WO2024005747A1 - Antiviral nasal spray - Google Patents
Antiviral nasal spray Download PDFInfo
- Publication number
- WO2024005747A1 WO2024005747A1 PCT/TR2023/050419 TR2023050419W WO2024005747A1 WO 2024005747 A1 WO2024005747 A1 WO 2024005747A1 TR 2023050419 W TR2023050419 W TR 2023050419W WO 2024005747 A1 WO2024005747 A1 WO 2024005747A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tannic acid
- virus
- nasal spray
- coronavirus
- dill oil
- Prior art date
Links
- 230000000840 anti-viral effect Effects 0.000 title claims abstract description 23
- 239000007922 nasal spray Substances 0.000 title claims abstract description 20
- 229940097496 nasal spray Drugs 0.000 title claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 18
- 238000009472 formulation Methods 0.000 claims abstract description 15
- 239000010621 dill oil Substances 0.000 claims description 36
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 claims description 35
- 239000001263 FEMA 3042 Substances 0.000 claims description 35
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims description 35
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 claims description 35
- 229940033123 tannic acid Drugs 0.000 claims description 35
- 235000015523 tannic acid Nutrition 0.000 claims description 35
- 229920002258 tannic acid Polymers 0.000 claims description 35
- 239000008055 phosphate buffer solution Substances 0.000 claims description 9
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 5
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 4
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 239000002504 physiological saline solution Substances 0.000 claims description 2
- 241000700605 Viruses Species 0.000 abstract description 32
- 239000004615 ingredient Substances 0.000 abstract description 5
- 230000009931 harmful effect Effects 0.000 abstract description 2
- 241000711573 Coronaviridae Species 0.000 description 25
- 230000000694 effects Effects 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 230000002779 inactivation Effects 0.000 description 7
- 210000002850 nasal mucosa Anatomy 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000013543 active substance Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
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- 208000025721 COVID-19 Diseases 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000000415 inactivating effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- 230000009469 supplementation Effects 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 2
- 239000000850 decongestant Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000011146 sterile filtration Methods 0.000 description 2
- 230000003319 supportive effect Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 241000711443 Bovine coronavirus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000002979 Influenza in Birds Diseases 0.000 description 1
- 208000025370 Middle East respiratory syndrome Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010062106 Respiratory tract infection viral Diseases 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000000222 aromatherapy Methods 0.000 description 1
- 206010064097 avian influenza Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
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- 230000007812 deficiency Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000531 effect on virus Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
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- 230000001502 supplementing effect Effects 0.000 description 1
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- 201000010740 swine influenza Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
Definitions
- the invention relates to an antiviral nasal spray for use in the healthcare sector and other pharmaceutical products that will be developed with the same active ingredients therefrom.
- the invention particularly relates to a novel antiviral nasal spray that provides a high level of suppression against the virus by means of the active ingredient content of dill oil and tannic acid.
- the respiratory system comes to the fore as a transmission route.
- Viruses that are the causative agents of the disease after entering the body through the respiratory air, mainly cling to the nasal mucosa and initiate infection.
- the virus that multiplies here then either goes to the lungs and causes pneumonia, or spreads through the blood to the body, leading to a systemic (general) disease situation.
- the treatment options and chances of success for viral infections decrease significantly. Therefore, the most appropriate way to prevent or reduce the damage caused by such infections is to stop the virus at the point of entry into the body, which is still the initial stage of infection, that is, in the nasal mucosa.
- US2019166903 A1 describes an apparatus for vaporizable liquid composition developed for personal use. However, there is no explanation for the combined use of dill oil and tannic acid in the said application.
- WO2021206688 A1 relates to a compound developed for aromatherapy. However, there is no explanation for the combined use of dill oil and tannic acid in the said application.
- the present invention relates to an antiviral nasal spray that meets the requirements mentioned above, eliminates all the disadvantages, and provides some additional advantages.
- the invention is inspired by the present situations and aims to solve the disadvantages mentioned above.
- the main object of the invention is to develop a new formulation of antiviral nasal spray.
- the formulation which is the subject of the invention, comprises natural ingredients that inactivate the virus and prevent it from multiplying without having a harmful effect on the cells.
- the main technical advantages of the antiviral nasal spray formulation are given below.
- Phosphate buffer solution (pH 6.00): It is carriage substance of the formulation and increases the antimicrobial activity in the nasal mucosa by means of its adjusted pH.
- the invention relates to an antiviral nasal spray for use in the healthcare sector.
- the formulation of the antiviral nasal spray contains dill oil and tannic acid as active ingredients, polyvinyl alcohol, benzalkonium chloride, phosphate buffer solution as auxiliary substances.
- the pH of the phosphate buffer solution is preferably 6.
- dill oil and tannic acid are mandatory ingredients of antiviral nasal spray.
- Glycerin can be used instead of polyvinyl alcohol.
- physiological saline can be used instead of phosphate buffer solution.
- the ingredients contained in the antiviral nasal spray formulation content, the intervals of use and the preferred amounts of use are given in the following table.
- Dill oil is an herbal extract product comprising fatty acids with antiviral, antimicrobial and antioxidant activity.
- coronavirus In experimental applications with coronavirus, it has been determined that it inactivates viruses in the medium at a rate of more than 98% for 4 hours, suppresses the entry of the virus into cells at a rate of more than 90%, and its reproduction in the cell at a rate of 99.58%.
- Tannic acid is a compound with antiviral and antimicrobial activity and is found naturally in various plants. In experimental applications with coronavirus, it has been determined that it inactivates viruses in the medium at a rate of more than 98.2% for 4 hours, suppresses the entry of the virus into cells at a rate of more than 58%, and its reproduction in the cell at a rate of up to 100%.
- Polyvinyl alcohol by means of its structural property, allows the active substance components to remain in the nasal mucosa for a longer time and effectively.
- Benzalkonium chloride provides a supportive effect in reducing mucosa damage due to virus infection by means of its anti-inflammatory and decongestant effect.
- Phosphate buffer solution (pH 6.00) essentially acts as a vehicle substance in the formulation, but it supports the physiological defense barrier of the nasal mucosa by means of its balanced pH value.
- the pH level has been selected as the level with the highest antimicrobial activity in the nasal mucosa. Antiviral effectiveness may decrease if this value is changed upwards.
- the antiviral nasal spray which is the subject of the invention, has been prepared for use in order to prevent the onset or progression of respiratory viral infections.
- Non-sick individuals can use it to protect themselves against the virus, while sick individuals can use it to slow the progression of the disease and reduce contagion.
- spray is applied to both nasal cavities 1-2 times. This application should be performed 4 times a day at intervals of six hours. Due to its natural content, it can also be applied at shorter intervals when needed.
- PBS phosphate buffer solution
- PBS is prepared without calcium, and it is sterilized.
- it is started to be spinned in a magnetic mixer in a glass container.
- Dill oil preferably at a rate of 0.006-0.015% (v/v)
- Tannic acid preferably at a rate of 30-70 pM
- the added T is in powder form.
- the next added ingredient is polyvinyl alcohol (preferably 7-14 mg/ml).
- benzalkonium chloride preferably 0.01-0.04mg/ml is added.
- the resulting final product is mixed for 30 - 60 minutes at a speed of 200 rpm, preferably at room temperature. Then, it is passed through preferably 0.2 pm membrane filter and sterile filtration process is applied.
- the final processing step is the filling process. In this process, glass or plastic spray light-proof bottles are filled. In this method, mixing is performed at a temperature of 21-24 ID for 30-60 minutes, sterile filtration is performed at a temperature of 21-24 ID, storage is performed at a temperature of 21-24 ‘C.
- Dill oil An herbal essential oil
- Tannic acid A powdered compound derived from plants
- BCoV Coronavirus used in the study (Bovine coronavirus)
- Virus titers obtained in the treatment of dill oil live virus numbers
- Virus inhibition rates obtained by dill oil treatment % (virus inactivation rate)
- Figure 3 shows the effectiveness of dill oil and tannic acid (together) on coronavirus versus time.
- Figure 4 shows the effect of dill oil and tannic acid on coronavirus reproduction together and with active ingredient supplementation at 48-hour intervals.
- Figure 5 shows the adsorption and penetration rates.
- the potential of dill oil and tannic acid to prevent the penetration of coronavirus into the cell in the medium was tested when they are used separately and together. According to the data obtained, while the adsorption was stopped by 68.38% when the T substance was used alone, it achieved 90% success when the D substance was used alone. However, when the two components are used together, this ratio increases to 98.58%. This is one of the most prominent unexpected findings of this study.
- Figure 6 shows the effect of dill oil and tannic acid (together) on inactivating the coronavirus present in the medium.
- the potential of inactivating the coronavirus present in the medium was tested when dill oil and tannic acid are used separately and together.
- the inactivation rate decreases to 90% during the 2nd hour; when dill oil is used alone the inactivation rate, which is 94.37% in the 1st hour, decreases to 94.37% during the 2nd hour.
- this rate starts at 90% in the 1 st hour and continues high until the 4th hour (98.22%). Therefore, if the two components are used together, it can successfully inactivate the viruses present in the medium.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Otolaryngology (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to an antiviral nasal spray for use in the healthcare sector. The antiviral nasal spray formulation, which is the subject of the invention, comprises natural ingredients that inactivate the virus and prevent it from multiplying without having a harmful effect on the cells.
Description
ANTIVIRAL NASAL SPRAY
Technical Field
The invention relates to an antiviral nasal spray for use in the healthcare sector and other pharmaceutical products that will be developed with the same active ingredients therefrom.
The invention particularly relates to a novel antiviral nasal spray that provides a high level of suppression against the virus by means of the active ingredient content of dill oil and tannic acid.
State of the Art
During the COVID-19 pandemic, millions of people were affected by this viral infection and hundreds of thousands of people lost their lives. As of October 2022, the total number of people diagnosed with Covid-19 was 16.9 million in Turkey and exceeded 623 million worldwide. In this period covering about 3 years, the number of cases that can be detected related to the number of deaths caused by COVID is around 101000 in Turkey and 65000000 worldwide. The incidence of pandemics has increased in the 20th and 21st century, along with outbreaks of SARS and MERS, which are of coronavirus origin like COVID-19, epidemics such as avian flu and swine flu, which are of influenza virus origin, lead to a significant level of threat and loss of life. In an important part of these diseases, the respiratory system (nasal tract) comes to the fore as a transmission route. Viruses that are the causative agents of the disease, after entering the body through the respiratory air, mainly cling to the nasal mucosa and initiate infection. The virus that multiplies here then either goes to the lungs and causes pneumonia, or spreads through the blood to the body, leading to a systemic (general) disease situation. When it comes to these advanced stages where the signs of the disease appear, the treatment options and chances of success for viral infections decrease significantly. Therefore, the most appropriate way to prevent or reduce the damage caused by such infections is to stop the virus at the point of entry into the body, which is still the initial stage of infection, that is, in the nasal mucosa.
The present practices followed for protection from viral infections transmitted through respiration and some of their deficiencies are given below:
The documents found in the patent and literature research conducted for the state of the art are summarized below.
US2019166903 A1 describes an apparatus for vaporizable liquid composition developed for personal use. However, there is no explanation for the combined use of dill oil and tannic acid in the said application.
WO2021206688 A1 relates to a compound developed for aromatherapy. However, there is no explanation for the combined use of dill oil and tannic acid in the said application.
Therefore, due to the disadvantages described above and due to the inadequacy of existing solutions on the subject, it became necessary to make an improvement in the relevant technical field.
Brief Description of the Invention
The present invention relates to an antiviral nasal spray that meets the requirements mentioned above, eliminates all the disadvantages, and provides some additional advantages.
The invention is inspired by the present situations and aims to solve the disadvantages mentioned above.
The main object of the invention is to develop a new formulation of antiviral nasal spray. The formulation, which is the subject of the invention, comprises natural ingredients that inactivate the virus and prevent it from multiplying without having a harmful effect on the cells. The main technical advantages of the antiviral nasal spray formulation are given below.
• By means of its active substance composition, it directly targets the virus and stops or reduces its reproduction. It has been shown in experimental laboratory studies that it has this property.
• It comprises completely natural active ingredients, for this reason, there is no risk of side and undesirable effects. The active ingredients used in its composition are obtained from products that are widely consumed as food. These products are consumed by millions of people every day. In addition, cytotoxicity experiments of the active substances contained in the formula have been performed and harmless doses have been determined in laboratory studies.
• Since it is applied in the form of a nasal spray, it stops the infection before it even starts or ends it by blocking it while it is still at the initial stage. In experiments conducted with the infective (live) coronavirus, the active ingredients in its formulation were found to block the virus both in its free state and to stop its entry into the cell and reproduction in the cell.
• It is prepared with easily available raw materials at a much lower cost compared to drug treatments. The dill oil and tannic acid substances contained in the formulation are easily available products and are differed from other active pharmaceutical ingredients in terms of price and logistics. There are no restrictions on national and international trade.
• By means of the supportive substances contained in the formulation, it supports antiviral activity for the following reasons:
Polyvinyl alcohol: Allows the active substance components to remain in the nasal mucosa for a longer time and effectively.
> Benzalkonium chloride: It has an anti- inflammation and decongestant effect.
> Phosphate buffer solution (pH 6.00): It is carriage substance of the formulation and increases the antimicrobial activity in the nasal mucosa by means of its adjusted pH.
The structural and characteristic features of the invention and all its advantages will be understood more clearly by means of the figures given below the detailed description written by making references to these figures, and therefore evaluation should be made taking into account these figures and detailed description.
Figures to Help Understand the Invention
In Figure 1 , effectiveness of dill oil on coronavirus is given versus time.
In Figure 2, effectiveness of tannic acid on coronavirus is given versus time.
In Figure 3, effectiveness of dill oil and tannic acid (together) on coronavirus is given versus time.
In Figure 4, the effect of dill oil and tannic acid with active ingredient supplementation is given on the reproduction of coronavirus at 48- hour intervals.
In Figure 5, cell adsorption and penetration rates are given.
In Figure 6, the effect of dill oil and tannic acid (together) is given on inactivating the coronavirus in the medium.
Detailed Description of the Invention
In this detailed description, the preferred embodiments of the invention are explained only for a better understanding of the subject.
The invention relates to an antiviral nasal spray for use in the healthcare sector. The formulation of the antiviral nasal spray contains dill oil and tannic acid as active ingredients, polyvinyl alcohol, benzalkonium chloride, phosphate buffer solution as auxiliary substances. The pH of the phosphate buffer solution is preferably 6. In the invention, dill oil and tannic acid are mandatory ingredients of antiviral nasal spray. Glycerin can be used instead of polyvinyl alcohol. Similarly, physiological saline can be used instead of phosphate buffer solution.
In a preferred application of the invention, the ingredients contained in the antiviral nasal spray formulation content, the intervals of use and the preferred amounts of use are given in the following table.
Dill oil is an herbal extract product comprising fatty acids with antiviral, antimicrobial and antioxidant activity. In experimental applications with coronavirus, it has been determined that it inactivates viruses in the medium at a rate of more than 98% for 4 hours, suppresses the entry of the virus into cells at a rate of more than 90%, and its reproduction in the cell at a rate of 99.58%.
Tannic acid is a compound with antiviral and antimicrobial activity and is found naturally in various plants. In experimental applications with coronavirus, it has been determined that it inactivates viruses in the medium at a rate of more than 98.2% for 4 hours, suppresses the entry of the virus into cells at a rate of more than 58%, and its reproduction in the cell at a rate of up to 100%.
In the studies carried out within the scope of the invention, it was determined that dill oil and tannic acid have a synergetic effect when used together and inactivate the coronavirus in the medium by 99.4%; suppress the entry of the virus into cells by more than 99.58% and the reproduction of the virus in the cell by up to 99.94%. For this reason, it has been evaluated that it would be appropriate to formulate both active substances together in the determined amounts.
Polyvinyl alcohol, by means of its structural property, allows the active substance components to remain in the nasal mucosa for a longer time and effectively.
Benzalkonium chloride provides a supportive effect in reducing mucosa damage due to virus infection by means of its anti-inflammatory and decongestant effect.
Phosphate buffer solution (pH 6.00) essentially acts as a vehicle substance in the formulation, but it supports the physiological defense barrier of the nasal mucosa by means of its balanced pH value. The pH level has been selected as the level with the highest antimicrobial activity in the nasal mucosa. Antiviral effectiveness may decrease if this value is changed upwards.
The antiviral nasal spray, which is the subject of the invention, has been prepared for use in order to prevent the onset or progression of respiratory viral infections. Non-sick individuals can use it to protect themselves against the virus, while sick individuals can use it to slow the progression of the disease and reduce contagion. After emptying the contents in the nose, if any, spray is applied to both nasal cavities 1-2 times. This application should be performed 4
times a day at intervals of six hours. Due to its natural content, it can also be applied at shorter intervals when needed.
In the production method of antiviral nasal spray, which is the subject of the invention, firstly, phosphate buffer solution (PBS) is prepared. PBS is prepared without calcium, and it is sterilized. Preferably, it is started to be spinned in a magnetic mixer in a glass container. Dill oil (preferably at a rate of 0.006-0.015% (v/v)) is added to the prepared solution, followed by Tannic acid (preferably at a rate of 30-70 pM). The added T is in powder form. The next added ingredient is polyvinyl alcohol (preferably 7-14 mg/ml). In the next processing step, benzalkonium chloride (preferably 0.01-0.04mg/ml) is added. The resulting final product is mixed for 30 - 60 minutes at a speed of 200 rpm, preferably at room temperature. Then, it is passed through preferably 0.2 pm membrane filter and sterile filtration process is applied. The final processing step is the filling process. In this process, glass or plastic spray light-proof bottles are filled. In this method, mixing is performed at a temperature of 21-24 ID for 30-60 minutes, sterile filtration is performed at a temperature of 21-24 ID, storage is performed at a temperature of 21-24 ‘C.
The studies conducted to prove that the invention provides an unexpected / surprising effect are summarized below. These studies are aimed at providing information only and they do not have any restrictive meaning.
Abbreviations:
Dill oil : An herbal essential oil
Tannic acid : A powdered compound derived from plants
BCoV : Coronavirus used in the study (Bovine coronavirus)
The Effect of Dill Oil on Coronavirus Reproduction
Virus titers obtained in the treatment of dill oil (live virus numbers)
Virus inhibition rates obtained by dill oil treatment (%) (virus inactivation rate)
The effectiveness of dill oil on coronavirus versus time is given in Figure 1. The effective concentration of dill oil was confirmed by this conducted experiment.
The Effect of Tannic Acid on Coronavirus Reproduction Virus titers obtained in the treatment of tannic acid (live virus numbers)
The effectiveness of tannic acid on coronavirus versus time is given in Figure 2. The effective concentration of tannic acid was confirmed by this conducted experiment.
The Effect of Dill oil and Tannic Acid (Together) on Coronavirus Reproduction Virus titers obtained in the treatment of dill oil and tannic acid (together) (live virus numbers)
Virus inhibition rates obtained dill oil and tannic acid (together) treatment (%) (virus inactivation rate)
Figure 3 shows the effectiveness of dill oil and tannic acid (together) on coronavirus versus time. With this experiment, dill oil and tannic were combined and tested together at the concentrations determined previously to be the most effective. Thus, the synergetic effect was examined. Thus, inhibition was achieved at a rate of 99.94% at 48th hour. It was determined that this effect lasted as >99% for 72 hours and decreased to 97% at 72nd hour.
The Effect of Dill oil and Tannic Acid Together on Coronavirus Reproduction and with Active Ingredient Supplementation at 48-Hour Intervals Virus titers obtained in the treatment of dill oil and tannic acid (together) (live virus numbers)
Virus inhibition rates obtained dill oil and tannic acid (together) treatment (%) (virus inactivation rate)
Figure 4 shows the effect of dill oil and tannic acid on coronavirus reproduction together and with active ingredient supplementation at 48-hour intervals. With this experiment, the dill oil and tannic acid at the concentrations that were previously determined to be the most effective are combined its use with supplementing it at intervals of 48 hours has been tested. Thus, the maximum frequency of use (time interval) was evaluated. With this application, the activity that was 99.44% in the 24th hour could be extended until the 120th hour.
The Effect of Dill oil and Tannic acid (together) on the Penetration of Coronavirus
Inhibition rates:
Figure 5 shows the adsorption and penetration rates. In this experiment, the potential of dill oil and tannic acid to prevent the penetration of coronavirus into the cell in the medium was tested when they are used separately and together. According to the data obtained, while the adsorption was stopped by 68.38% when the T substance was used alone, it achieved 90% success when the D substance was used alone. However, when the two components are used together, this ratio increases to 98.58%. This is one of the most prominent unexpected findings of this study.
Figure 6 shows the effect of dill oil and tannic acid (together) on inactivating the coronavirus present in the medium. In this experiment, the potential of inactivating the coronavirus present in the medium was tested when dill oil and tannic acid are used separately and together. According to the data obtained, when tannic acid is used alone it inactivates the coronavirus at a rate of 99.43% in the 1st hour, the inactivation rate decreases to 90% during the 2nd hour; when dill oil is used alone the inactivation rate, which is 94.37% in the 1st hour, decreases to 94.37% during the 2nd hour. However, when the two components are used together, this rate starts at 90% in the 1 st hour and continues high until the 4th hour (98.22%). Therefore, if the two components are used together, it can successfully inactivate the viruses present in the medium.
Claims
1. An antiviral nasal spray formulation, characterized by comprising dill oil and tannic acid.
2. The antiviral nasal spray formulation according to claim 1 , characterized by comprising polyvinyl alcohol or glycerin.
3. The antiviral nasal spray formulation according to claim 1 , characterized by comprising benzalkonium chloride.
4. The antiviral nasal spray formulation according to claim 1 , characterized by comprising phosphate buffer solution or physiological saline.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2016067283A1 (en) * | 2014-10-30 | 2016-05-06 | Rice Howard | Virucidal compositions comprising tannins for nasal and pulmonary administration |
US20170087199A1 (en) * | 2016-02-10 | 2017-03-30 | Senomyx, Inc. | Compositions for delivering a cooling sensation |
WO2017058594A1 (en) * | 2015-10-01 | 2017-04-06 | Senomyx, Inc. | Compounds useful as modulators of trpm8 |
US20210236422A1 (en) * | 2020-01-30 | 2021-08-05 | David Hampson | Nasal spray formulation having epistaxis prevention properties |
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- 2023-05-05 WO PCT/TR2023/050419 patent/WO2024005747A1/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016067283A1 (en) * | 2014-10-30 | 2016-05-06 | Rice Howard | Virucidal compositions comprising tannins for nasal and pulmonary administration |
WO2017058594A1 (en) * | 2015-10-01 | 2017-04-06 | Senomyx, Inc. | Compounds useful as modulators of trpm8 |
US20170087199A1 (en) * | 2016-02-10 | 2017-03-30 | Senomyx, Inc. | Compositions for delivering a cooling sensation |
US20210236422A1 (en) * | 2020-01-30 | 2021-08-05 | David Hampson | Nasal spray formulation having epistaxis prevention properties |
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