypertension, atherosclerosis), these factors become paramount in the treatment of this disease.
Invenţia soluţionează problema prin aceea că se propune un supliment alimentar fitoterapeutic care conţine extracte uscate din, în %mas.: The invention solves the problem by proposing a phytotherapeutic food supplement containing dry extracts of, in %wt.:
partea aeriană de pelin, Artemisia vulgaris 16±3 aerial part of wormwood, Artemisia vulgaris 16±3
partea aeriană de cornet, Xanthium strumarium 16±3 aerial part of cornel, Xanthium strumarium 16±3
rădăcină de maral, Rhaponticum carthamoides 6±2 maral root, Rhaponticum carthamoides 6±2
coajă de nucă, Juglans regia 11±2 walnut shell, Juglans regia 11±2
rădăcină de hrean, Armoracia rusticana 10±3 horseradish root, Armoracia rusticana 10±3
partea aeriană de leuştean, Levisticum officinale 13±3 aerial part of lovage, Levisticum officinale 13±3
colţii babei, Tribulus terrestris L. 16±3 Tribulus terrestris L. 16±3
rădăcină de ghimbir, Zingiber officinale 6±2 ginger root, Zingiber officinale 6±2
rădăcină de lemn dulce, Glycyrrhiza glabra 6±2. licorice root, Glycyrrhiza glabra 6±2.
Rezultatul invenţiei revendicate constă în lărgirea gamei de suplimente alimentare fitoterapeutice, biologic active, care posedă activitate imunostimulatoare cu inhibarea virusul SARS-CoV-2 şi care acţionează asupra întregului lanţ patologic datorită selectării reuşite a raportului cantitativ şi calitativ al componentelor care manifestă sinergism şi produc un efect imunostimulator, antiagregant pronunţat, diminuează tensiunea arterială şi glicemia. The result of the claimed invention consists in expanding the range of phytotherapeutic, biologically active food supplements, which possess immunostimulating activity with inhibition of the SARS-CoV-2 virus and which act on the entire pathological chain due to the successful selection of the quantitative and qualitative ratio of the components that manifest synergism and produce a pronounced immunostimulating, antiplatelet effect, reduce blood pressure and blood sugar.
Suplimentul alimentar fitoterapeutic, biologic activ are următoarele avantaje: The phytotherapeutic, biologically active food supplement has the following advantages:
- este simplu în tehnologia de preparare; - it is simple in preparation technology;
- nu necesită a fi prescris prin reţetă, deoarece nu reprezintă un medicament; - does not require a prescription, as it is not a medicine;
- are un efect imunostimulator cu inhibarea virusului SARS-CoV-2; - has an immunostimulatory effect by inhibiting the SARS-CoV-2 virus;
- sporeşte cantitatea de IgG, IgM şi IgA; - increases the amount of IgG, IgM and IgA;
- are efect antiagregant; - has an antiplatelet effect;
- diminuează tensiunea arterială; - lowers blood pressure;
- diminuează glicemia. - reduces blood sugar.
Proprietăţile imunostimulatoare ale suplimentului alimentar revendicat au fost testate la pacienţii cu SARS-CoV-2 cu evoluţie medie a bolii (tabelele 1 şi 2). The immunostimulating properties of the claimed dietary supplement were tested in patients with SARS-CoV-2 with moderate disease progression (tables 1 and 2).
Tabelul 1 Table 1
Influenţa terapiei cu supliment alimentar asupra dinamicii indicilor imunoglobulinelor la pacienţii cu infecţie SARS-CoV-2 în formă medie Influence of dietary supplement therapy on the dynamics of immunoglobulin indices in patients with moderate SARS-CoV-2 infection
Imunoglobulinele În ziua spitalizării Lotul experimental Lotul de control Ziua a 5-a Ziua a 14-a Ziua a 5-a Ziua a 14-a IgM 32±0,1 44±0,1 46±0,1 32±0,1 36±0,1 IgG 581±0,1 685±0,1 697±0,1 582±0,1 665±0,1 IgA 63±0,1 72±0,1 75±0,1 64±0,1 66±0,1Immunoglobulins On the day of hospitalization Experimental group Control group Day 5 Day 14 Day 5 Day 14 IgM 32±0.1 44±0.1 46±0.1 32±0.1 36±0.1 IgG 581±0.1 685±0.1 697±0.1 582±0.1 665±0.1 IgA 63±0.1 72±0.1 75±0.1 64±0.1 66±0.1
Pacienţii din lotul de control (40 persoane) au primit tratament conform protocolului adoptat la „Centrul COVID-19”. Lotul experimental (40 persoane) a primit suplimentul alimentar revendicat adjuvant la protocolul de bază, în cantitate de 6 capsule pe zi. Patients in the control group (40 people) received treatment according to the protocol adopted at the "COVID-19 Center". The experimental group (40 people) received the claimed dietary supplement as an adjunct to the basic protocol, in the amount of 6 capsules per day.
Rezultatele cercetării sunt prezentate în tabelul 1. The research results are presented in Table 1.
Datele obţinute indică faptul că suplimentul alimentar propus are un efect imunostimulator. Nivelul IgM la pacienţii care au primit suplimentul alimentar în a 5-a zi a fost de 44±0,1, comparativ cu 32±0,1 în lotul de control. În ziua a 14-a, nivelul IgM în lotul experimental a fost de 46±0,1, faţă de 36±0,1 în lotul de control, de aici deducem o creştere esenţială a IgM. O tendinţă similară a fost observată în concentraţia de IgG şi IgA. The obtained data indicate that the proposed dietary supplement has an immunostimulating effect. The IgM level in patients who received the dietary supplement on the 5th day was 44±0.1, compared to 32±0.1 in the control group. On the 14th day, the IgM level in the experimental group was 46±0.1, compared to 36±0.1 in the control group, from which we deduce an essential increase in IgM. A similar trend was observed in the concentration of IgG and IgA.
Dinamica semnelor clinice la pacienţii cu diagnostic de SARS-CoV-2, formă medie, trataţi cu suplimentul biologic activ revendicat pe un lot de 80 de pacienţi, dintre care 40 - grupul de studiu şi 40 - grupul de control, este reprezentată în tabelul 2. The dynamics of clinical signs in patients diagnosed with SARS-CoV-2, moderate form, treated with the claimed biologically active supplement in a group of 80 patients, of which 40 - the study group and 40 - the control group, is represented in Table 2.
Tabelul 2 Table 2
Semnele clinice Grupul de studiu Grupul de control La momentul adresării, nr. pacienţi În a 5-a zi a tratamentului În a 14-a zi a tratamentului La momentul adresării, nr. pacienţi În a 5-a zi a tratamentului În a 14-a zi a tratamentului 1.Starea generală 2. Temperatura 3. Rinoree, lipsa mirosului şi gustului 4. Dureri în gât 5. Tuse uscată 6. Disfuncţii respiratorii 7. Dureri în piept 40 satisf. 40(39±0,02) 18 5 6 6 FR≤26±1 5 40 satisf. 40(37±0,02) - - - 40 FR≤20±1 - - - - - - - - 40 satisf. 40(39±0,02) 18 6 5 9 FR≤26±1 2 40 satisf. 40(38±0,02) 16 6 5 9 FR≤26±1 4 40 satisf. 40(36,6±0,01) - - - 40 FR≤23±1 -Clinical signs Study group Control group At the time of referral, no. patients On the 5th day of treatment On the 14th day of treatment At the time of referral, no. patients On the 5th day of treatment On the 14th day of treatment 1.General condition 2. Temperature 3. Rhinorrhea, loss of smell and taste 4. Sore throat 5. Dry cough 6. Respiratory dysfunction 7. Chest pain 40 satis. 40(39±0.02) 18 5 6 6 FR≤26±1 5 40 satis. 40(37±0.02) - - - 40 FR≤20±1 - - - - - - - - 40 satis. 40(39±0.02) 18 6 5 9 FR≤26±1 2 40 satis. 40(38±0.02) 16 6 5 9 FR≤26±1 4 40 satis. 40(36.6±0.01) - - - 40 FR≤23±1 -
Dinamica tensiunii arteriale şi a glicemiei la pacienţii cu diagnostic de SARS-CoV-2, formă medie, trataţi cu suplimentul biologic activ revendicat pe un lot de 80 de pacienţi, a fost următoarea: la pacienţii care au urmat suplimentul alimentar revendicat tensiunea arterială s-a diminuat în mediu cu 20 unităţi ai coloanei de mercur, comparativ cu grupul de control, iar glicemia s-a diminuat cu 2-3 mmol/L, faţă de indicii din grupul de control, totodată s-a atestat şi un efect antiagregant pronunţat, cantitatea fibrinogenului a fost cu 40% mai mică în raport cu grupul de control. The dynamics of blood pressure and blood sugar in patients diagnosed with SARS-CoV-2, moderate form, treated with the claimed biologically active supplement in a group of 80 patients, was as follows: in patients who took the claimed dietary supplement, blood pressure decreased on average by 20 units of mercury column, compared to the control group, and blood sugar decreased by 2-3 mmol/L, compared to the indices in the control group, at the same time a pronounced antiplatelet effect was also attested, the amount of fibrinogen was 40% lower compared to the control group.
Rezultatele obţinute demonstrează convingător activitatea antivirală sporită a suplimentului împotriva virusului SARS-CoV-2, precum şi efectul antihipertensiv, antiagregant şi hipoglicemic al acestiua. The results obtained convincingly demonstrate the supplement's enhanced antiviral activity against the SARS-CoV-2 virus, as well as its antihypertensive, antiplatelet and hypoglycemic effect.
Exemplu de realizare a invenţiei. Example of embodiment of the invention.
Pacienta A., vârsta de 55 ani, internată la Centrul COVID-19, la internare: starea generală - satisfăcătoare, temperatura - 39°C, rinoree, lipsa mirosului şi gustului, dureri în gât, tuse uscată, disfuncţie respiratorie - FR 27, dureri în piept, testul la SARS-CoV-2 - pozitiv (prin testare din nazo- şi orofaringe), T/A 170/110 mmHg, glicemia 8 mmol/L, cantitatea de fibrinogen 130%. După administrarea suplimentului fitoterapeutic biologic activ timp de 5 zile toate semnele clinice au dispărut, testul la SARS-CoV-2 - negativ (prin testare din nazo- şi orofaringe), T/A - 150/90 mmHg, glicemia 6 mmol/L, iar cantitatea de fibrinogen a constituit - 90%. Patient A., 55 years old, admitted to the COVID-19 Center, upon admission: general condition - satisfactory, temperature - 39°C, rhinorrhea, loss of smell and taste, sore throat, dry cough, respiratory dysfunction - FR 27, chest pain, SARS-CoV-2 test - positive (by testing from the naso- and oropharynx), T/A 170/110 mmHg, blood glucose 8 mmol/L, fibrinogen amount 130%. After administration of the biologically active phytotherapeutic supplement for 5 days, all clinical signs disappeared, SARS-CoV-2 test - negative (by testing from the naso- and oropharynx), T/A - 150/90 mmHg, blood glucose 6 mmol/L, and the amount of fibrinogen was - 90%.
Modul de preparare a suplimentului alimentar propus este următorul: componentele suplimentului sunt procurate de la întreprinderea Compania EPO (Estratti Piante Officinali) L.t.d, Italia şi reprezintă extracte vegetale uscate, standardizate 1:10, din materie vegetala pentru industria farmaceutică: partea aeriană de pelin, partea aeriană de cornet, rădăcină de maral, coajă de nucă, rădăcină de hrean, partea aeriană de leuştean, colţii babei, rădăcină de ghimbir şi rădăcină de lemn dulce, extractele se amestecă în următorul raport al componentelor, în %mas.: 16, 16, 6, 11, 10, 13, 16, 6 şi 6, se amestecă bine timp de 3 min, până se obţine o masă omogenă. Masa obţinută este de culoare brun-verzuie, ulterior aceasta se încapsulează în capsule gelatinoase tari de diferite mărimi începând cu mărimile 0; 1. Suplimentul în capsule se ambalează în flacoane din plastic a câte 90 capsule, însoţite de prospectul de utilizare. The method of preparation of the proposed food supplement is as follows: the components of the supplement are purchased from the company EPO (Estratti Piante Officinali) L.t.d, Italy and represent dried plant extracts, standardized 1:10, from plant material for the pharmaceutical industry: aerial part of wormwood, aerial part of cornel, maral root, walnut shell, horseradish root, aerial part of lovage, elderberry fangs, ginger root and licorice root, the extracts are mixed in the following ratio of components, in % mass: 16, 16, 6, 11, 10, 13, 16, 6 and 6, mix well for 3 min, until a homogeneous mass is obtained. The mass obtained is brown-greenish in color, then it is encapsulated in hard gelatin capsules of various sizes starting with sizes 0; 1. The capsule supplement is packaged in plastic bottles of 90 capsules, accompanied by the instructions for use.
Exemplu concret de preparare a suplimentului fitoterapeutic: se selectează ingredientele, se amestecă după cum urmează, în %mas., extractele uscate din: partea aeriană de pelin 16, partea aeriană de cornet 16, rădăcină de maral 6, coajă de nucă 11, rădăcină de hrean 10, partea aeriană de leuştean 13, colţii babei 16, rădăcină de ghimbir 6 şi rădăcină lemn de dulce 6, se amestecă bine timp de 3 min, până se obţine o masă omogenă. Masa obţinută de culoare brun-verzuie se încapsulează în capsule gelatinoase tari de diferite mărimi începând cu mărimile 0; 1. Suplimentul în capsule se ambalează în flacoane din plastic a câte 90 capsule, însoţite de prospectul de utilizare. Concrete example of preparation of the phytotherapeutic supplement: select the ingredients, mix as follows, in %wt., the dry extracts of: wormwood aerial part 16, cornel aerial part 16, maral root 6, walnut shell 11, horseradish root 10, lovage aerial part 13, elderberry fangs 16, ginger root 6 and licorice root 6, mix well for 3 min, until a homogeneous mass is obtained. The obtained greenish-brown mass is encapsulated in hard gelatin capsules of various sizes starting with sizes 0; 1. The supplement in capsules is packaged in plastic bottles of 90 capsules each, accompanied by the user leaflet.
Suplimentul alimentar se administrează câte 2 capsule de 3 ori pe zi cu 15 min înainte de masă. The dietary supplement is administered 2 capsules 3 times a day 15 minutes before meals.
Acesta poate fi recomandat pentru includerea în componenţa produselor alimentare fitoterapeutice predestinate sporirii potenţialului imunostimulator şi antiviral al organismului cu efect antiagregant şi hipoglicemic şi prescris în tratarea infecţiei SARS-CoV-2. It can be recommended for inclusion in phytotherapeutic food products intended to increase the body's immunostimulatory and antiviral potential with antiplatelet and hypoglycemic effects and prescribed in the treatment of SARS-CoV-2 infection.
Tehnologia de preparare a suplimentului alimentar este accesibilă şi necostisitoare. The technology for preparing the dietary supplement is accessible and inexpensive.
1. RU 2366411 C2 2009.09.10 1. RU 2366411 C2 2009.09.10
2. RU 2505306 C2 2014.09.10 2. RU 2505306 C2 2014.09.10
3. RU 2731932 C1 2020.09.09 3. RU 2731932 C1 2020.09.09
4. MD 1532 Y 2021.05.31 4. MD 1532 Y 2021.05.31
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