Sodium butyrate for use in the prevention or treatment of rhinovirus infections

Abstract

The present invention provides compositions for use in the prevention and / or treatment of infections caused by rhinovirus. [Solution] A composition comprising sodium butyrate for the prevention and / or treatment of viral infections caused by rhinovirus. The composition may further contain vitamin D. The composition may be administered in the form of tablets, capsules, or inhalers. Alternatively, it may be provided as a dietary supplement.

Description

Technical Field

[0001] The present invention relates to a composition for use in preventing and / or treating infections caused by rhinovirus.

Background Art

[0002] Rhinovirus is a major cause of the common cold and is considered to be one of the most common viral infectious agents in humans. There are approximately 160 different serotypes of rhinovirus. Rhinovirus can infect humans with different protein compositions. Acute rhinovirus infection is a viral upper respiratory tract infection.

[0003] Currently, there is no effective vaccine for preventing rhinovirus infection in humans. Typically, children are infected with rhinovirus approximately 8 to 12 times a year, and adults are infected approximately 3 to 4 times a year. The estimated cost of rhinovirus to the US economy is estimated to be approximately $40 billion per year. [[ID=​​​​​​​​​​​​​​​​

[0006] According to a first embodiment, a composition comprising sodium butyrate is provided for use in the prevention, improvement, and / or treatment of viral infections caused by rhinovirus.

[0007] Preferably, a composition comprising sodium butyrate for the prevention and / or treatment of acute rhinovirus infection is provided. Preferably, a composition comprising sodium butyrate for the prevention and / or treatment of viral upper respiratory tract infection is provided. Preferably, the composition comprises sodium butyrate having the formula C4H7NaO2 (or C4H7NaO2).

[0008] Advantageously, the use of the composition containing sodium butyrate results in a reduction and / or elimination of rhinovirus infection within an individual.

[0009] Advantageously, the use of the composition may have a preventive effect against viral infections caused by rhinovirus.

[0010] Typically, the compositions of the present invention act by stimulating an immune response within an individual. Preferably, the compositions stimulate immune cells in an individual to release one or more substances that kill rhinoviruses and / or inhibit rhinovirus replication.

[0011] Advantageously, the use of the composition containing sodium butyrate does not induce antimicrobial resistance in the organism, because the composition acts by stimulating the innate immune response rather than directly targeting the virus itself.

[0012] Advantageously, the compositions of the present invention are easy to manufacture and inexpensive to purchase. Advantageously, when taken within the recommended dosage range, the compositions of the present invention do not cause any side effects in patients.

[0013] In another embodiment, the composition further comprises vitamin D. In one embodiment, the use of a composition comprising sodium butyrate and vitamin D reduces and / or eliminates rhinovirus infection in an individual. Typically, the combination of sodium butyrate and vitamin D stimulates the patient's immune response to reduce and / or eliminate rhinovirus infection in the patient.

[0014] Typically, the composition contains sodium butyrate in an amount between 100 mg and 300 mg. In one embodiment, the composition may contain approximately 2000 mg of sodium butyrate.

[0015] Typically, the composition further comprises vitamin D between 400 IU and 4000 IU (i.e., between 10 μg and 100 μg).

[0016] The aforementioned composition is preferably taken once a day.

[0017] In one embodiment, the composition is provided as a dietary supplement. Advantageously, the provision of the composition as a dietary supplement amplifies the innate immune response of an individual to a virus. Advantageously, supplementation with a dietary supplement using the composition comprising sodium butyrate and / or vitamin D improves the host immune response to rhinovirus.

[0018] Advantageously, sodium butyrate is a naturally occurring substance (short-chain fatty acid) and may be purchased from pharmacies and / or pharmacists, or prescribed to patients as a supplement. Advantageously, sodium butyrate may be taken without a doctor's prescription, within the recommended dosage range, without documented information on side effects.

[0019] In one embodiment, the composition may be administered orally. In a preferred embodiment, the composition may be administered in the form of tablets or capsules. In another embodiment, the composition may be administered in the form of an inhaler, such as a nasal inhaler. Preferably, the composition is taken once a day.

[0020] In one embodiment, the composition may be coated with a material such as a lipid or a sugar, or a combination thereof. Typically, the coating or targeting-inducing material may dissolve to efficiently and sufficiently transport the composition to cells, tissues, or organs.

[0021] In one embodiment, the composition may be incorporated into a food or beverage.

[0022] In one embodiment, the composition may include at least one acceptable carrier. The composition may be carried by vesicles, micelles, liposomes, nanoparticles, or other suitable media.

[0023] According to a second aspect, a dietary supplement comprising the composition according to the first aspect of the present invention is provided.

[0024] According to a third aspect, a tablet comprising the composition according to the first aspect of the present invention is provided.

[0025] According to a fourth aspect, an inhaler comprising the composition according to the first aspect of the present invention is provided.

[0026] In one embodiment, the inhaler is a nasal inhaler.

[0027] According to a fifth aspect, a method for preventing, ameliorating, and / or treating virus infection caused by rhinovirus using the composition comprising sodium butyrate according to the first aspect of the present invention is provided.

[0028] Preferably, a method for preventing, ameliorating, and / or treating acute rhinovirus infection is provided using the composition comprising sodium butyrate according to the first aspect of the present invention.

[0029] In one embodiment, the method comprises the use of a composition comprising sodium butyrate and vitamin D.

[0030] The present invention will be further described by way of example and with reference to the following figures.

Brief Description of the Drawings

[0031] [Figure 1] Figure 1 is a graph showing the effect on rhinovirus-infected cells after treatment with sodium butyrate, vitamin D, or a combination of sodium butyrate and vitamin D.

Mode for Carrying Out the Invention

[0032] Advantageously, the use of the composition comprising sodium butyrate and / or vitamin D results in a reduction and / or elimination of rhinovirus infection in an individual.

[0033] The composition according to the present invention acts through stimulation of the immune response in an individual. Thus, the composition stimulates the immune cells of an individual to release one or more substances that kill / inactivate rhinovirus and / or inhibit the replication of rhinovirus.

[0034] In one embodiment, the composition is provided as a dietary supplement. Advantageously, supplementation with a dietary supplement using sodium butyrate improves the host immune response against rhinovirus. Preferably, the composition is provided in the form of a tablet dietary supplement and is commercially available without a doctor's prescription as a dietary supplement.

[0035] In another embodiment, the composition may be administered in the form of a tablet or capsule. In this embodiment, the composition may be coated with a material such as a lipid or a sugar, or a combination thereof. Typically, the coating or target-inducing material dissolves to efficiently and sufficiently deliver the complex to cells, tissues, or organs.

[0036] Pharmaceuticals, food supplements, or dietary supplements often contain compounds and / or other naturally derived or synthetically synthesized ingredients. These naturally derived or synthetically synthesized ingredients may be active ingredients that provide beneficial effects, or they may be inactive ingredients.

[0037] Inactive ingredients, often referred to as additives, are typically present in pharmaceutical, food, or dietary supplement formulations. The choice of one or more additives in a formulation depends on whether the active ingredient is delivered in tablet, capsule, or liquid form. Alternatively, the choice of additives depends on the manufacturing process.

[0038] The active or inactive component may be a compound that is considered "generally safe" (GRAS) for ingestion by humans or animals.

[0039] Additives may be naturally derived or synthetically produced. Additives have a wide range of physical or chemical properties. The physical or chemical properties depend on the structure of the additive. Properties of additives include, but are not limited to, providing anti-adhesion, binding, bulking, protective or enteric coatings, aiding dissolution or disintegration, providing color, flavor or sweetness, providing fluidity or lubricant effects, solvation, adsorbent or lubricant effects. These properties are beneficial in the formulation, manufacture, or transport of the active ingredient.

[0040] Examples of compositions according to the present invention are described below and contain both active ingredients and additive ingredients that are common in pharmaceuticals and foods or dietary supplements: active ingredient : Vitamin D (CAS No: 69-97-0) 25 micrograms (1000 IU or 25 ug); Sodium butyrate (CAS No: 156-54-7) 300 milligrams (mg); Additives / Inactive Ingredients : Microcrystalline cellulose (CAS No: 9004-34-6) 350 milligrams (mg); Calcium diphosphate (CAS no: 7758-87-4) 300 milligrams (mg); Silica SiO2 (CAS No: 7631-86-9) 20 milligrams (mg); Magnesium stearate (CAS No: 557-04-0) 30 milligrams (mg).

[0041] The formulation in the example above is intended for single, solid oral administration.

[0042] Those skilled in the art will understand the benefits of altering the ratios of the ingredients in the above example formulation to enable the mass production of tablets or capsules for human or animal consumption.

[0043] In another embodiment, the composition may be prepared comprising sodium butyrate as an active ingredient, microcrystalline cellulose as an additive / inactive ingredient in the above amounts, calcium diphosphate, silica SiO2, and magnesium stearate.

[0044] As shown in Figure 1, experiments were conducted to treat leukocytes (human monocytic THP-1 macrophage cell line differentiated into macrophages) with sodium butyrate, vitamin D, or a combination of sodium butyrate and vitamin D.

[0045] The leukocytes were cultured for a period of time to allow them to release proteins into the surrounding cell culture medium (referred to as "conditioned medium"). Then, the conditioned medium was cultured together with HRV1B rhinovirus. The leukocytes were cultured together with a solution containing 0.5 mM sodium butyrate, a solution containing 0.5 mM vitamin D, and a solution containing both 0.5 mM sodium butyrate and 0.5 mM vitamin D.

[0046] The results shown in Figure 1 indicate that culturing with sodium butyrate resulted in a 75–80% reduction in measurable active virus compared to the control (treated with purified water). In addition, culturing with vitamin D alone, or with sodium butyrate and vitamin D, resulted in a significant reduction in measurable active virus compared to the control.

[0047] The data presented above are the average of three independent biological replicate experiments (titration is the average of a 10x reduction quantified over three replicate experiments).

[0048] To provide an effective response to viral infection, sodium butyrate and vitamin D have effects on different intracellular mediators and / or signaling molecules. Therefore, providing a composition containing both sodium butyrate and vitamin D would be advantageous, because some individuals may be more sensitive to either sodium butyrate or vitamin D in the context of innate immunity. Thus, administering a composition containing both sodium butyrate and vitamin D would provide an effective reduction of viral infection in a wider range of people.

[0049] Butyrate has been shown to increase cathelicidine production (Schauber et al, Gut 2003, 52(5), 735-741 and Hase et al, Infect Immun 2002, 70(2), 953-963).

[0050] By reference to the present invention, it is understood that sodium butyrate reduces the level of rhinovirus titer through cathelicidin stimulation.

[0051] In addition, downregulation of inflammation in the context of viral infection may be an additional beneficial outcome, because in rhinovirus infection, a large portion of the symptomatic symptoms can be attributed to virus-induced inflammation (Greenberg, Arch Int Med, 2003 163(3), 278-284). In a mouse model of influenza infection, exogenous LL-37 (a human member of the cathelicidine family) has been shown to reduce inflammation (Barlow et al, PLos One, 2011, 6(10)) and thus improve survival rates. Furthermore, exogenous LL-37 has been shown to reduce the release of rhinovirus-induced inflammatory cytokines in cell models (Casanova et al, Front Immunol 2020, 11 (85)).

[0052] By reference to this invention, it is understood that sodium butyrate may reduce inflammation caused by viral infections through the reduction of nuclear factor κB (NFKappa B) signaling. This would be beneficial for alleviating symptoms of rhinovirus infection.

Claims

1. A composition comprising sodium butyrate for use in the prevention and / or treatment of viral infections caused by rhinovirus.

2. The composition according to claim 1 for use in the prevention and / or treatment of acute rhinovirus infection.

3. The composition according to any one of claims 1 to 2, wherein the composition stimulates immune cells of an individual to release a substance that kills rhinoviruses and / or inhibits rhinovirus replication.

4. The composition according to any one of the claims, further comprising vitamin D.

5. The composition described above is administered orally, as described in any of the claims.

6. The composition according to claim 8, wherein the composition is administered in the form of a tablet or a capsule.

7. The composition according to any one of claims 1 to 4, which is administered in the form of an inhaler.

8. The composition according to any one of claims 1 to 6, wherein the composition is coated with a material such as a lipid or a sugar, or a combination thereof.

9. The composition according to any one of the claims, comprising at least one acceptable carrier which may be carried by vesicles, micelles, liposomes, nanoparticles, or other suitable media.

10. The composition is provided as a dietary supplement, according to any one of the claims.

11. The composition described above is incorporated into a food or beverage, as described in any of the claims.

12. A dietary supplement comprising a composition containing sodium butyrate for the prevention and / or treatment of viral infections caused by rhinovirus.

13. The dietary supplement according to claim 12, further comprising vitamin D.

14. A tablet comprising a composition containing sodium butyrate for the prevention and / or treatment of viral infections caused by rhinovirus.

15. The tablet according to claim 14, further comprising vitamin D.

16. An inhaler comprising a composition containing sodium butyrate for the prevention and / or treatment of viral infections caused by rhinovirus.

17. The inhaler according to claim 16, further comprising vitamin D in the composition.

18. The inhaler according to any one of claims 16 to 17, wherein the inhaler is a nasal inhaler.

19. A method for preventing and / or treating a viral infection caused by rhinovirus, using a composition comprising sodium butyrate according to any one of claims 1 to 11.

20. The method according to claim 19, for preventing and / or treating acute rhinovirus infection using a composition comprising sodium butyrate as described in any one of claims 1 to 11.

21. The method according to any one of claims 19 to 20, comprising the use of a composition comprising sodium butyrate and vitamin D.

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