WO2022024147A1 - Compositions of lactoferrin whey protein and jackfruit seed powder - Google Patents
Compositions of lactoferrin whey protein and jackfruit seed powder Download PDFInfo
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- WO2022024147A1 WO2022024147A1 PCT/IN2021/050741 IN2021050741W WO2022024147A1 WO 2022024147 A1 WO2022024147 A1 WO 2022024147A1 IN 2021050741 W IN2021050741 W IN 2021050741W WO 2022024147 A1 WO2022024147 A1 WO 2022024147A1
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- lactoferrin
- functional food
- sars
- whey protein
- seed powder
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/19—Dairy proteins
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- 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)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
- A61K38/018—Hydrolysed proteins; Derivatives thereof from animals from milk
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/178—Lectin superfamily, e.g. selectins
Definitions
- the present invention relates to compositions comprising Lactoferrin and / or whey protein isolate and Jackfmit seed powder as functional food products for prophylactic care against SARS-COV-2 and SARS COV genre vims infections. More particularly, the invention relates to functional food compositions comprising Lactoferrin and or whey protein isolate and Jackfmit seed powder and or Jacalin (lectin from Jackfmit seeds) as immunity booster in geriatric patients thereby providing preventive, palliative, therapeutic and prophylactic care against SARS-COV-2 and SARS COV related infections.
- Coronavimses are important human and animal pathogens that typically affect the respiratory tract of mammals, including humans, and lead to mild to severe respiratory tract infections.
- a novel coronavims was identified at the end of 2019, as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei province of China, which is rapidly spread throughout China resulting in an epidemic. This is followed by an increasing number of cases in other countries throughout the world, resulting in pandemic.
- World Health Organization in Febmary 2020, designated the disease as COVID-19, which stands for coronavims disease 2019.
- the vims that causes COVID-19 is designated as severe acute respiratory syndrome coronavims 2 (SARS-CoV-2).
- Drug repurposing of an approved drug for the treatment of COVID-19 is one line of scientific research which is currently being pursued worldwide to develop effective COVID-19 treatments.
- the other research directions include the development of COVID-19 vaccines and convalescent plasma transfusion.
- the human clinical trials currently being carried out on the drugs for repurposing for the treatment of COVID 19 include, certain phytochemicals, antimalarial drugs, antibacterial drugs, anticancer agents, ACE inhibitors, antiviral agents, anti-inflammatory agents, antacids, monoclonal antibodies etc.
- the Solidarity trial organized by the World Health Organization and partners announced 18 March 2020, is a multinational Phase III-IV clinical trial to compare the efficiency of the drug candidates under study for hospitalized people with severe COVID-19 illness. Over 100 countries are participating in this clinical trial.
- an effective treatment for SARS COV-2 / SARS COV/ SARS COV should address all these three aspects, or at least two of the three pathological conditions, to arrest the progression of the disease. While immune dysfunction and generation of inflammatory storm by up-regulation of inflammatory cytokine production are related, from the perspective of designing an effective therapy it would be ideal if all of these three aspects are modulated through the external medication.
- a treatment will be holistic if it were to restore the immune response (that can be assessed from the CD4+: CD8+ ratio), reduce the pro- inflammatory cytokines and inhibit the viral binding to human tissues.
- Ideal therapeutic target for a viral infection is the protein critical for infectivity, such as hemagglutinin (HA).
- HA a glycoprotein expressed on the viral envelope along with neuraminidase (NA)
- NA neuraminidase
- CD4+ helper/inducer cells and CD8+ cytotoxic/suppressor cells are 2 phenotypes of T lymphocytes, characterized by distinct surface markers and functions that mostly reside in lymph nodes but also circulate in the blood.
- the normal CD4+/CD8+ ratio in healthy hosts is poorly defined. Ratios between 1.5 and 2.5 are generally considered normal.
- a low or inverted CD4+/CD8+ ratio is an immune risk phenotype and is associated with altered immune function, immune senescence, and chronic infl mmation.
- HIV HIV, SARS
- CD4+/CD8+ ratio more accurately describes this overall immune dysfunction and hence could be considered as a better biomarker for disease progression, response to treatment, morbidity, and mortality for the virally suppressed people.
- Lactoferrin (Lf), a 80-kDa multifunctional cationic iron binding glycoprotein belonging to the transferrin family, is known to specifically bind to the HA2 subunit of HA of SARS vims. Lf in addition co-localizes with the widely distributed cell-surface heparan sulfate proteoglycans (HSPGs). HSPGs (along with ACE) are required for the SARS CoV-2 / SARS COVto bind to human tissues. Thus, in totality Lf will interfere with SARS CoV-2 / SARS COVbinding to human (lung) tissues.
- HSPGs heparan sulfate proteoglycans
- Lactoferrin specifically bovine lactoferrin (bLf) is more active than human lactoferrin and is listed as a GRAS molecule by US FDA.
- Lf is a part of human immune system, persons with low immunity, have lower amounts of Lf, hence, the person with lower Lf levels contract SARS CoV-2 / SARS COVvery easily. Therefore, replenishing Lf (bLf) by external intake will aid in improving the immunity, thereby dislodging the SARS CoV-2 / SARS COVfrom the tissues, thus providing instant relief to COVID patients.
- Whey protein isolate contains 1 - 2% of lactoferrin, while colostrum contains about 7 - 9 % of lactoferrin. Instead of using lactoferrin, we can also use whey protein isolate of colostrum.
- Jackfmit ( Artocarpus heterophyllus) is a species of tree in the mulberry family (Moraceae), which grow abundantly in India, Bangladesh, and in many parts of Southeast Asia.
- Jackfmit seeds have several nutrients, which are beneficial for the body.
- the seeds contain a right amount of starch, protein, vitamins, minerals and antioxidants. Apart from this, jackfmit seeds contain approximately 40% carbohydrates, 7.5 % protein and 3% fibre with about 50% moisture. Also, riboflavin, thiamine, magnesium, phosphorus, etc., are found in abundance in jackfmit seeds. Jackfmit seeds can be beneficial for diarrhoea patients as they contain antibacterial properties.
- the seeds of jackfmit are special antioxidants, which also protect a person from the risk of cancer. These antioxidants, which are prominently present in this fruit, are flavonoids, saponins and phenolics.
- Jacalin a 65-kDa protein isolated from seeds of a tropical plant, jackfmit, has a strong affinity for galactose b1®3 linked to N- acetylgalactosamine (Kabir, 1998).
- Lectin, jacalin, from jackfmit seeds Artocarpus integrifolia ), have been known to be mitogenic for CD4++ and interacting with lymphocyte cell-surface molecule CD4+, a known receptor for the human immunodeficiency virus type 1 (HIV-1).
- Jack Fruit lectin was found to show an inhibitory activity with cytopathic effect (CPE) towards herpes simplex virus type 2 (HSV-2), varicellar-zoster (VZV) and cytomegalovirus (CMV). It is reported that JFL is mitogenic for NK lymphocyte (CD16+/CD56+ and also active against HSV-2, VZV and CMV (Japanese Journal oflnfectious Disease. 2000 Aug;53(4): 156-61).
- CPE cytopathic effect
- HSV-2 herpes simplex virus type 2
- VZV varicellar-zoster
- CMV cytomegalovirus
- Jack fruit seed proteases inhibit blood clotting and are effective in the treatment of thrombotic disorders. Blood clotting has been shown as one of the morbidities in SARS COV-2 / SARS COVinfection. Further, presence of substantial amounts of nutritive polyphenols in jackfruit seed powder, will provide the anti-oxidant effect.
- Jackfruit seed powder will modulate the innate immune function, inhibit blood clotting, reduce inflammation and finally due to the high polyphenol content will also reduce reactive oxygen species.
- the present invention provides functional food compositions comprising combination of Lactoferrin (which interferes with viral binding to human tissues) and/ or whey protein (isolate) and / or colostrum and jackfmit seed powder and / or Jacalin (which restores the innate immunity and reduces the inflammation) in therapeutically effective amounts for the prevention and treatment of COVID-19.
- the invention provides a functional food compositions comprising combination of Lactoferrin and jackfmit seed powder in therapeutically effective amounts optionally in association with nutraceutical excipients, for the prevention and treatmentof COVID-19.
- the lactoferrin as used in the present invention may be selected from bovine lactoferrin, caprine lactoferrin, colostmm or whey protein, or whey protein isolates containing lactoferrin.
- the functional food compositions comprises lmg to 40mg of Bovine or caprine Lactoferin and / or whey protein isolate and/or colostmm and Jack fruit seed powder/flour in an amount of 250mg to 500mgalong with suitable carriers/excipients that can be administered per day in a single dose or in divided doses.
- the invention provides functional food compositions comprising Bovine Lactoferrin and / or whey protein / whey protein isolate / colostrum and Jackfmit seed powder / flour in 1 : 1 to 10, 1 to 10:1 weight ratios as immunity booster in geriatric patients so as to prevent morbidity due to SARS-COV-2 / SARS COV.
- the invention provides a functional food compositions comprising Bovine or caprine Lactoferrin and / or whey protein isolate / colostrum and Jackfmit seed powder as immunity booster in patients during convalescence (recuperation).
- the invention provides methods for treating or preventing COVID-19or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food composition comprising lactoferrin and jackfmit seed powder in therapeutically effective amounts to alleviate the vims load of SARS CoV-2 / SARS COVfrom the subject suffering from COVID- 19 and to boost the immunity of the subject.
- the invention provides methods for treating or preventing COVID-19 or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food composition comprising lactoferrin and / or whey protein isolate / colostmm and jackfmit seed powder in therapeutically effective amounts to substantially eliminate symptoms associated with the viral load of SARS CoV-2 / SARS COV / SARS COV and to boost the immunity of the subject.
- a functional food composition comprising lactoferrin and / or whey protein isolate / colostmm and jackfmit seed powder in therapeutically effective amounts to substantially eliminate symptoms associated with the viral load of SARS CoV-2 / SARS COV / SARS COV and to boost the immunity of the subject.
- the present invention provides use of the a functional food composition comprising lactoferrin and/ or whey protein isolate / colostrum and jackfmit seed powder in therapeutically effective amounts to alleviate the vims load of SARS CoV-2 / SARS COV from a subject suffering from COVID-19 and to boost the immunity of the subject.
- Figure 1 shows In vitro Therapeutic activity of AIPL - 001 on SARS COV2
- Figure 2 shows In-vitro therapeutic activity of AIPL-012 formulation
- Figure 3 shows EC50 values of AIPL-012formulation
- the present invention provides functional food compositions comprising combination of Lactoferrin (which interferes with viral binding to human tissues) and/ or whey protein isolate / colostrum and jackfmit seed powder (which restores the innate immunity and reduces the inflammation) in therapeutically effective amounts for the prevention and treatment of COVID-19.
- the lactoferrin as used in the present invention may be selected from bovine lactoferrin or whey protein isolates or colostrum containing lactoferrin.
- the invention provides a functional food compositions comprising combination of Bovine Lactoferrin and jackfmit seed powder in therapeutically effective amounts optionally in association with suitable nutraceutical excipients/carriers, for the prevention and treatment of COVID-19.
- the functional food compositions according to the present invention include various functional food formulations.
- nutraceutical excipients/carriers that can be used in the preparation of functional food formulations are selected from the group consisting of controlled release binders, diluents, lubricants, emulsifiers, oily vehicles, colorants, flavoring agents, sweeteners, bioadhesive agents, pH modifiers, controller release polymers, viscosity modifiers, stabilizers, surfactants and cosurfactants, plasticizers, food based carriers, preservatives, and the like.
- the functional food compositions of the present invention may be formulated into a dosage form selected from dry powder form, liquid form, beverage, food product, dietary supplement or any suitable form such as tablet, a capsule or a soft chewable or gummy bar.
- the functional food formulations as disclosed above include nutritional/dietary supplements that can be contemplated/made into the dosage form of healthy foods, or food for specified health uses such as solid food like cereal, snack bar, chocolate or nutritional bars, drop, candy, chewing gum, gummy candy, cream, jam, pudding, jelly or cookie and beverages.
- the functional food formulation may include a food-based carrier which is defined as food or is derived from food.
- food- based carriers include saccharide or polysaccharide syrups such as sucrose syrup, honey, date syrup, fruit syrups such as maple syrup.
- saccharide or polysaccharide syrups such as sucrose syrup, honey, date syrup, fruit syrups such as maple syrup.
- the preferred food based carriers that can be used in the functional food formulations that naturally include a high nutrient content as well as beneficial elements such as vitamins and minerals.
- the functional food compositions comprises lOmg to 4000mg of Bovine Lactoferin and Jack fruit seed powder in an amount of lOmg to 500mg optionally with suitable carriers/excipients that can be administered per day in a single dose or in divided doses.
- the treatment regimen may be decided by the physicians/practitioners based on the recovery of the patient to the treatment.
- functional food compositions comprises lOOmg to 4000mg of Bovine Lactoferin and Jack fruit seed powder in an amount of 250mg to 500mg optionally with suitable carriers/ excipients
- the functional food compositions may be formulated into various dosage forms such as solid and liquid dosage forms selected from the group consisting of tablets, capsules, powders, granules, liquids, solutions and suspensions.
- the invention provides a functional food composition
- a functional food composition comprising Bovine Lactoferrin and Jackfruit seed powder as immunity booster in paediatric and geriatric population so as to prevent morbidity due to SARS-COV-2.
- the invention provides a functional food composition comprising Bovine Lactoferrin and Jackfruit seed powder as immunity booster in patients during convalescence (recuperation).
- the invention provides methods for treating or preventing COVID-19 or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food compositions comprising lactoferrin and jackfruit seed powder in therapeutically effective amounts to substantially eliminate the virus load of SARS CoV-2 / SARS COVfrom the subject suffering from COVID-19 and to boost the immunity of the said subject.
- the invention provides methods for treating or preventing COVID-19 or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food compositions comprising lactoferrin and jackfruit seed powder in therapeutically effective amounts to substantially alleviate the symptoms associated with the viral load of SARS CoV-2 / SARS COVand to boost the immunity of the subject.
- the present invention comprises use of a functional food composition comprising lactoferrin and jackfruit seed powder in therapeutically effective amounts to eliminate the virus load of SARS CoV-2 / SARS COV from the subject suffering from COVID- 19 and further to boost the immunity of the said subject.
- the invention provides functional food compositionsthat can be prepared by employing whey protein isolate instead of lactoferrin.
- Whey protein isolate contains therapeutically active amounts of lactoferrin along with a whole lot of other bioactive ingredients (composition is given in Table-1).
- the functional food composition comprising a combination of whey protein isolates (WPI) and jackfmit seed powder (JSP) in therapeutically effective amounts that will provide adequate immune protection to fight viral infections.
- the functional food composition comprising whey protein isolate and or Whey protein with jackfmit seed powder, may be prepared with varying proportions of WPI and JSP in a ratio of 1 : 99 to 99: 1.
- the functional food compositions comprising WPI and JSP can be formulated into Nutrition bar; Health drink powder; Extruded products; Gummies and chewable, snack bar, chocolate, candy, cookies, etc.
- the invention provides methods for treating or preventing COVED- 19 or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food composition comprising a combination of whey protein isolates (WPI) and jackfruit seed powder (JSP) in therapeutically effective amounts to substantially alleviate symptoms associated with the viral load of SARS CoV-2 / SARS COVand further to boost the immunity of the said subject.
- a functional food composition comprising a combination of whey protein isolates (WPI) and jackfruit seed powder (JSP) in therapeutically effective amounts to substantially alleviate symptoms associated with the viral load of SARS CoV-2 / SARS COVand further to boost the immunity of the said subject.
- WPI whey protein isolates
- JSP jackfruit seed powder
- the present invention comprises use of a functional food composition comprising a combination of whey protein isolates (WPI) and jackfruit seed powder (JSP) in therapeutically effective amounts to eliminate the virus load of SARS CoV-2 / SARS COVfrom the subject suffering from COVID-19 and further to boost the immunity of the said subject.
- WPI whey protein isolates
- JSP jackfruit seed powder
- the invention provides a functional food composition comprising a combination of whey protein isolates (WPI) and Jackfruit seed powder as immunity booster in paediatric and geriatric population so as to prevent morbidity due to SARS-COV-2.
- the invention provides a functional food composition comprising a combination of whey protein isolates (WPI) and Jackfmit seed powder as immunity booster in patients during convalescence (recuperation).
- test compound Different dilutions of test compound were added on Vero cell monolayer in triplicate and these plates were incubated at 37 °C in 5% C02. After incubation, development solution was added to the cells followed by incubated at 37 °C in 5% C02. The absorbance was taken. This process was repeated until exact value for MNTD and CC50 is derived. The time period required for determination of final MNTD and CC50 value was about 2-3 weeks.
- EC50 Compound concentration required to achieve 50 % protection from virus-induced cytopathogenicity.
- CC50 Compound concentration required to reduce cell viability by 50%.
- SI* selectiveivity index
- Vimcidal activity determination Based on the MNTD and CC50 value, 6 different concentrations of each drug were accessed for its virucidal effect in triplicate, by incubatingwith SARS-CoV-2 vims. Accordingly, virus-test compound mixture was added to the Vero cell monolayer for infection. These plates were then incubated at 37 °C in 5% C02. After incubation, quantitative CPE based score were made for EC50 determination.
- Therapeutic mode Based on the MNTD and CC50 value, 6 different concentrations of each drug were accessed for its virucidal effect in triplicate, by incubatingwith SARS-CoV-2 vims. Accordingly, virus-test compound mixture was added to the Vero cell monolayer for infection. These plates were then incubated at 37 °C in 5% C02. After incubation, quantitative CPE based score were made for EC50 determination.
- Therapeutic mode Based on the MNTD and CC50 value, 6 different concentrations of each drug were accessed for its virucidal effect
- AIPL-SC- 001 is Lactoferrin, AIPL-SC- 012, is Jacalin.
- In-vitro therapeutic activity of AIPL-001 and AIPL-012 formulations are shown in figure 1 and 2. It is evident from figures 1 lactoferrin is more potent in higher concentrations. However, high therapeutic activity of Jacalin /Jack fruit seed powder exhibits more potent in lower concentrations initially and probably acting on the TMPRSS or Furin (ineffective on MLPro & CL Pro).
- the combination of lactoferrin and Jacalin provides synergistic effect, when compared to individual ingredients.
- the SI values (Therapeutic mode) of all the examples 1 to 4 shows synergy among the constituents of the formulations.
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Abstract
The present invention discloses compositions comprising Lactoferrin or whey protein isolate and Jackfruit seed powder as functional food products for prophylactic and or therapeutic care against SARS-COV-2 & SARS COV infections. More particularly, the invention discloses compositions comprising Lactoferrin and or whey protein isolate and Jackfruit seed powder and or Jacalin as immunity booster in general and specifically in geriatric conditions thereby providing preventive, therapeutic and prophylactic care against SARS-COV-2 and SARS COV infections.
Description
“COMPOSITIONS OF LACTOFERRIN WHEY PROTEIN AND
JACKFRUIT SEED POWDER”
Technical filed:
The present invention relates to compositions comprising Lactoferrin and / or whey protein isolate and Jackfmit seed powder as functional food products for prophylactic care against SARS-COV-2 and SARS COV genre vims infections. More particularly, the invention relates to functional food compositions comprising Lactoferrin and or whey protein isolate and Jackfmit seed powder and or Jacalin (lectin from Jackfmit seeds) as immunity booster in geriatric patients thereby providing preventive, palliative, therapeutic and prophylactic care against SARS-COV-2 and SARS COV related infections.
Background and prior art:
Coronavimses are important human and animal pathogens that typically affect the respiratory tract of mammals, including humans, and lead to mild to severe respiratory tract infections. A novel coronavims was identified at the end of 2019, as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China, which is rapidly spread throughout China resulting in an epidemic. This is followed by an increasing number of cases in other countries throughout the world, resulting in pandemic. World Health Organization, in Febmary 2020, designated the disease as COVID-19, which stands for coronavims disease 2019. The vims that causes COVID-19 is designated as severe acute respiratory syndrome coronavims 2 (SARS-CoV-2).
Drug repurposing of an approved drug for the treatment of COVID-19 is one line of scientific research which is currently being pursued worldwide to develop effective COVID-19 treatments. The other research directions include the development of COVID-19 vaccines and convalescent plasma transfusion. The human clinical trials currently being carried out on the drugs for repurposing for the treatment of COVID 19 include, certain phytochemicals, antimalarial drugs, antibacterial drugs, anticancer agents, ACE inhibitors, antiviral agents, anti-inflammatory agents, antacids, monoclonal antibodies etc. The Solidarity trial organized by the World Health Organization and partners announced 18 March 2020, is a multinational Phase III-IV clinical trial to compare the efficiency of the drug candidates under study for hospitalized people with severe COVID-19 illness. Over 100 countries are participating in this clinical trial.
SARS COV-2 / SARS COV& SARS CO V Viral infection leads to three major pathological effects - Immune dysfunction (CD4+ / CD8+ ratio disruption) Morbidities associated due to viral penetration into various human tissues Production of Inflammatory storm
Therefore, an effective treatment for SARS COV-2 / SARS COV/ SARS COV should address all these three aspects, or at least two of the three pathological conditions, to arrest the progression of the disease. While immune dysfunction and generation of inflammatory storm by
up-regulation of inflammatory cytokine production are related, from the perspective of designing an effective therapy it would be ideal if all of these three aspects are modulated through the external medication. A treatment will be holistic if it were to restore the immune response (that can be assessed from the CD4+: CD8+ ratio), reduce the pro- inflammatory cytokines and inhibit the viral binding to human tissues. Ideal therapeutic target for a viral infection is the protein critical for infectivity, such as hemagglutinin (HA). HA, a glycoprotein expressed on the viral envelope along with neuraminidase (NA), is pivotal for the interactions between the influenza virus and sialic acid side chains of receptors on the host cell surface and is also required for the final step of viral entry into susceptible cells. Inhibiting HA can result in two outcomes:
(i) prevention of the interaction between viral surface proteins and cell surface receptors;
(ii) blocking of viral envelope fusion with the host cell membrane and thereby the release of viral nucleoproteins into the cytoplasm.
Strategies for correcting the immune dysfunction (restore the ratio of CD4+/ CD8+ to 2):
CD4+ helper/inducer cells and CD8+ cytotoxic/suppressor cells are 2 phenotypes of T lymphocytes, characterized by distinct surface markers and functions that mostly reside in lymph nodes but also circulate in the blood. The normal CD4+/CD8+ ratio in healthy hosts is poorly defined. Ratios between 1.5 and 2.5 are generally considered normal. A low or
inverted CD4+/CD8+ ratio is an immune risk phenotype and is associated with altered immune function, immune senescence, and chronic infl mmation.
The immunopathology of viral infection (HIV, SARS) is more consistent with immune dysfunction than immune suppression alone. The CD4+/CD8+ ratio more accurately describes this overall immune dysfunction and hence could be considered as a better biomarker for disease progression, response to treatment, morbidity, and mortality for the virally suppressed people.
Lactoferrin (Lf), a 80-kDa multifunctional cationic iron binding glycoprotein belonging to the transferrin family, is known to specifically bind to the HA2 subunit of HA of SARS vims. Lf in addition co-localizes with the widely distributed cell-surface heparan sulfate proteoglycans (HSPGs). HSPGs (along with ACE) are required for the SARS CoV-2 / SARS COVto bind to human tissues. Thus, in totality Lf will interfere with SARS CoV-2 / SARS COVbinding to human (lung) tissues.
Lactoferrin, specifically bovine lactoferrin (bLf) is more active than human lactoferrin and is listed as a GRAS molecule by US FDA. Lf is a part of human immune system, persons with low immunity, have lower amounts of Lf, hence, the person with lower Lf levels contract SARS CoV-2 / SARS COVvery easily. Therefore, replenishing Lf (bLf) by external intake will aid in improving the immunity, thereby
dislodging the SARS CoV-2 / SARS COVfrom the tissues, thus providing instant relief to COVID patients. Whey protein isolate contains 1 - 2% of lactoferrin, while colostrum contains about 7 - 9 % of lactoferrin. Instead of using lactoferrin, we can also use whey protein isolate of colostrum.
Jackfmit ( Artocarpus heterophyllus) is a species of tree in the mulberry family (Moraceae), which grow abundantly in India, Bangladesh, and in many parts of Southeast Asia.
Jackfmit seeds have several nutrients, which are beneficial for the body. The seeds contain a right amount of starch, protein, vitamins, minerals and antioxidants. Apart from this, jackfmit seeds contain approximately 40% carbohydrates, 7.5 % protein and 3% fibre with about 50% moisture. Also, riboflavin, thiamine, magnesium, phosphorus, etc., are found in abundance in jackfmit seeds. Jackfmit seeds can be beneficial for diarrhoea patients as they contain antibacterial properties. The seeds of jackfmit are special antioxidants, which also protect a person from the risk of cancer. These antioxidants, which are prominently present in this fruit, are flavonoids, saponins and phenolics.
Jacalin, a 65-kDa protein isolated from seeds of a tropical plant, jackfmit, has a strong affinity for galactose b1®3 linked to N- acetylgalactosamine (Kabir, 1998). Lectin, jacalin, from jackfmit seeds ( Artocarpus integrifolia ), have been known to be mitogenic for CD4++ and interacting with lymphocyte cell-surface molecule CD4+, a known
receptor for the human immunodeficiency virus type 1 (HIV-1). Jack Fruit lectin (JFL) was found to show an inhibitory activity with cytopathic effect (CPE) towards herpes simplex virus type 2 (HSV-2), varicellar-zoster (VZV) and cytomegalovirus (CMV). It is reported that JFL is mitogenic for NK lymphocyte (CD16+/CD56+ and also active against HSV-2, VZV and CMV (Japanese Journal oflnfectious Disease. 2000 Aug;53(4): 156-61).
In addition, Jack fruit seed proteases inhibit blood clotting and are effective in the treatment of thrombotic disorders. Blood clotting has been shown as one of the morbidities in SARS COV-2 / SARS COVinfection. Further, presence of substantial amounts of nutritive polyphenols in jackfruit seed powder, will provide the anti-oxidant effect.
Therefore, Jackfruit seed powder will modulate the innate immune function, inhibit blood clotting, reduce inflammation and finally due to the high polyphenol content will also reduce reactive oxygen species.
Accordingly, it is an objective of the present invention to provide functional food compositions comprising a combination of Lactoferrin (which interferes with viral binding to human tissues) and/ or whey protein isolate and/or colostrum and jackfruit seed powder (which restores the innate immunity and reduces the inflammation) in therapeutically effective amounts for the prevention and treatment of COVID-19.
Summary of the invention:
In line with the above, the present invention provides functional food compositions comprising combination of Lactoferrin (which interferes with viral binding to human tissues) and/ or whey protein (isolate) and / or colostrum and jackfmit seed powder and / or Jacalin (which restores the innate immunity and reduces the inflammation) in therapeutically effective amounts for the prevention and treatment of COVID-19.
In another aspect, the invention provides a functional food compositions comprising combination of Lactoferrin and jackfmit seed powder in therapeutically effective amounts optionally in association with nutraceutical excipients, for the prevention and treatmentof COVID-19.
The lactoferrin as used in the present invention may be selected from bovine lactoferrin, caprine lactoferrin, colostmm or whey protein, or whey protein isolates containing lactoferrin.
In a further aspect, the functional food compositions comprises lmg to 40mg of Bovine or caprine Lactoferin and / or whey protein isolate and/or colostmm and Jack fruit seed powder/flour in an amount of 250mg to 500mgalong with suitable carriers/excipients that can be administered per day in a single dose or in divided doses.
In yet another aspect, the invention provides functional food compositions comprising Bovine Lactoferrin and / or whey protein / whey protein isolate / colostrum and Jackfmit seed powder / flour in 1 : 1 to 10, 1 to 10:1 weight ratios as immunity booster in geriatric patients so as to prevent morbidity due to SARS-COV-2 / SARS COV.
In yet another aspect, the invention provides a functional food compositions comprising Bovine or caprine Lactoferrin and / or whey protein isolate / colostrum and Jackfmit seed powder as immunity booster in patients during convalescence (recuperation).
In yet another aspect, the invention provides methods for treating or preventing COVID-19or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food composition comprising lactoferrin and jackfmit seed powder in therapeutically effective amounts to alleviate the vims load of SARS CoV-2 / SARS COVfrom the subject suffering from COVID- 19 and to boost the immunity of the subject.
In yet another aspect, the invention provides methods for treating or preventing COVID-19 or symptoms associated with COVID-19 in a subject which method comprises administering the subject witha functional food composition comprising lactoferrin and / or whey protein isolate / colostmm and jackfmit seed powder in therapeutically effective amounts to substantially eliminate symptoms associated with
the viral load of SARS CoV-2 / SARS COV / SARS COV and to boost the immunity of the subject.
In yet another aspect, the present invention provides use of the a functional food composition comprising lactoferrin and/ or whey protein isolate / colostrum and jackfmit seed powder in therapeutically effective amounts to alleviate the vims load of SARS CoV-2 / SARS COV from a subject suffering from COVID-19 and to boost the immunity of the subject.
Description of drawings:
Figure 1 shows In vitro Therapeutic activity of AIPL - 001 on SARS COV2
Figure 2 shows In-vitro therapeutic activity of AIPL-012 formulation Figure 3 shows EC50 values of AIPL-012formulation
Detailed description of the invention:
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.
Today, consumers are armed with health information at their fingertips, giving them the ability to analyse and decide for themselves from a dietary aspect which prevention techniques can help them achieve a greater sense of wellness without having toxic side effects.
Accordingly, the present invention provides functional food compositions comprising combination of Lactoferrin (which interferes with viral binding to human tissues) and/ or whey protein isolate / colostrum and jackfmit seed powder (which restores the innate immunity and reduces the inflammation) in therapeutically effective amounts for the prevention and treatment of COVID-19.
The lactoferrin as used in the present invention may be selected from bovine lactoferrin or whey protein isolates or colostrum containing lactoferrin.
In another embodiment, the invention provides a functional food compositions comprising combination of Bovine Lactoferrin and jackfmit seed powder in therapeutically effective amounts optionally in association with suitable nutraceutical excipients/carriers, for the prevention and treatment of COVID-19.
In an embodiment, the functional food compositions according to the present invention include various functional food formulations.
The nutraceutical excipients/carriers that can be used in the preparation of functional food formulations are selected from the group consisting of controlled release binders, diluents, lubricants, emulsifiers, oily vehicles, colorants, flavoring agents, sweeteners, bioadhesive agents, pH modifiers, controller release polymers, viscosity modifiers,
stabilizers, surfactants and cosurfactants, plasticizers, food based carriers, preservatives, and the like.
In another embodiment, the functional food compositions of the present invention may be formulated into a dosage form selected from dry powder form, liquid form, beverage, food product, dietary supplement or any suitable form such as tablet, a capsule or a soft chewable or gummy bar.
In another embodiment of the invention, the functional food formulations as disclosed above include nutritional/dietary supplements that can be contemplated/made into the dosage form of healthy foods, or food for specified health uses such as solid food like cereal, snack bar, chocolate or nutritional bars, drop, candy, chewing gum, gummy candy, cream, jam, pudding, jelly or cookie and beverages.
The functional food formulation may include a food-based carrier which is defined as food or is derived from food. For example, food- based carriers include saccharide or polysaccharide syrups such as sucrose syrup, honey, date syrup, fruit syrups such as maple syrup. The preferred food based carriers that can be used in the functional food formulations that naturally include a high nutrient content as well as beneficial elements such as vitamins and minerals.
In a further embodiment, the functional food compositions comprises lOmg to 4000mg of Bovine Lactoferin and Jack fruit seed powder in an
amount of lOmg to 500mg optionally with suitable carriers/excipients that can be administered per day in a single dose or in divided doses. The treatment regimen may be decided by the physicians/practitioners based on the recovery of the patient to the treatment.
In a preferred embodiment, functional food compositions comprises lOOmg to 4000mg of Bovine Lactoferin and Jack fruit seed powder in an amount of 250mg to 500mg optionally with suitable carriers/ excipients
The functional food compositions may be formulated into various dosage forms such as solid and liquid dosage forms selected from the group consisting of tablets, capsules, powders, granules, liquids, solutions and suspensions.
In yet another aspect, the invention provides a functional food composition comprising Bovine Lactoferrin and Jackfruit seed powder as immunity booster in paediatric and geriatric population so as to prevent morbidity due to SARS-COV-2.
In yet another aspect, the invention provides a functional food composition comprising Bovine Lactoferrin and Jackfruit seed powder as immunity booster in patients during convalescence (recuperation).
In yet another aspect, the invention provides methods for treating or preventing COVID-19 or symptoms associated with COVID-19 in a
subject which method comprises administering the subject with a functional food compositions comprising lactoferrin and jackfruit seed powder in therapeutically effective amounts to substantially eliminate the virus load of SARS CoV-2 / SARS COVfrom the subject suffering from COVID-19 and to boost the immunity of the said subject.
In yet another aspect, the invention provides methods for treating or preventing COVID-19 or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food compositions comprising lactoferrin and jackfruit seed powder in therapeutically effective amounts to substantially alleviate the symptoms associated with the viral load of SARS CoV-2 / SARS COVand to boost the immunity of the subject.
In yet another aspect, the present invention comprises use of a functional food composition comprising lactoferrin and jackfruit seed powder in therapeutically effective amounts to eliminate the virus load of SARS CoV-2 / SARS COV from the subject suffering from COVID- 19 and further to boost the immunity of the said subject.
In an alternate embodiment, the invention provides functional food compositionsthat can be prepared by employing whey protein isolate instead of lactoferrin.
Whey protein isolate contains therapeutically active amounts of lactoferrin along with a whole lot of other bioactive ingredients (composition is given in Table-1).
Accordingly, in an alternate embodiment, the functional food compositioncomprising a combination of whey protein isolates (WPI) and jackfmit seed powder (JSP) in therapeutically effective amounts that will provide adequate immune protection to fight viral infections. The functional food composition comprising whey protein isolate and or Whey protein with jackfmit seed powder, may be prepared with varying proportions of WPI and JSP in a ratio of 1 : 99 to 99: 1.
The functional food compositions comprising WPI and JSP can be formulated into Nutrition bar; Health drink powder; Extruded products; Gummies and chewable, snack bar, chocolate, candy, cookies, etc.
In yet another embodiment, the invention provides methods for treating or preventing COVED- 19 or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food composition comprising a combination of whey protein isolates (WPI) and jackfruit seed powder (JSP) in therapeutically effective amounts to substantially alleviate symptoms associated with the viral load of SARS CoV-2 / SARS COVand further to boost the immunity of the said subject.
In yet another embodiment, the present invention comprises use of a functional food composition comprising a combination of whey protein isolates (WPI) and jackfruit seed powder (JSP) in therapeutically effective amounts to eliminate the virus load of SARS CoV-2 / SARS COVfrom the subject suffering from COVID-19 and further to boost the immunity of the said subject.
In yet another embodiment, the invention provides a functional food composition comprising a combination of whey protein isolates (WPI) and Jackfruit seed powder as immunity booster in paediatric and geriatric population so as to prevent morbidity due to SARS-COV-2.
In yet another embodiment, the invention provides a functional food composition comprising a combination of whey protein isolates (WPI) and Jackfmit seed powder as immunity booster in patients during convalescence (recuperation).
Those of ordinary skilled in the art will appreciate that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the particular embodiments or examples disclosed herein, but is intended to cover modifications within the objectives and scope of the present invention as defined in the specification. The presented examples illustrate the invention, but they should not be considered to limit the scope of the invention in any way.
Examples:
Example 1:
Example 2
Example 3
Example 4
Example 5:
Assay procedure:
The Assay of the molecular complex of Lactoferrin and combination of Lactoferrin and Jack fruit seed powder; was conducted for determining CC50 and MNTD (Maximum non-toxic dose).
Procedure for MNTD and CC50 determination:
Different dilutions of test compound were added on Vero cell monolayer in triplicate and these plates were incubated at 37 °C in 5% C02. After incubation, development solution was added to the cells
followed by incubated at 37 °C in 5% C02. The absorbance was taken. This process was repeated until exact value for MNTD and CC50 is derived. The time period required for determination of final MNTD and CC50 value was about 2-3 weeks.
EC50: Compound concentration required to achieve 50 % protection from virus-induced cytopathogenicity.
CC50: Compound concentration required to reduce cell viability by 50%.
SI* (selectivity index): ratio by CC50/EC50.
*The higher SI ratio = theoretically more effective and safe drug during in vivo treatment for a given viral infection.
Example 3
In vitro antiviral activity determination of formulation against SARS- CoV-2 vims. This process was conducted in two modes viz., Prophylactic mode and Therapeutic mode.
A. Prophylactic mode:
In this method; based on the MNTD and CC50 value, 6 different concentrations of each drug will be accessed for antiviral potency at 4 different time points in triplicate. Accordingly, the Cells were washed and infected with SARS CoV-2 / SARS COVvims. These plates were incubated at 37 °C in 5% C02. After incubation period, quantitative CPE based score were made for EC50 determination.
Vimcidal activity determination:
Based on the MNTD and CC50 value, 6 different concentrations of each drug were accessed for its virucidal effect in triplicate, by incubatingwith SARS-CoV-2 vims. Accordingly, virus-test compound mixture was added to the Vero cell monolayer for infection. These plates were then incubated at 37 °C in 5% C02. After incubation, quantitative CPE based score were made for EC50 determination. Therapeutic mode:
In this method, based on the MNTD and CC50 value, 6 different concentrations of each dmg were assessed for antiviral potency at 4 different time points in triplicate. This experiment will determine therapeutic potential of dmg at different stage of the vims life cycle (assembly, internalization and replication stage). Accordingly, Vero cells were infected with SARS-CoV2 Vims. Post infection, 6 different concentration of test compound were added to infect Vero cells in triplicate at four different time points and these plates were incubated at 37 °C in 5% C02. After incubation, quantitative CPE based scores were made for EC50 determination.
Accordingly, functional food compositions comprising lactoferrin and Jack fruit seed powder were prepared and in vitro antiviral activity of these compositions of Lactoferrin and Jack fruit seed powder of the present invention were compared with the virucidal activity of lactoferrin and Jack fruit seed powder. Assessment of these dmgs in both prophylactic and therapeutic activities were conducted to identify the antiviral potential of the dmg candidate against SARS-CoV-2. The results are shown in below table.
AIPL-SC- 001 is Lactoferrin, AIPL-SC- 012, is Jacalin. In-vitro therapeutic activity of AIPL-001 and AIPL-012 formulations are shown in figure 1 and 2. It is evident from figures 1 lactoferrin is more potent in higher concentrations. However, high therapeutic activity of Jacalin /Jack fruit seed powder exhibits more potent in lower concentrations initially and probably acting on the TMPRSS or Furin (ineffective on MLPro & CL Pro). EC50 of AIPL-012 formulation is 8.5 mM, as shown in figure 3. It is evident from figure 3, SI at 0 Hr = 3.043 / 0.00004 = 76075; SI at 2 or 4 Hr = 3.043 / 8.5 = 0.358 and SI at 1 Hr = 3.043 / 3.9 = 0.78.
The SI values of Lactoferrin, Jacalin and the compositions of examples 1 to 4 are provided in below table.
As is evident from the SI values (Therapeutic mode), the combination of lactoferrin and Jacalin provides synergistic effect, when compared to individual ingredients. The SI values (Therapeutic mode) of all the examples 1 to 4, shows synergy among the constituents of the formulations.
Claims
1. A functional food composition comprising Lactoferrin in an amount of 1 Omg to 4000mg and Jacalin in an amount of 1 Omg to 500mg optionally in association with nutraceutical excipients, for the prevention and treatment of COVID-19.
2. The functional food composition as claimed in claim 1, wherein, the whey protein isolate is present in an amount of lOOg to 4000g and jackfruit seed powder is present in an amount of 250g to 500g along with suitable carrier s/excipients.
3. The functional food composition as claimed in claim 1 , wherein, the lactoferrin is selected from bovine / caprine lactoferrin, colostrum or whey protein isolates containing lactoferrin.
4. The functional food composition as claimed in claim 1, wherein, the nutraceutical excipients/carriers that can be used in the preparation of functional food formulations are selected from the group consisting of controlled release binders, diluents, lubricants, emulsifiers, oily vehicles, colorants, flavoring agents, sweeteners, bioadhesive agents, pH modifiers, controller release polymers, viscosity modifiers, stabilizers, surfactants and cosurfactants, plasticizers, food based carriers, preservatives, and the like.
5. A method for treating or preventing COVID-19 or symptoms associated with COVID-19 in a subject which method comprises administering the subject with a functional food composition comprising lactoferrin in an amount of lOg to 4000g andjackfmit seed powder in an amount of lOg to 500gto alleviate the vims load of SARS CoV-2 / SARS COV from the subject suffering from COVID-19 and to boost the immunity of the subject.
6. The method as claimed in claim 5, wherein, the lactoferrin is selected from Bovine lactoferrin, whey protein isolate and colostmm.
7. Use of a functional food composition comprising combination of Lactoferrin in an amount of lOmg to 4000mg andjackfmit seed powder in an amount of lOmg to 500mg in therapeutically effective amounts optionally in association with nutraceutical excipients, to alleviate the vims load of SARS CoV-2 / SARS COVfrom subject suffering from COVID-19 and to boost the immunity of the subject.
8. The use of a functional food composition as claimed in claim 7, wherein, the lactoferrin is selected from Bovine lactoferrin, colostmm or whey protein isolates containing lactoferrin.
9. The use as claimed in claim 8, wherein the compositions are formulated into a dosage form selected from dry powder form,
liquid form, beverage, food product, dietary supplement or any suitable form such as tablet, a capsule or a soft chewable or gummy bar using a food-based carrier include saccharide or polysaccharide syrups such as sucrose syrup, honey, date syrup, fruit syrups such as maple syrup.
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