A composition containing a boswellic acid derivative against SARS-CoV-2

Abstract

A composition comprising a boswellic acid derivative against SARS-CoV-2, wherein the boswellic acid derivative is selected from the group consisting of 3-acetyl-11-keto-β-boswellic acid (AKBA), 11-keto-β-boswellic acid (KBA), β-boswellic acid (β-BA), 3-acetyl-β-boswellic acid (β-ABA), (4β) benzyl 3,11-dioxours-12-en-24-oate, (3α, 4β) benzyl 3-hydroxy-11-oxours-12-en-24-oate, (4β) benzyl 2-bromo-3,11-dioxours-12-en-24-oate, (3α, 4β) benzyl 3-hydroxyurs-12-en-24-oate and (4β) Benzyl 3-oxours-12-en-24-oate, optionally in combination with one or more pharmaceutically acceptable excipients, the composition being formulated for oral administration in the form of tablets, capsules or suspensions.

Description

The present invention relates to the field of pharmaceutical compositions. More particularly, it relates to a composition containing a boswellia acid derivative for the prevention and treatment of viral infections, in particular SARS-CoV-2.SARS-CoV-2, the pathogen of COVID-19, has resulted in a global health crisis due to rapid transfer, high morbidity, and the potential for severe complications. Current therapeutic approaches, including antiviral drugs and supportive treatments, have proven to be only limited in the management of disease processes, particularly in the control of inflammatory responses and cytokine towers associated with severe cases. Moreover, new viral variants complicate treatment results, which illustrates the urgent need for alternative therapeutic strategies that are both effective and safe.Boswellia acids, bioactive compounds from Boswellia species resin, are known for their potent anti-inflammatory, immunomodulatory and antiviral properties. Despite their therapeutic potential, conventional boswellic acid compounds have poor bioavailability and limited efficacy in systemic infections. Recent advances in the modification of boswellic acid derivatives have shown improved pharmacokinetic profiles, increased biological activity and targeted therapeutic advantages, making them promising candidates for the treatment of viral infections, including SARS-CoV-2.The present invention provides a novel composition containing an optimized boswellic acid derivative specifically formulated for inhibiting SARS-CoV-2 replication, modulating inflammatory responses, and reducing cytokine mediated complications. By overcoming the limits of existing treatments and exploiting the improved properties of boswellic acid derivatives, this invention provides an effective, targeted therapeutic approach for the prevention and treatment of COVID-19 and related viral infections.An object of the present disclosure is that the composition offers a vegetable, natural therapeutic option for treating SARS-CoV-2 infections.It is a further object of the present disclosure that the boswellia acid derivatives have a strong binding affinity to the SARS-CoV-2 spike protein receptor binding domain.Another object of the present disclosure is that the composition ensures rapid disintegration and dissolution, which allows rapid onset of action.Another object of the present disclosure is that the tablets have excellent stability under accelerated storage conditions, which ensures longer shelf life.It is a further object of the present disclosure that the composition has increased antiviral activity by inhibiting viral entry into the host cells.Another object of the present disclosure is that the manufacturing process is simple, scalable, and inexpensive for large scale production.Another object of the present disclosure is that the composition has the potential for lower side effects due to its natural origin and targeting mechanism.Another object of the present disclosure is that the invention can be administered orally, which is convenient for the patient and enables better compliance.The present invention relates generally to a pharmaceutical composition containing boswellia acid derivatives for treating SARS-CoV-2 infections.Structurally modified boswellia acid molecules with enhanced antiviral activity are used.One embodiment of the present invention is that the key derivatives (3α,4β) comprise benzyl 3-hydroxyurs-12-ene-24-oat (C2) and related analogs synthesized from β-boswellic acid.Another embodiment of the invention is that molecular docking studies have yielded excellent interactions such as hydrogen bonds, π-π stacking, and ionic interactions.Another embodiment of the invention is that the pharmaceutical composition is formulated in the form of a solid oral dosage form, such as tablets or capsules.The composition provides optimum bioavailability and rapid release of the active ingredient for effective therapeutic effect.A further embodiment of the invention consists in that the tablet formulation contains pharmaceutically acceptable excipients such as microcrystalline cellulose, povidone K30 and magnesium stearate.Another embodiment of the invention is that in vitro dissolution studies confirm release of greater than 85% of the boswellic acid derivative within 30 minutes.Another embodiment of the invention demonstrates stability under accelerated storage conditions while maintaining drug efficacy and performance.EXAMPLE 1: Preparation:The preparation of the boswellia acid derivatives used in the present invention includes both isolation from natural sources and chemical synthesis according to established protocols. First, important precursor compounds such as 3-acetyl-11-keto-β-boswellic acid (AKBA, C1), β-boswellic acid (β-BA, C4), 3-acetyl-β-boswellic acid (β-ABA, C5), and 11-keto-β-boswellic acid (KBA, C6) were isolated from the resin of Boswellia sacra by conventional chromatographic techniques including solvent extraction followed by column chromatography and recrystallization as described in the literature

[30] .Following isolation, synthetic modifications were made to improve the antiviral activity and pharmacokinetic properties of these compounds. Thus, for example, compound C6 (KBA) served as starting material for the synthesis of three novel derivatives: (4β) benzyl 3,11-dioxours-12-ene-24-oate (C7), (3α, 4β) benzyl 3-hydroxy-11-oxours-12-ene-24-oate (C9) and (4β) benzyl 2-bromo-3,11-dioxours-12-ene-24-oate (C8). These compounds were synthesized by benzylating the C-24 carboxyl group and functional modifications at the C-3 and C-11 positions using standard esterification, hydroxylation and halogenation reactions as described in the protocolsSimilarly, two other derivatives, (3α,4β) benzyl 3-hydroxyurs-12-ene-24-oate (C2) and (4β) benzyl 3-oxours-12-ene-24-oate (C3), were synthesized from compound C4 (β-BA). These synthesis steps involved the selective benzylation of the C-24carboxylic acid group and the oxidation / reduction at the C-3 position to introduce hydroxyl or keto groups according to the established methods. The final products were purified by chromatographic methods and characterized by spectroscopic methods such as NMR and mass spectrometry to confirm their structures and purity.EXAMPLE 3: A composition for the treatment of SARS-CoV-2 infectionsThe present invention relates to a pharmaceutical composition containing one or more boswellia acid derivatives as active ingredient and formulated for the prevention and treatment of SARS-CoV-2 infection. The composition contains pharmaceutically acceptable excipients and is suitable for oral, injectable or inhaling administration.One or more boswellic acid derivatives selected from the group consisting of:◯ 3-acetyl-11-keto-β-boswellic acid (AKBA, C1)◯ β-Boswellic acid (β-BA, C4)◯ 3-acetyl-β-boswellic acid (β-ABA, C5)◯ 11-Keto-β-boswellic acid (KBA, C6)◯ (4β) Benzyl 3,11-dioxours-12-ene-24-oate (C7)◯ (3α,4β) Benzyl 3-hydroxy-11-oxours-12-ene-24-oate (C9)◯ (4β) Benzyl 2-bromo-3,11-dioxours-12-ene-24-oate (C8)◯ (3α,4β) Benzyl 3-hydroxyurs-12-ene-24-oate (C2)◯ (4β) Benzyl 3-oxours-12-ene-24-oate (C3)Ingredient Amount per tablet (mg)Active Ingredient 100Microcrystalline cellulose 150Povidone (binder) 20Croscarmellose sodium (disintegrant) 15Magnesium stearate (lubricant) 5EXAMPLE 4: PreparationThe oral tablet containing the boswellic acid derivatives is prepared by accurately weighing and sieving the active ingredient together with microcrystalline cellulose through a 40 mesh sieve and then mixing in a blender for uniform distribution. A binder solution is prepared by dissolving povidone K30 in purified water or isopropyl alcohol and added gradually to the mixture to form a wet mass which is then passed through a 16 mesh screen for wet granulation. The granulate is dried in a tray dryer at 50°C-60°C until the optimum moisture content is reached and subsequently sieved through a 20 mesh sieve for uniform granulation. Extragranular excipients such as croscarmellose sodium (disintegrant) and magnesium stearate (glidant) are added and mixed gently. The final blend is compressed into tablets using a rotary compression machine which can then be film coated if desired. The tablets are then subjected to standard quality control to ensure consistency, effectiveness and performance.EXAMPLE 5: EvaluationsExternal appearanceThe appearance of the Boswellia acid derivative tablets was visually examined under appropriate white light. The tablets were tested for uniform color, shape and surface finish, ensuring that no physical defects such as cracks, stains or chipping were present. A consistent appearance is important because it reflects proper formulation and manufacturing practice. The tablets had a smooth surface with uniform coloration, confirming their physical integrity.Weight variationsThe weight fluctuations were determined by individually weighing twenty randomly selected tablets with a calibrated analytical balance. Individual weights were compared to the average tablet weight to ensure uniformity of dosage. The permissible limit for weight fluctuations for tablets above 250 mg is 5%. All tablets were within the indicated range, confirming consistency and accuracy of tablet compression during manufacture.Hardness (breaking strength)The tablet hardness was evaluated with a Monsanto hardness tester to measure the force required to break the tablets. Ten tablets were tested and the results were given in kg / cm 2. Adequate hardness ensures mechanical strength and prevents breakage during handling and packaging. The tablets had a hardness range of 5 to 8 kg / cm 2 ensuring that they are durable without being too hard to disintegrate.FriabilityThe friability test was carried out with a Roche Friabilator, in which ten weighed tablets were rotated at 25 U / min for 4 minutes. After the test, the tablets were dusted and reweighed to calculate the weight loss percentage. Tablets with friability below 1% are considered abrasion resistant. The results showed a weight loss of less than 1%, confirming that the tablets can withstand the mechanical loads during packaging and transport.Dissolution timeThe disintegration test was performed on six tablets using the USP disintegration test with distilled water at 37 ± 0.5°C. The time required for complete disintegration was recorded. According to the Pharmacopoeia standards, the uncoated tablets should dissolve within 15 minutes. All tablets passed the test and disintegrated within the indicated time, so that a rapid release of active ingredient was ensured after oral administration.Test (Uniformity of Drug Content)The uniformity of the drug content was determined by HPLC analysis of the comminuted and methanol dissolved tablets. Samples were filtered and injected into the 254 nm detection HPLC system using a C18 column. The results confirmed that each tablet contained between 98% and 102 % of the marked dose of the boswellic acid derivative. This ensures that the correct dose is administered with each tablet and the therapeutic efficacy is retained.Dissolution studyIn vitro dissolution was performed with a USP type II apparatus (paddles) in 900 ml phosphate buffer (pH 6.8) at 37 ± 0.5°C and a paddle speed of 50 U / min. Samples were taken at regular intervals and analyzed by UV spectrophotometry at 254 nm. The study showed that more than 85% of the drug was released within 30 minutes, confirming rapid and efficient dissolution of the drug for therapeutic effect.Stability StudyAccelerated stability studies were performed by storing the tablets at 40±2° C. and 75±5% atmospheric humidity for three months. The samples were examined periodically for appearance, drug content and dissolution behavior. No significant changes were detected in any of the parameters. The results indicated that the tablets were stable under accelerated conditions and provided adequate durability and product quality over a prolonged period of time.Examples1. A composition comprising a boswellic acid derivative against SARS-CoV-2, wherein the boswellic acid derivative is selected from the group consisting of 3-acetyl-11-keto-β-boswellic acid (AKBA), 11-keto-β-boswellic acid (KBA), β-boswellic acid (β-BA), 3-acetyl-β-boswellic acid (β-ABA), (4β) benzyl 3,11-dioxours-12-ene-24-oat, (3α, 4β) benzyl 3-hydroxy-11-oxours-12-ene-24-oat, (4β) benzyl 2-bromo-3,11-dioxours-12-ene-24-oat, (3α,4β) Benzyl 3-hydroxyurs-12-ene-24-oat and (4β) Benzyl 3-oxours-12-ene-24-oat, optionally in combination with one or more pharmaceutically acceptable excipients, wherein the composition is formulated for oral administration in the form of tablets, capsules or suspensions.

Claims

A composition comprising a boswellic acid derivative against SARS-CoV-2, wherein the boswellic acid derivative is selected from the group consisting of 3-acetyl-11-keto-β-boswellic acid (AKBA), 11-keto-β-boswellic acid (KBA), β-boswellic acid (β-BA), 3-acetyl-β-boswellic acid (β-ABA), (4β) benzyl 3,11-dioxours-12-ene-24-oat, (3α, 4β) benzyl 3-hydroxy-11-oxours-12-ene-24-oat, (4β) benzyl 2-bromo-3,11-dioxours-12-ene-24-oat, (3α,4β) Benzyl 3-hydroxyurs-12-ene-24-oat and (4β) Benzyl 3-oxours-12-ene-24-oat, optionally in combination with one or more pharmaceutically acceptable excipients, wherein the composition is formulated for oral administration in the form of tablets, capsules or suspensions.The composition of claim 1, wherein the boswellia acid derivative is 3α,4β-benzyl-3-hydroxyurs-12-ene-24-oate in an amount of 50 mg to 200 mg per unit dosage.The composition of claim 1 or 2, wherein the pharmaceutically acceptable excipients comprise diluents, binders, disintegrants, lubricants and lubricants.The composition of any preceding claim, wherein the diluent is microcrystalline cellulose or lactose monohydrate in an amount of 20-40% (w / w) of the total composition.Composition according to any one of the preceding claims, wherein the binder is selected from polyvinylpyrrolidone (PVP K30) or pregelatinized starch in an amount of 2-5% w / w.A composition according to any preceding claim wherein the disintegrant is croscarmellose sodium or sodium starch glycolate in an amount of from 2 to 4% by weight.The composition of any preceding claim, wherein the lubricant is magnesium stearate in an amount of 0.5-1% (w / w) of the total composition.A composition according to any preceding claim, wherein the composition has a disintegration time of less than 15 minutes and releases not less than 85% of the boswellia acid derivative within 30 minutes in a phosphate buffer solution having a pH of 6.8 at 37 ± 0.5°C.