US008551.496 B2

(12) United States Patent (10) Patent No.: US 8,551.496 B2 Gokaraju et al. (45) Date of Patent: Oct. 8, 2013

(54) BOSWELLIA LOW POLAR GUM RESIN OTHER PUBLICATIONS EXTRACT AND ITS SYNERGISTC COMPOSITIONS Kasali et al. (2002) Flavour Fragr. J. 17:462-464.* Krohnet al. (2001) Phytochem. Anal. 12:374-376.* (75) Inventors: Ganga Raju Gokaraju, Vijayawada Mahajan et al. (1995) Phytochemistry, vol.39, No. 2, pp. 453-455.* Ammon (2006) Planta Medical Natural Products and Medicinal (IN); Rama Raju Gokaraju, Plant Research 72.12 (2006): 1100-11 16.* Vijayawada (IN); Ventaka Kanaka Chevrier et al. (2005) Clin. Diagn. Lab. Immunol. 12(5): 575-580.* Ranga Raju Gokaraju, Vijayawada Houssen et al. (2010) Clinical Biochemistry 43: 887-890.* (IN); Trimurtulu Golakoti, Vijayawada Baser, S. Chemical Investigations on Boswellia Species, University (IN); Kiran Bhupathiraju, Vijayawada of Hamburg (online), Mar. 18, 2005, pp. 1-256, retrieved from the (IN) Internet: (http://www.boswellness.com/sites/default/files/pdfs/Dis SertationBasar.pdf) on Aug. 10, 2012. (73) Assignee: Laila Nutraceuticals, Vijayawada (IN) Al-Harrasi et al., Phytochemical Analysis of the Essential Oil from Botanically Certified Oleogum Resin of Boswellia sacra (Omani (*) Notice: Subject to any disclaimer, the term of this Luban), Molecules. Sep. 16, 2008. vol. 13, No. 9, pp. 218 1-2 189. patent is extended or adjusted under 35 Ehrman et al., Phytochemical Databases of Chinese Herbal Constitu U.S.C. 154(b) by 0 days. ents and Bioactive Plant Compounds with Known Target Specifici ties. Journal of Chemical Information and Modelling, Jan. 9, 2007. (21) Appl. No.: 13/584,099 vol. 47, No. 2, pp. 254-263. Cuaz-Perolin et al., Antiinflammatory and Antiatherogenic Effects of (22) Filed: Aug. 13, 2012 the NF-kB Inhibitor Acetyl-11-Keto-B-Boswellic Acid in LPS-Chal lenged ApoE / Mice, Arterioscler Thromb Vasc Biol. 2008; (65) Prior Publication Data 28:272-277. Kimmatkar et al., Efficacy and tolerability of Boswellia serrata US 2012/O3O1432 A1 Nov. 29, 2012 extract in treatment of osteoarthritis of knee-A randomized double blind placebo controlled trial. Phytomedicine 10: 3-7 (2003). Related U.S. Application Data Ernst, Frankincense:systematic review, BMJ 2008; 337:a2813. (63) Continuation-in-part of application No. Safayhi et al., Inhibition by Boswellic Acids of Huma Leukocyte PCT/IN2010/000233, filed on Apr. 12, 2010. Elastase, Journal of Pharmacology and Experimental Therapeutics 281:460-463. 1997. (30) Foreign Application Priority Data Sailer et al., Acetyl-11-keto-B-boswellic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity. Feb. 15, 2010 (IN) ...... 384f CHEA2010 British Journal of Pharmacology. (1996) 117,615-618. International Search Report dated for PCT/IN2010/000233 dated (51) Int. Cl. Oct. 5, 2010. A6 IK3I/00 (2006.01) A6 IK35/00 (2006.01) * cited by examiner A6 IK36/00 (2006.01) A6 IK36/906 (2006.01) Primary Examiner — Chris R Tate (52) U.S. Cl. Assistant Examiner — Russell Fiebig USPC ...... 424/195.18; 424/725; 424/756 (74) Attorney, Agent, or Firm — Kramer Amado, P.C. (58) Field of Classification Search None (57) ABSTRACT See application file for complete search history. The present disclosure describes Boswellia low polar gum resin extract (BLPRE) comprising novel phytochemical com (56) References Cited position of sesquiterpenes, diterpenes, triterpenes and other phytochemical(s) obtained from gum resin of Boswellia spe U.S. PATENT DOCUMENTS cies. The present disclosure also describes compositions 5,629.351 A * 5/1997 Taneja et al...... 514,765

comprising BLPRE in combination with one or more com 6,589,516 B1* 7/2003 Eyre et al...... 424.70.1 2004/0202709 A1 10/2004 Kirby et al. ponent(s) selected from biologically active ingredient(s), 2005/0282772 A1* 12/2005 Gokaraju et al...... 514/54 functional ingredient(s), excipient(s), diluents(s), carrier(s) 2006,0040000 A1 2/2006 Gokaraju et al. and additive(s) or mixtures thereof. Further the present dis 2006, OO62859 A1 3, 2006 Blum et al. closure also provides synergistic composition(s) comprising 2006/0280811 A1 12/2006 Bombardelli 2007/0281045 A1 12/2007 Tripp et al. Boswellia low polar gum resin extract (BLPRE) and at least 2008/0275117 A1 11, 2008 Li et al. one component selected from but not limited to extract(s), 2008/0317885 A1 12, 2008 Baker fraction(s), phytochemical(s) or their salts or mixtures thereof derived from Boswellia species or Curcuma species. FOREIGN PATENT DOCUMENTS WO O215916 2, 2002 28 Claims, 4 Drawing Sheets U.S. Patent Oct. 8, 2013 Sheet 1 of 4 US 8,551.496 B2

FIG. 1

Oh 2 R = OH and R = H 3 R = H and R = OH

s

4. 2.

U.S. Patent Oct. 8, 2013 Sheet 2 of 4 US 8.551.496 B2

FIG. 2

600 2.00 4.00. 6.00 800 1000 12.00 400 16.00 1800 2000 2200 24.00 2600 2800 3000 3200 34.00 36.00 38.00 4000 42.00 Minutes

A: chromatogram at 252 mm

0.0. M

0. e 0.0

uxL S s n w 0.05 r se st ce - o s co s A /\ 0.00 W AA A Sya

-0.05 20 4.00 so 8.00 10.00 1200 1400 1so 18.0 2000 2200 24.00 26.00 2ao 30.00 o 3400 38.00 38.00 40.00 Minutes

B: chromatogram at 210 nm U.S. Patent Oct. 8, 2013 Sheet 3 of 4 US 8,551.496 B2

FIG 3

5-LOX inhibition at 10 g/ml

BSLPRE BCLPRE BSE 85% BCE 85% BSE 55% Composition-3A Composition-4 Composition-18 Composition-7A U.S. Patent Oct. 8, 2013 Sheet 4 of 4 US 8,551.496 B2

FIG. 4

% reduct ion in paw e dema

% reduction in paw edema

US 8,551.496 B2 1. 2 BOSWELLIA LOW POLAR GUMI RESN (AKBA) is biologically the most active component among its EXTRACT AND ITS SYNERGISTC congeners, with an ICs of 1.5 uM for the inhibition of COMPOSITIONS 5-LOX. There is, however, no known prior art relating to Boswellia CROSS-REFERENCE TO APPLICATIONS 5 low polar gum resin extract (BLPRE) comprising a phy tochemical composition of Sesquiterpenes, diterpenes, and This application is a continuation-in-part of international triterpenes or compositions thereof, for the prevention, con application PCT/IN2010/000233, published as WO 2011/ trol and treatment of disorders or diseases in warm blooded 099029, filed on Apr. 12, 2010. The entire disclosures of animals. international application PCT/IN2010/000233 is hereby 10 incorporated by reference in their entirety. SUMMARY FIELD OF THE DISCLOSURE In an important aspect, the present disclosure provides a Boswellia low polar gum resin extract (BLPRE) comprising The present disclosure provides Boswellia low polar gum 15 novel phytochemical composition of sesquiterpenes, diterpe resin extract (BLPRE) comprising novel phytochemical com nes, triterpenes and other phytochemical(s) obtained from the position(s) of sesquiterpenes, diterpenes, triterpenes and gum resin of Boswellia species. other phytochemical(s) obtained from gum resin of Boswellia Another aspect of the disclosure is to provide composi species. tion(s) comprising Boswellia low polar gum resin extract The disclosure also provides compositions comprising (BLPRE) in combination with at least one component Boswellia low polar gum resin extract (BLPRE) and at least selected from biologically active ingredient(s), functional one component selected from biologically active ingre ingredient(s), excipient(s), diluents(s), carrier(s) and additi dient(s), functional ingredient(s), excipient(s), diluents(s). ve(s) or mixtures thereof. carrier(s) and additive(s) or mixtures thereof. Another major aspect of the present disclosure is to provide Further the disclosure also provides Synergistic composi 25 synergistic composition(s) comprising Boswellia low polar tion(s) comprising Boswellia low polar gum resin extract gum resin extract (BLPRE) in combination with at least one (BLPRE) and at least one component selected from ex component selected from polar extracts orphytochemicals, or tract(s), fraction(s), phytochemical(s) and their salts or mix their salts or mixtures, where the polar extracts or phy tures thereof derived from Boswellia species or Curcuma tochemicals are derived from Boswellia species. species. 30 Another aspect of the present disclosure is to provide Syn ergistic composition(s) comprising Boswellia low polar gum BACKGROUND resin extract (BLPRE) and at least one component selected from the extract(s), fraction(s), phytochemical(s) and their There are numerous pharmaceutical, herbal ingredient(s) salts or mixtures thereof derived from Curcuma species. and biologically active molecules that are effective invitro for 35 Another aspect of the disclosure is to provide synergistic a disease or disorder. However, several of them are not effec composition(s) of Boswellia low polar gum resin extract (BL tive or not bioavailable in vivo (warm blooded animals). It is PRE) with at least one component selected from but not thus important to explore, identify and invent safe and effec limited to biologically active ingredient(s), functional ingre tive compound(s) or composition(s) that helps increase the in dient(s) or mixtures thereof. Vivo activity of Such pharmaceutical or herbal ingredient(s) 40 Another aspect of the disclosure is to provide Boswellia through synergism. In this process the inventors have low polar gum resin extract (BLPRE) comprising a novel screened a number of extracts, fractions, phytochemical(s) phytochemical composition and its compositions for use in and compound(s) originating from plants, animals and micro warm blooded animal(s) in need thereof. organisms; individually and in combinations. Various embodiments disclosed herein relate to a The gum resin of Boswellia has been very widely used 45 Boswellia low polar gum resin extract (BLPRE) comprising a since ancient times. For example, the gum resin of Boswellia phytochemical composition of sesquiterpenes, diterpenes, serrata (Burseraceae) plant has long been in use for the treat triterpenes, and other phytochemicals derived from a gum ment of rheumatoid arthritis and gout by the practitioners of resin of at least one plant in the genus Boswellia. The BLPRE Ayurvedic medicines in the Indian system of medicine. Vari is obtained after selectively removing acidic and volatile ous extracts of the gum resin have shown potent anti-inflam 50 compounds from the gum resin. In various embodiments, the matory and anti-atherogenic activity in laboratory. The Boswellia low polar gum resin extract (BLPRE) is derived extract of Boswellia was found to be a potent anti-arthritic. from a plant selected from the group consisting of Boswellia Boswellia gum resin and its extracts also demonstrated Sig serrata, Boswellia carterii, Boswellia papyrifera, Boswellia nificant therapeutic improvements in human clinical trials ameero, Boswellia bullata, Boswellia dalzielii, Boswellia confirming the in vivo anti-inflammatory effects. 55 dioscorides, Boswellia elongata, Boswellia frereana, The origin of the anti-inflammatory action of Boswellia Boswellia nana, Boswellia neglecta, Boswellia Ogadensis, gum resin and its extracts has been attributed to a group of Boswellia pirottae, Boswellia popoviana, Boswellia rivae, triterpene acids called Boswellic acids that were isolated Boswellia sacra and Boswellia Socotrana, and mixtures from the gum resin of Boswellia serrata. Boswellic acids thereof. In certain embodiments, the plant in the genus exertanti-inflammatory actions by inhibiting 5-lipoxygenase 60 Boswellia is selected from the group consisting of Boswellia (5-LOX). 5-LOX is a key enzyme for the biosynthesis of serrata, Boswellia Carterii, Boswellia papyrifera, and mix leukotrienes from arachidonic acid. Leukotrienes are consid tures thereof. ered to be involved in the initiation and propagation of a According to certain embodiments, the BLPRE is derived variety of inflammatory diseases. In addition to their 5-li from Boswellia serrata gum resin, and comprises at least poxygenase inhibition, Boswellic acids inhibit human leuko 65 three compounds selected from guiol (1), nephthenol (2), cyte elastase (HLE), an enzyme of different pro-inflamma serratol (3), diterpene X (4), lupeol (5), olean-12-ene-3?-ol tory pathway. 3-O-Acetyl-11-keto-B-Boswellic acid (6), olean-12-ene-3C-ol (7), lanosta-8.24-diene-3C-ol (8) and US 8,551.496 B2 3 4 urs-12-ene-3C.-ol (9), as shown in FIG. 1. The BLPRE is Boswellia bullata, Boswellia dalzieli, Boswellia dioScorides, derived from Boswellia serrata gum resin after selectively Boswellia elongata, Boswellia frereana, Boswellia nana, removing acidic and Volatile compounds from the gum resin. Boswellia neglecta, Boswellia Ogadensis, Boswelliapirottae, Various embodiments of processes for preparation of a Boswellia popoviana, Boswellia rivae, Boswellia sacra and composition comprising the BLPRE include the steps of: Boswellia Socotrana, and mixtures thereof. In some embodi a) procuring gum resin of at least one plant of the genus ments of these processes, the term “gum resin of at least one Boswellia, plant of the genus Boswellia” may refer to gum resin of at b) preparing an extract solution of the gum resin with a least one plant selected from the group consisting of water immiscible organic solvent; Boswellia serrata, Boswellia carterii, Boswellia papyrifera, c) evaporating the water immiscible organic solvent from 10 and mixtures thereof. the extract Solution to obtain an oily residue, and d) removing Volatile compounds from the oily residue According to various processes disclosed herein, a syner under high vacuum and high temperature to obtain the gistic composition may be prepared by obtaining a boswellic BLPRE. acid-containing extract of at least one plant selected from the Some processes for preparation of a composition compris 15 group consisting of Boswellia serrata, Boswellia Carterii, ing the BLPRE include the steps of: Boswellia papyrifera, and mixtures thereof combining the a) procuring gum resin of at least one plant of the genus BLPRE and the boswellic acid-containing extract in a desired Boswellia, ratio to obtain the Synergistic composition; and optionally b) extracting the gum resin with a water immiscible organic combining the synergistic composition with at least one com Solvent, Such as 1,2-dichloroethane, hexane, dichlo ponent selected from the group consisting of biologically romethane, chloroform, ethyl acetate, n-butanol, methyl active ingredients, excipients, diluents, carriers and additives. iso-butyl ketone (MIBK), or mixtures thereof, to pro According to other processes disclosed herein, a synergis duce a solution of an organic solvent extract; tic composition may be prepared by obtaining a curcuminoid c) washing the organic solvent extract solution at least once containing extract of at least one plant from the genus Cur with an aqueous solution of a metal hydroxide salt; 25 cuma; combining the BLPRE and the curcuminoid d) Subsequent to step (c), washing the organic solvent containing extract in a desired ratio to obtain the Synergistic extract solution with water, brine, or a mixture thereof composition; and optionally combining the synergistic com e) evaporating the water immiscible organic solvent from position with at least one component selected from the group the organic solvent extract solution to obtain an oily consisting of biologically active ingredients, excipients, dilu residue; and 30 ents, carriers and additives. f) removing Volatile compounds from the oily residue Various embodiments disclosed herein relate to composi under high vacuum and high temperature to obtain the tions comprising the BLPRE and at least one biologically BLPRE. active component selected from the group consisting of at Other processes for preparation of a composition compris least one boswellic acid or a salt thereof a boswellic acid ing the BLPRE include the steps of: 35 containing extract of at least one plant selected from the group a) procuring gum resin of at least one plant of the genus consisting of Boswellia serrata, Boswellia carterii, Boswellia Boswellia, papyrifera, and mixtures thereof, at least one curcuminoid or b) extracting the gum resin with an alcoholic Solvent or a a salt thereof, and a curcuminoid-containing extract of a plant hydroalcoholic solvent to produce an alcoholic extract from the genus Curcuna. If the biologically active ingredient Solution; 40 is a boswellic acid-containing extract, the boswellic acid c) evaporating at least a portion of the alcoholic solvent or containing extract may comprise between about 30% and the hydroalcoholic solvent to produce a concentrated about 100% total boswellic acids. If the biologically active Solution; ingredient is a curcuminoid-containing extract, the curcumi d) adjusting the pH of the concentrated solution to between noid-containing extract may comprise between about 20% about 9 and about 12; and 45 and 99% of said at least one curcuminoid. The curcuminoid e) extracting the concentrated Solution with the water containing extract may be an extract of a plant selected from immiscible organic solvent to produce an extract solu the group consisting of Curcuma longa, Curcuma aromatic, tion comprising the water immiscible organic solvent; and mixtures thereof. f) evaporating said water immiscible solvent from the In various embodiments, the compositions comprise from extract Solution to obtain an oily residue, and 50 about 5% to about 95%, preferably from about 20% to about g) removing Volatile compounds from the oily residue 80%, more preferably from about 33% to about 67%, by under high vacuum and high temperature to obtain the weight of the boswellic acid-containing extract, and from BLPRE. about 5% to about 95%, preferably from about 20% to about In certain embodiments, the step of evaporating at least a 80%, more preferably from about 33% to about 67%, by portion of the alcoholic solvent or the hydroalcoholic solvent 55 weight of said BLPRE. comprises evaporating at least 20%, preferably at least 40%, In other embodiments, the compositions comprise from more preferably at least 60% of the alcoholic or hydroalco about 5% to about 95%, preferably from about 20% to about holic solvent. In various embodiments, the solvent is a 80%, more preferably from about 33% to about 67%, by hydroalcoholic solvent, and the step of evaporating at least a weight of the curcuminoid-containing extract, and from about portion of the solvent comprises evaporating at least 50%, 60 5% to about 95%, preferably from about 20% to about 80%, preferably at least 75%, more preferably substantially all of more preferably from about 33% to about 67%, by weight of the alcohol in the hydroalcoholic solvent. Said BLPRE. In various embodiments of the processes described above, In additional embodiments, the compositions may addi the term "gum resin of at least one plant of the genus tionally comprise at least one component derived from a Boswellia may refer to gum resin of at least one plant 65 plant, an animal, a microorganism, or a mixture thereof. The selected from the group consisting of Boswellia serrata, compositions may also comprise one or more ingredients Boswellia carterii, Boswellia papyrifera, Boswellia ameero, selected from the group consisting of herbal ingredients, anti US 8,551.496 B2 5 6 oxidants, vitamins, minerals, amino acids, fatty acids, essen lic acids (BSE 65%, 200 mg/kg BW), Curcuma longa extract tial oils, fish oils, enzymes and probiotics. standardized to 20% total curcuminoids (CLE 20%, 200 Various embodiments disclosed herein relate to methods of mg/kg BW), Curcuma longa extract standardized to 95% treating inflammation in a warm blooded animal, by admin total curcuminoids (CLE 95%, 200 mg/kg BW), Curcuma istering the BLPRE to said warm blooded animal. In various aromatica extract standardized to 20% total curcuminoids embodiments, the BLPRE may be administered alone or in (CAE 20%, 200 mg/kg BW), Curcuma aromatica extract combination with a boswellic acid-containing extract, a cur standardized to 95% total curcuminoids (CAE 95%, 200 cuminoid-containing extract, or a mixture thereof. mg/kg BW), composition-3A (200 mg/kg BW), composi Various embodiments disclosed herein relate to methods of tion-4 (200 mg/kg BW), composition-18 (200 mg/kg BW), treating a condition associated with at least one biological 10 composition-7A (200 mg/kg BW), composition-42 (200 marker in a warm blooded animal, by administering the mg/kg BW), composition-26 (200 mg/kg BW), composition BLPRE to said warm blooded animal, said biological marker being selected from the group consisting of 5-lipoxygenase 51 (200 mg/kg BW), composition-35 (200 mg/kg BW) and (5-LOX), 5-Lipoxygenase activating protein (FLAP), Mac Prednisolone (10 mg/kg BW). 15 rophage/Adipocyte Fatty acid binding protein (aP2), IFN-y, DETAILED DESCRIPTION IL-4, ICAM, VCAM, MMPs, TNFC, NFKB, IL-1B, and com binations thereof. Again, the BLPRE may be administered alone or in combination with the boswellic acid-containing Abbreviations and words used in the description: extract, the curcuminoid-containing extract, or a mixture 1. BLPRE (Boswellia low polar gum resin extract obtained thereof. from Boswellia species) Another aspect of the present disclosure is to provide 2. BSLPRE (Boswellia serrata low polar gum resin extract Boswellia low polar gum resin extract (BLPRE) comprising a obtained from Boswellia serrata) novel phytochemical composition alone and its compositions 3.BcLPRE (Boswellia carterii low polar gum resin extract for the prevention, control and treatment of one or more obtained from Boswellia carterii) disorder(s) or disease(s) in warm blooded animals, including 25 4. BSE 85% (Boswellia serrata extract standardized to but not limited to metabolic disorders, diabetes, obesity, 85% Boswellic acids) metabolic syndrome, excess body weight, inflammation, 5. BCE 85% (Boswellia carterii extract standardized to asthma, Alzheimer's, cognitive disorders, neurological disor 85% Boswellic acids) ders, cartilage degradation, aging, skin disorders, hyper trig 6. BSE 65% (Boswellia serrata extract standardized to lyceridemia, hyperlipidemia, hypercholesterolemia, choles 30 65% Boswellic acids) terol disorders, hypertension, high blood pressure, immune 7. BCE 65% (Boswellia carterii extract standardized to disorders, cancer, coronary heart disease, infectious diseases, 65% Boswellic acids) osteoporosis, osteoarthritis, rheumatoid arthritis, joint pain, 8. CLE 20% (Curcuma longa extract standardized to 20% joint discomfort and several other conditions associated Curcuminoids) thereof. 35 9. CLE 95% (Curcuma longa extract standardized to 95% BRIEF DESCRIPTION OF FIGURES Curcuminoids) 10. CAE 20% (Curcuma aromatica extract standardized to FIG. 1: Figure shows structural formulae 1-9 representing 20% Curcuminoids) prominent compounds of Boswellia low polar gum resin 40 11. CAE 95% (Curcuma aromatica extract standardized to extract (BLPRE). 95% Curcuminoids) FIG. 2: Figure shows the HPLC chromatogram depicting 12. The terms Gum' or Gum resin or resin used in this the phytochemical profile of Boswellia low polar gum resin patent application are meant to be used interchangeably extract (BLPRE). and they all refer to an exudate of Boswellia plant spe FIG. 3: Figure shows comparative 5-Lipoxygenase inhibi 45 cies. tory activity of Boswellia serrata low polar gum resin extract 13. The word composition wherever used in the patent (BSLPRE), Boswellia carterii low polar gum resin extract application either refers to the novel Boswellia low polar (BcLPRE), Boswellia serrata extract standardized to 85% resin extract (BLPRE) as a standalone ingredient or a total Boswellic acids BSE 85%, Boswellia carterii extract mixture comprising BLPRE in combination with one or standardized to 85% total Boswellic acids BCE 85%. 50 more ingredients such as biologically active ingre Boswellia Serrata extract standardized to 65% total Boswell dient(s), functional ingredient(s), excipient(s), dilu lic acids BSE 65%, composition-3A, composition-4, com ents(s), carrier(s) and additive(s) for preparing either position-18 and composition-7A. The bars represent percent general composition(s) or synergistic composition(s). age inhibition of 5-Lipoxygenase enzyme exhibited by 14. Boswellia low polar resin extract or low polar resin BsLPRE, BcLPRE, BSE 85%, BCE 85%, BSE 65%, compo 55 extract wherever used in the patent application refers to sition-3A, composition-4, composition-18 and composition the low polar gum resin extract obtained from any of the 7A at 10 ug/mL concentration. Boswellia species by any of the processes described. FIG. 4: Figure shows bar diagrammatic representations of 15. Boswellia oil or oily residue or Boswellia oil frac percentage inhibition of paw edema Volume in Freund's tion wherever used in the present application refers to Complete Adjuvant induced Sprague Dawley rats by 60 the total oil fraction/extract (comprising essential oils, Boswellia serrata low polar gum resin extract BSLPRE, 200 volatile oils and Boswellia low polar resin extract) mg/kg body weight (BW), Boswellia carterii low polar gum obtained from the gum resin of any of the Boswellia resin extract (BcLPRE, 200 mg/kg BW), Boswellia serrata species by any of the processes described. extract standardized to 85% total Boswellic acids (BSE85%, 16. Volatile oil or volatile fraction wherever used in the 200 mg/kg BW), Boswellia carterii extract standardized to 65 patent application refers to volatile oils obtained by 85% total Boswellic acids (BCE 85%, 200 mg/kg BW), steam distillation or vacuum distillation of any Boswellia Serrata extract standardized to 65% total Boswell Boswellia gum resin or Boswellia oil. US 8,551.496 B2 7 8 17. Phytochemical wherever used in the patent applica cial biological properties. In addition, BLPRE unexpectedly tion refers to a pure or semi-pure compound or com exhibited synergistic activity when combined with other bio pounds isolated from plants. logically active ingredients. 18. The terms biologically active ingredient(s) and func A representative procedure for obtaining Boswellia serrata tional ingredient(s), wherever used in the patent appli low polar gum resin extract (BSLPRE) comprises: cation, each refer to any pharmaceutically or dietetically a) Procuring the gum resin of Boswellia serrata. acceptable ingredient(s); compound(s), extract(s), frac b) extraction with an water immiscible organic solvent and tion(s), phytochemical(s) and their salts or mixtures the insoluble gum materials were separated by filtration thereof derived from plants/animals/microorganisms. and discarded, More particularly, these terms may each refer to any 10 herbal extract(s), dietary Supplement(s), antioxidants, c) washing the organic solvent extract repeatedly with dilute Vitamins, minerals, amino acids, fatty acids, essential aqueous alkali Solution to remove the acidic compounds, oils, fish oils, enzymes, Glucosamine, Chondroitin and d) washing the organic layer Successively with water and probiotics or mixtures thereof derived from plants/ani brine, mals/microorganisms. 15 e) evaporating the organic layer under vacuum at 60-70° C. to 19. Excipients or diluents’ or carriers or additives obtain an oily residue, wherever used in the patent application refer to one or f) the volatile components are then removed from the said oily more pharmaceutically or dietetically acceptable active residue under high vacuum and high temperature to obtain orinactive ingredients including but not limited to water, a viscous oil, which is referred herein after as Boswellia Saline, aqueous glucose solution, alcohol (e.g. ethanol), serrata low polar gum resin extract (BSLPRE). propylene glycol, polyethylene glycol, various animal Alternatively, the BSLPRE can also be prepared by a pro and vegetable oils, white soft paraffin, paraffin, wax, cess comprising: glucose, fructose, Sucrose, maltose, yellow dextrin, a) preparing the alcohol or hydroalcohol extract of Boswellia white dextrin, aerosol, microcrystalline cellulose, cal Serrata gum resin, cium Stearate, magnesium Stearate, Sorbitol, Stevioside, 25 b) partitioning the alcohol extract between an aqueous alkali corn Syrup, lactose, citric acid, tartaric acid, malic acid, Solution and a water immiscible organic solvent, Succinic acid, lactic acid, L-ascorbic acid, d1-alpha-to c) separation of the organic solvent layer, followed by evapo copherol, glycerin, propylene glycol, glycerin fatty rating the organic layer under vacuum at 60-70° C. to obtain ester, poly glycerin fatty ester, Sucrose fatty ester, Sorbi an oily residue, tan fatty ester, propylene glycol fatty ester, acacia, car 30 d) the volatile components are then removed from the said rageenan, casein, gelatin, pectin, agar, Vitamin B group, oily residue under high vacuum and high temperature to nicotinamide, calcium pantothenate, amino acids, cal obtain a viscous oil, which is referred herein after as cium salts, pigments, flavours and preservatives. Boswellia serrata low polar gum resin extract (BSLPRE). Boswellia Serrata and Boswellia carterii Low Polar Gum A representative procedure for obtaining Boswellia cart Resin Extract: 35 erii low polar gum resin extract (BcLPRE) comprises: The gum resin obtained from a Boswellia species, which a) procuring the gum resin of Boswellia carterii, may be, but is not limited to, Boswellia serrata, Boswellia b) extracting the gum resin with an water immiscible carterii, Boswellia papyrifera or mixtures thereof, is a com organic solvent and the insoluble gum materials were plex mixture comprising essential oil, Volatile oils, Boswellic separated by filtration and discarded, acids, low polar compounds, Sugars and polysaccharide frac 40 c) washing the organic solvent extract repeatedly with tion. The Boswellia Serrata, Boswellia carterii, and/or dilute aqueous alkali solution to remove the acidic com Boswellia papyrifera extracts widely available in the interna pounds, tional markets are acidic fractions separated from the gum d) washing the organic layer Successively with water and resin which are standardized to contain 65% or 85% total brine, Boswellic acids by titrimetric method of analysis. During the 45 e) evaporating the organic layer under vacuum at 60-70° C. execution of commercial process for regular Boswellia to obtain an oily residue. extracts derived from Boswellia Serrata/Boswellia Carterii/ f) the volatile components are then removed from the said Boswellia papyrifera (85% total Boswellic acids), the acidic oily residue under high vacuum and high temperature to fraction, which contains predominantly triterpene acids obtain a viscous oil, which is referred herein after as including Boswellic acids is separated from the rest of the 50 Boswellia carterii low polar gum resin extract gum resin components. The Sugars and other polymeric mate (BcLPRE). rials get separated out into the aqueous phase during the Alternatively, the BcLPRE can also be prepared by process enrichment process for total Boswellic acids. The remaining comprising: water immiscible low polar compounds, are separated as a a) preparing the alcohol or hydroalcohol extract of Boswellia Boswellia oil fraction or extract. These low polar compounds 55 carterii gum resin, are either absent or present at very low concentration in both b) partitioning the alcohol extract between an aqueous alkali commercial Boswellia extracts standardized to boswellic Solution and a water immiscible organic solvent, acids and Boswellia extracts selectively enriched in 3-O- c) separation of the organic solvent layer, followed by evapo acetyl-11-keto-B-Boswellic acid (AKBA). rating the organic layer under vacuum at 60-70° C. to obtain The Boswellia oil fraction or extract constitutes a signifi 60 an oily residue, cant component in Boswellia gum resin. However, it has very d) the volatile components are then removed from the said limited commercial utility and it is mostly discarded as a oily residue under high vacuum and high temperature to waste material. Potential utilization of this fraction or extract obtain a viscous oil, which is referred herein after as has been long overdue. The inventors found very unexpect Boswellia carterii low polar gum resin extract (BcLPRE). edly that Boswellia low polar gum resin extract (BLPRE), a 65 The representative processes for obtaining Boswellia low fraction obtained after removing the Volatile compounds polar gum resin extract (BLPRE) from Boswellia serrata, from the Boswellia oil fraction or extract, has several benefi Boswellia carterii are described above. However, a similar US 8,551.496 B2 10 process or processes can be applied to any of the gum resins BCE 85%, and BSE 65% at certain ratios showed synergistic obtained from Boswellia species for producing the low polar inhibition of 5-lipoxygenase enzyme. gum resin extract. The composition-3A (BsLPRE and BSE 85% in 1:2 ratio), In order to understand the chemical composition of BSL showed 27.12% inhibition at 10 ug/mL compared to 15.13% PRE, the inventors have carried out extensive separation of 5 and 21.04% inhibitions shown respectively by BSLPRE and BSLPRE using repeated column chromatography and high BSE 85% at the same concentrations. performance liquid chromatography (HPLC), and isolated The comparative 5-lipoxygenase inhibition shown by com several diterpenoid and triterpenoid compounds. The struc position-3A (BSLPRE and BSE 85% in 1:2 ratio), composi tures of the compounds were rigorously characterized using tion-4 (BcLPRE and BCE 85% in 1:2 ratio), composition-18 H NMR, 3C NMR, DEPT, HSQC and HMBC, Mass spec 10 (BcLPRE and BSE 85% in 1:2 ratio), composition-7A (BsL tral data. The compounds so obtained and identified are guiol PRE and BSE 65% in 1:2 ratio), along with those shown by (1), nephthenol (2), serratol (3), diterpene X (4), lupeol (5), individual ingredients/extracts are presented in FIG. 3. olean-12-ene-3?-ol (6), olean-12-ene-3C-ol (7), lanosta-8, The synergistic effects shown by composition-3A, compo 24-diene-3C-ol (8) and urs-12-ene-3C-ol (9) as depicted in sition-4, composition-18, composition-7A in vitro along with FIG. 1. The fraction, Boswellia serrata low polar gum resin 15 few other compositions were then put to test in an in vivo extract (BSLPRE) was then standardized to three or more of study in Freund's Complete Adjuvant induced arthritis model the phytochemical marker compounds selected from 1 to 9. of Sprague Dawley rats. The anti-inflammatory efficacy of The typical results obtained are summarized in the Table 1 composition-3A, composition-4, composition-18, composi and a typical chromatogram depicting the profile of BsLPRE tion-7A, composition-42 (BSLPRE and CLE 20% in 1:2 is presented in FIG. 2. However, the inventors have also found ratio), composition-26 (BSLPRE and CLE 95% in 1:2 ratio), that this composition of BSLPRE or any other Boswellia low composition-51 (BcLPRE and CAE 20% in 1:2 ratio) and polar gum resin extract composition (BLPRE) obtained from composition-35 (BcLPRE and CAE 95% in 1:2 ratio) were any other species may vary based on several factors such as evaluated in an in vivo study in Freund's Complete Adjuvant Boswellia species used, age of the plant, season of collection induced arthritis model of Sprague Dawley rats and compared of gum resin, geographic location and manufacturing process 25 their efficacy with the efficacy shown by the individual ingre employed. dients/extracts such as BSLPRE, BcLPRE, BSE 85%, BCE The foregoing results manifest that BSILPRE is a novel 85%, BSE 65%, CLE 20%, CLE 95%, CAE 20% and CAE composition comprising unique combination of sesquiterpe 95%. The rats of either sex were randomly selected and noids, diterpenoids and triterpenoids and other phytochemi divided into nineteen groups containing six animals per group cal(s). A compound tentatively identified as diterpene X (4) 30 and the treatment groups were supplemented daily with 200 and compounds guiol (1), nepthenol (2) and Lanosta-8.24 mg/kg body weight (BW) of one of BsLPRE, BcLPRE, BSE diene-3C-ol (8) are not known to be metabolites of Boswellia 85%, BCE 85%, BSE 65%, CLE 20%, CLE 95%, CAE 20%, serrata gum resin. These results suggest that BSLPRE is a CAE 95%, composition-3A, composition-4, composition-18, novel composition. Surprisingly Bs PRE also exhibited composition-7A, composition-42, composition-26, composi potent biological properties. BSLPRE potently inhibited 5-li 35 tion-51 and composition-35 for 14 days. The positive control poxygenase enzyme (Table 2). It showed 15.13% inhibition group was supplemented daily with Prednisolone at 10 mg/kg of 5-lipoxygenase at 10 g/mL concentration. body weight. At the 14th day, Freund's Complete Adjuvant The identification of the composition of low polar gum (FCA) was injected Subcutaneously in the Sub-plantar region resin extract obtained from various Boswellia species such as of the left hind paw of each animal. The experiment was Boswellia Carterii, Boswellia papyrifera is under process. It 40 terminated on 28 day. Blood samples were collected from is contemplated that the low polar gum resin extract of these each animal at regular intervals and paw Volumes were mea as well as other Boswellia species comprise a composition sured by Plethysmography equipment on the day of FCA having some similarity to that of Boswellia serrata. However, injection and after 13 days of FCA inoculation. The differ the low polar gum resin extract of Boswellia carterii ence in Volume of paw edema is considered as the inflamma (BcLPRE) has shown biological activity and synergistic 45 tory response. The in Vivo anti-inflammatory response of effect very similar to that exhibited by BsLPRE as summa BsLPRE, BcLPRE, BSE 85%, BCE 85%, BSE 65%, CLE rized in the following in vitro and in vivo studies. The experi 20%, CLE 95%, CAE 20%, CAE 95%, composition-3A, mental studies are discussed in the examples. composition-4, composition-18, composition-7A, composi Synergistic Composition(s) Comprising Boswellia Low tion-42, composition-26, composition-51, composition-35 Polar Gum Resin Extract (BLPRE): 50 and Prednisolone were estimated by calculating the percent The inventors have conducted several cell based and age inhibition of paw edema when compared to the CMC enzyme based in vitro studies on a broad array of Boswellia Supplemented control. extracts, including Boswellia serrata low polar gum resin The treatment groups Supplemented with 200 mg/kg body extract (BSLPRE) and Boswellia carterii low polar gum resin weight of Boswellia serrata low polar gum resin extract extract (BcLPRE). Additional studies were performed on 55 (BSLPRE) and 200 mg/kg body weight of Boswellia serrata Boswellia extracts comprising polar compounds such as extract standardized to 85% total Boswellic acids (BSE 85%) Boswellic acids, including Boswellia serrata extract stan showed 23% and 30% reduction in paw edema respectively. dardized to 85% Boswellic acids (BSE 85%), Boswellia ser However, the treatment group Supplemented with composi rata extract standardized to 65% Boswellic acids (BSE 65%), tion-3A (BsLPRE and BSE 85% in 1:2 ratio) at the same dose and Boswellia carterii extract standardized to 85% Boswellic 60 level showed better reduction and achieved 42% reduction in acids (BCE 85%). Several other herbal extracts were also paw edema Volume. The positive control group Supplemented tested. The individual extracts and different combinations of with Prednisolone exhibited 46% inhibition at 10 mg/kg dose these extracts were tested for their efficacy to inhibit 5-lipoxy level. Similarly, the other inventive compositions composi genase enzyme (5-LOX). tion-4, composition-18, composition-7A, composition-42, It was found very Surprisingly that the compositions com 65 composition-26, composition-51 and composition-35 also prising either Bs PRE or BcLPRE in combination with any exhibited synergistic effects as summarized in FIG. 4 and one of the following standardized extracts such as BSE 85%, Table 3 confirming the observed in vitro results. US 8,551.496 B2 11 12 Therefore, the foregoing data shows that the compositions In another aspect, the disclosure provides a process for comprising either BsLPRE or BcLPRE in combination with a producing Boswellia low polar resin extract (BLPRE) com standardized extract of Boswellia species such as, BSE 85%, prising the following steps: BCE 85% and BSE 65% or a standardized extract of Curcuna a) extraction of the gum resin of Boswellia species with a species such as CLE 20%, CLE 95%, CAE 20% and CAE water immiscible organic solvent and filtering the extract 95% in the ratio of 1:2 are more potent as anti-inflammatory carefully to remove the insoluble resin material. agents compared to the efficacy shown by the individual b) washing the organic solvent extract repeatedly with an components at the same dose levels, manifesting an unex aqueous alkali Solution Such as aqueous potassium hydroxide pected synergistic association between these extracts. c) washing the organic layer obtained after the alkali wash, Boswellia serrata and Boswellia carterii low polar gum 10 with water and brine, resin extracts (BSLPRE and BcLPRE respectively) obtained d) evaporating the said organic layer under vacuum and high after removing the Volatile compounds have been used to temperature to obtain the oily residue (Boswellia oil), demonstrate the present disclosure. However, Boswellia oil e) removing the Volatile compounds from the said oily residue fraction obtained from any of the Boswellia species or volatile under high Vacuum and high temperature to obtain Boswellia fraction obtained from any of the Boswellia species or frac 15 low polar resin extract (BLPRE). tions obtained after partially removing the volatiles from The water immiscible organic solvent used for extraction Boswellia oil or mixtures thereof can also be used for making may be, but is not limited to 1,2-dichloroethane, hexane, the compositions and synergistic composition(s) of the dis dichloromethane, chloroform, ethyl acetate, n-butanol, closure, and for obtaining the intended therapeutic/health methyl iso-butyl ketone (MIBK), hydrocarbon solvents, or benefits in warm blooded animal(s). combinations thereof. The Boswellia low polar gum resin extracts, used for dem The alkali solution used for washing the organic Solvent onstrating the present disclosure, have been obtained from extract can be selected from Group-I or Group-II metal Boswellia Serrata and Boswellia carterii and the names BsL hydroxides, including but not limited to Sodium hydroxide, PRE and BcLPRE respectively have been chosen arbitrarily Potassium hydroxide, Calcium hydroxide and Magnesium for them. However, the inventors have found that low polar 25 hydroxide or mixtures thereof. gum resin extract (BLPRE) with similar chemical and bio In another aspect, an alternative process for producing logical properties can also be derived from other Boswellia BLPRE comprise: species using similar processes as shown in Example-1 and a) preparing the alcohol or hydroalcohol extract of Boswellia Example-2. gum resin, Commercially available Boswellia serrata extract and 30 b) partitioning the alcohol extract between an aqueous alkali Boswellia carterii extract standardized to 85% Boswellic Solution and a water immiscible organic solvent, acids have been used for making the composition(s) to dem c) separation of the organic solvent layer, followed by evapo onstrate the present disclosure. However, any Boswellia ration of the solvent to obtain oily residue (Boswellia oil), extract(s) or fraction(s) or Boswellia extracts standardized to d) removal of volatile compounds from the said oily residue at least one or more Boswellic acids or their salts; extract(s)/ 35 under high temperature and high vacuum to obtain Boswellia fraction(s) standardized to 50-100% total Boswellic acids by low polar gum resin extract (BLPRE). titrimetric method of analysis or extract(s)/fraction(s) stan In another aspect, a further alternative process for produc dardized to 30%-100% total Boswellic acids by HPLC ing Boswellia low polar gum resin extract (BLPRE) com method of analysis or extract(s)/fraction(s) having 3-O- prise, acetyl-11-keto-B-Boswellic acid (AKBA) concentration in 40 a) extracting the gum resin of Boswellia species with alco the range of 0.1-99% can also be used to make the composi hol or hydro alcohol, tions described in the present disclosure. b) evaporating the organic solvent to an optimum level of The BLPRE produced from Boswellia serrata or Boswellia total solids and then carterii when combined with an array of Boswellia or Cur c) adjusting the pH to the alkaline side, preferably pH 9-12, cuma extracts showed synergistic activity. However, BLPRE 45 d) repeatedly extracting the Solution with an organic Sol produced from other Boswellia species is also useful in pre Vent, paring the synergistic composition(s). e) evaporating the organic solvent under vacuum and high temperature to obtain the oily residue (Boswellia oil), DESCRIPTION OF VARIOUSEMBODIMENTS f) evaporating the volatiles from the said oily residue under 50 high vacuum and high temperature to obtain BLPRE. In an important aspect, the disclosure provides a Boswellia The alcohol used for extraction can be selected from the low polar gum resin extract (BLPRE) comprising novel phy group comprising but not limited to methanol, ethanol and tochemical composition of sesquiterpenes, diterpenes, triter propanol or their suitable combination thereof. penes, and other phytochemical(s) obtained from Boswellia In various embodiments, the disclosure provides the Syn gum resin. 55 ergistic composition(s) comprising Boswellia low polar gum In another aspect, the disclosure provides Boswellia low resin extract (BLPRE) and at least one component selected polar gum resin extract (BLPRE) where in the gum resin can from the extract(s) or fraction(s) or phytochemical(s) or their be obtained/originated from any of the Boswellia species salt(s) or mixtures thereof derived from Boswellia species. In including but not limited to Boswellia serrata, Boswellia Some embodiments, the disclosure provides the Synergistic carterii and Boswellia papyrifera or mixtures thereof. 60 composition(s) comprising Boswellia low polar gum resin In another aspect, the disclosure provides a Boswellia low extract (BLPRE) and at least one component selected from polar gum resin extract from Boswellia serrata gum resin, boswellic acid containing extracts derived from Boswellia wherein the said extract comprises phytochemical marker species. compounds selected from but not limited to guiol (1), neph In other aspects, the disclosure provides synergistic com thenol (2), serratol (3), diterpene X (4), lupeol (5), olean-12 65 position(s) comprising BLPRE and at least one component ene-3?-ol (6), olean-12-ene-3C-ol (7), lanosta-8.24-diene selected from the extract(s) or fraction(s) or phytochemical(s) 3C-ol (8) and urs-12-ene-3C-ol (9). or their salt(s) or mixtures thereof derived from Curcuma US 8,551.496 B2 13 14 species. In some aspects, the disclosure provides Synergistic ylcurcumin, tetrahydro-curcumin, composition(s) comprising Boswellia low polar gum resin tetrahydrodemethoxycurcumin, tetrahydro bisdemethoxy extract (BLPRE); and at least one component selected from curcumin, arturmerone and their salts obtained naturally or by curcuminoid-containing extracts derived from Curcuna spe synthesis or by semi-synthesis. C1GS. In another aspect, the disclosure provides process for pro In some aspects, the disclosure provides synergistic com ducing synergistic composition(s) comprising the steps: position(s) comprising Boswellia low polar gum resin extract (a) extraction of the gum resin of Boswellia serrata or (BLPRE); at least one component selected from the boswellic Boswellia carterii or Boswellia papyrifera with a water acid containing extracts derived from Boswellia species; and immiscible organic solvent, at least one component selected from curcuminoid-contain 10 (b) filtering the extract carefully to remove the insoluble ing extracts derived from Curcuma species. resin material, In various aspects, the disclosure provides a Boswellia low (c) washing the organic solvent extract repeatedly with an polar gum resin extract, which is low polar, obtained after aqueous alkali solution Such as aqueous potassium selectively removing the acidic and Volatile compounds. hydroxide, In another aspect, the disclosure provides the use of one or 15 more components selected from Boswellia oil fraction (d) washing the said alkali washed organic solvent extract obtained from any of the Boswellia species or volatile fraction with successively water and brine, obtained from any of the Boswellia species or fractions (e) evaporating the organic layer under vacuum and high obtained after partially removing the volatiles from Boswellia temperature to obtain an oily residue, oil in place of BLPRE for preparing composition(s) described (f) removing the Volatile compounds from the said oily in the patent application. residue under high vacuum and high temperature to In another aspect, the disclosure provides the Boswellia obtain the Boswellia low polar resin extract (BLPRE). extract(s) or fraction(s) or pure phytochemicals or their salts (g) separately, obtaining a Boswellia derived component or their mixtures thereof preferably obtained from Boswellia Selected from the extract(s) or fraction(s) or pure com serrata or Boswellia carterior Boswellia papyrifera for pre 25 pound(s), extracts/fractions selectively enriched in one paring the compositions with BLPRE. or more boswellic acid(s) or mixtures thereof, In further aspects, the disclosure provides the Synergistic (h) combining the said BLPRE and at least one Boswellia composition(s) comprising BLPRE with one or more selected derived component(s) in a desired ratio to obtain syner from the Boswellia extract(s), fraction(s) and extracts/frac gistic composition(s), tions enriched in total Boswellic acids in the range of 30 (i) optionally mixing the said composition(s) with one or 50-100%, by the titrimetric method of analysis or 30-100%, more biologically active ingredients, functional ingredi by HPLC method of analysis. ents, excipients, diluents, carriers and additives. In yet another aspect, the disclosure provides Synergistic In another aspect, the disclosure provides process for pro composition(s) comprising BLPRE and one or more compo ducing synergistic composition(s) comprising the steps: nent(s) selected from the extract(s), fraction(s) and phy 35 (a) extraction of the gum resin of Boswellia serrata or tochemical(s) comprising Boswellic acids either individually Boswellia carterii or Boswellia papyrifera with a water or in combination selected from C.-Boswellic acid, B-Boswell immiscible organic solvent, lic acid, 3-O-acetyl-C.-Boswellic acid, 3-O-acetyl-3-Boswel (b) filtering the extract carefully to remove the insoluble lic acid, 3-O-acetyl-11-keto-O-Boswellic acid, 11-keto-B- resin material, Boswellic acid and 3-O-acetyl-11-keto-B-Boswellic acid and 40 (c) washing the organic solvent extract repeatedly with an their salts. aqueous alkali solution Such as aqueous potassium In another aspect, the disclosure provides Synergistic com hydroxide, position(s) comprising BLPRE and one or more compo (d) washing the said alkali washed organic solvent extract nent(s) selected from the extract(s), fraction(s) and phy successively with water and brine, tochemical(s) comprising Boswellic acids either individually 45 (e) evaporating the organic layer under vacuum and high or in combination selected from C.-Boswellic acid in the range temperature to obtain an oily residue, of 0.1-20%, B-Boswellic acid in the range of 0.1-50%, 3-O- (f) removing the Volatile compounds from the said oily acetyl-C.-Boswellic acid in the range of 0.1-20%, 3-O-acetyl residue under high vacuum and high temperature to B-Boswellic acid in the range of 0.1-99%, 3-O-acetyl-11 obtain the Boswellia low polar resin extract (BLPRE). keto-O-Boswellic acid 0.1-20%, 11-keto-B-Boswellic acid in 50 (g) separately, obtaining a Curcuna derived component(s) the range of 0.1-99% and 3-O-acetyl-11-keto-B-Boswellic selected from the extract(s) or fraction(s), extracts/frac acid in the range of 0.1-99% and their salts. tions enriched with one or more Curcuminoids, pure In another aspect the disclosure provides, compositions Curcuminoid compounds or mixtures thereof, comprising BLPRE and one or more selected from extract(s), (h) combining the said BLPRE and at least one Curcuma fraction(s), phytochemical(s) and their salts derived from the 55 derived component(s) in a desired ratio to obtain syner Curcuna species. gistic composition(s), In another aspect the disclosure provides, composition(s) (i) optionally mixing the said composition(s) with one or comprising BLPRE and at least one or more component(s) more biologically active ingredients, functional ingredi selected from the extract(s), fraction(s), phytochemical(s), ents, excipients, diluents, carriers and additives. and their salts derived from Curcuma species, extracts/frac 60 In another aspect, the disclosure provides Synergistic com tions enriched/standardized to Curcuminoids either individu position(s) comprising preferably 5%-95% by weight of ally or in combination in the range of 20-99% by HPLC Boswellia low polar resin extract (BLPRE) and preferably method of analysis. 95%-5% by weight of at least one Boswellia derived compo In another aspect the disclosure provides, compositions nent selected from extract(s), fraction(s), extracts and frac comprising BLPRE and one or more Curcuma derived com 65 tions standardized to one or more boswellic acids, pure ponents selected from curcumin, demethoxycurcumin, bis boswellic acid(s), phytochemical(s) and their salts or mix demethoxycurcumin, monodemethylcurcumin, bisdemeth tures thereof. US 8,551.496 B2 15 16 In another aspect, the disclosure provides Synergistic com In another aspect, the herbal ingredient(s) used for prepar position(s) comprising more preferably 20%-80% by weight ing composition(s) include extracts/fractions/phytochemi of Boswellia low polar resin extract (BLPRE) and more pref cals derived from plants selected from but not limited to erably 80%-20% by weight of at least one Boswellia derived Withania Sonnifera, Garcinia mangostana, Garcinia Cambo component selected from extract(s), fraction(s), extracts and gia, Piper nigrum, Piper betle, Piper longum, Bacopa mon fractions standardized to one or more boswellic acids, pure niera, Centella asiatica, Amorphophalus campanulatus, boswellic acid(s), phytochemical(s) and their salts or mix Amorphophallus konjac, Emblica officinalis, Holoptelea tures thereof. integrifolia, Ocimum tenuiflorum, Annona squamosa and In another aspect, the disclosure provides Boswellia low Sphaeranthus indicus. polar gum resin extract (BLPRE), Boswellia oil, Boswellic 10 In another aspect, the disclosure provides composition(s) acid(s), extract(s), fraction(s), extracts and fractions enriched for the prevention, control or treatment of one or more dis in one or more boswellic acids, phytochemical(s) and their eases or disorders in warm blooded animal(s). salts derived from Boswellia species, wherein the Boswellia In another embodiment of the disclosure excipients/dilu species include but not limited to Boswellia serrata, ents/additives/sweetening agents/flavoring agents/wetting Boswellia carterii, Boswellia papyrifera, Boswellia sacra, 15 agents/absorbents/solution retarding agents include but not Boswellia ameero, Boswellia bullata, Boswellia dalzielii, limited to distilled water, Saline, aqueous glucose solution, Boswellia dioScorides, Boswellia elongata, Boswellia fre alcohol (e.g. ethanol), propylene glycol, polyethylene glycol, reana, Boswellia nana, Boswellia neglecta, Boswellia various animal and vegetable oils, white Soft paraffin, paraf Ogadensis, Boswellia pirottae, Boswellia popoviana, fin, wax, glucose, fructose. Sucrose, maltose, Saccharin, yel Boswellia rivae and Boswellia Socotrana. low dextrin, white dextrin, aerosol, microcrystalline cellu In another aspect of the disclosure, the composition of lose, calcium Stearate, magnesium Stearate, Sorbitol, BsLPRE or BLPRE varies based on several factors such as Stevioside, corn Syrup, lactose, citric acid, tartaric acid, malic Boswellia species used, age of the plant, season of collection acid, Succinic acid, lactic acid, L-ascorbic acid, d1-alpha of gum resin, geographic location and manufacturing process tocopherol, glycerin, propylene glycol, glycerin fatty ester, employed. 25 poly glycerin fatty ester. Sucrose fatty ester, Sorbitan fatty In another aspect, the disclosure provides the Synergistic ester, propylene glycol fatty ester, acacia, carrageenan, compositions comprising preferably 5%-95% by weight of casein, gelatin, pectin, agar, Vitamin B group, nicotinamide, Boswellia low polar resin extract (BLPRE) and preferably calcium pantothenate, amino acids, calcium salts, cetyl alco 95%-5% by the weight of at least one Curcuma derived com hol, glyceryl monostearate, kaolin, betonite clay pigments, ponent selected from extract(s), fraction(s), extracts/fractions 30 peppermint, methyl salicylate, orange flavor, Vanilla flavor standardized to one or more curcuminoids, pure curcumi and preservatives alone or in a suitable combination thereof. noid(s), phytochemical(s) and their salts or mixtures thereof. In another aspect, the disclosure provides for administra In another aspect, the disclosure provides Synergistic com tion of Boswellia low polar gum resin extract (BLPRE) alone position(s) comprising more preferably 20%-80% by weight or its composition(s) in comminuted form or in unmodified of BLPRE and more preferably 80%-20% by weight of at 35 form in a suitable dosage form selected from but not limited least one Curcuna derived component selected from to an infusion Solution, injection Solution, tablet, capsule, extract(s), fraction(s), extracts and fractions standardized to cream, gel, granules, precipitate, extract, liquid, Syrup, shots, one or more curcuminoids, pure curcuminoid(s), phy exudates, ointment, enema, medicinal pack, topical patches, tochemical(s) and their salts or mixtures thereof. controlled release tablets, controlled release capsules or food In another aspect, the disclosure provides extract(s), frac 40 Supplement. tion(s), extract(s)/fraction(s) selectively enriched in curcumi In another aspect, the disclosure provides for formulation noids, Curcuminoids, phytochemical(s) and their salts of Boswellia low polar gum resin extract (BLPRE) alone or its derived from Curcuma species, wherein the Curcuna species composition(s) into Suitable forms including but not limited include but not limited to Curcuna longa, Curcuma aro to oral agents such as tablets, capsules, soft capsules, hard matica, Curcuma Zedoaria, Curcuma domestica, Curcuna 45 capsules, pills, granules, powders, emulsions, Suspensions, aeruginosa, Curcuma albicoma, Curcuma albiflora, Cur syrups and pellets; as parenteral agents such as injection cuma alismatifolia, Curcuna angustifolia, Curcuna elata, Solution, drops and Suppositories; and as transdermal agents Curcuna ferruginea, Curcuna flaviflora, Curcuma yunnan Such as patches, topical creams and gel and food ingredients ensis, and Curcuma Zedoaroides. or beverages. In another major aspect, the disclosure provides composi 50 In another aspect the disclosure provides use of the com tion(s) comprising Boswellia low polar resin extract (BL position(s) for the prevention, control and treatment of disor PRE) and one or more component(s) selected from biologi ders or diseases in warm-blooded animals in need thereof. cally active ingredient(s), functional ingredient(s), exci In another aspect, the disclosure provides a method of pient(s), diluent(s), carrier(s) and additive(s). using a therapeutically effective amount of Boswellia low In another aspect, the Biologically active ingredients used 55 polar gum resin extract (BLPRE) alone or its composition(s) for preparing the composition(s) include but not limited to for the prevention, control and treatment of diseases or dis pharmaceutically or dietetically acceptable active ingre orders selected from but not limited to inflammation, meta dient(s), anti-inflammatory agents, anti-obese agents, anti bolic disorders, inflammatory disorders, asthma, atheroscle diabetic agents, anti-arthritic agents, anti-asthmatic agents, rosis, endothelial dysfunction, osteoarthritis, rheumatoid anti-cancer agents, compound(s), extract(s), fraction(s), phy 60 arthritis, allergic rhinitis, dermatitis, psoriasis, cystic fibrosis, tochemical(s) and their salts or mixtures thereof derived from inflammatory bowel diseases, multiple Sclerosis, diabetes, plants, animals or microorganisms. memory loss, neurological disorders, cartilage degradation, In another aspect, the functional ingredient(s) used for aging, skin disorders, disorders in cholesterol levels (LDL, preparing composition(s) include but not limited to herbal VLDL and HDL), hyper triglyceridemia, hyperlipidemia, ingredient(s), dietary Supplements, antioxidants, vitamins, 65 hypercholesterolemia, hypertension, high blood pressure, minerals, amino acids, fatty acids, essential oils, fish oils, immune disorders, coronary heart disease, vasculitis, ulcer enzymes, Glucosamine, chondroitin and probiotics. ative colitis, gastrointestinal allergies, nephritis, conjunctivi US 8,551.496 B2 17 18 tis, chronic obstructive pulmonary disease, occupational residue (50 g) was dissolved in ethyl acetate (400 mL) and asthma, eczema, bronchitis, hay fever, hives, adult respiratory extracted thrice with 1N KOH (3x100 mL). The organic layer distress syndrome, allergic disorders and for conditions like was washed with water (2x200 mL) and brine (200 mL) and wheezing, dyspnea, non productive cough, chest tightness, evaporated to obtain oily residue (Boswellia oil). The volatile neck muscle tightness, rapid heart rate, chest pain, infectious compounds were evaporated from the oil under high vacuum diseases, osteoporosis, joint pain, joint discomfort, cognitive at 75-85°C. to obtain 22 g of BsLPRE. disorders and several other conditions associated thereof in The BSLPRE was subjected to column chromatography warm blooded animals in need thereof. over normal silica gel using solvents of increasing polarity In another aspect, administration ofatherapeutically effec starting from hexane to hexane/ethyl acetate mixtures to ethyl tive amount of Boswellia low polar gum resin extract (BL 10 acetate. The identical fractions were combined based on TLC PRE) alone or its composition(s) for the prevention, control and the combined fractions were subjected individually to and treatment of disease conditions related to or associated repeated column over silica gel using mixtures of hexane/ with inflammation, which include but not limited to asthma, ethyl acetate or hexanefacetone as eluants to obtain pure occupational asthma, eczema, bronchitis, hay fever, hives, compounds. Some of the impure fractions were further sub rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic 15 jected to preparative HPLC using a reversed phase C18 silica arthritis, osteoarthritis, refractory rheumatoid arthritis, column to obtain pure compounds. The structures of indi chronic non-rheumatoid arthritis, osteoporosis, coronary vidual compounds were established by analyzing the "H heart disease, atherosclerosis, endothelial dysfunction, mul NMR, 'C NMR, DEPT, HSQC and HMBC and mass spec tiple Sclerosis, vasculitis, nephritis, uveitis, glomerulonephri tral data and then comparing the data with that of known tis, systemic lupus erythematosis, post-angioplasty resteno compounds. Nine of the prominent compounds are identified sis, ulcerative colitis, conjunctivitis, dermatitis, psoriasis, as guiol (1), nephthenol (2), Serratol (3), diterpene X (4), cystic fibrosis, adult respiratory distress syndrome, IBS (in lupeol (5), olean-12-ene-3?-ol (6), olean-12-ene-3C-ol (7), flammatory bowel syndrome), IBD (inflammatory bowel dis lanosta-8.24-diene-3C-ol (8) and urs-12-ene-3C.-ol (9) as ease), chronic obstructive pulmonary disease, adult respira depicted in FIG.1. The pure compounds were then utilized to tory distress syndrome, allergic rhinitis, gastrointestinal 25 standardize the Boswellia serrata low polar extract (BLPRE) allergies, allergic disorders and for conditions like wheezing, using HPLC method. The novel composition of BLPRE, dyspnea, nonproductive cough, chest tightness, neck muscle evaluated based on analytical HPLC method, along with the tightness, rapid heart rate, joint pain, and delayed-type hyper retention times (R) is summarized in Table 1. The HPLC sensitivity in warm blooded animals in need thereof. chromatogram for BLPRE is depicted in FIG. 2. In another aspect, the disclosure provides Boswellia low 30 Guaiol (1): polar gum resin extract (BLPRE) alone or its composition(s) H NMR (CDC1, 400 MHz): 8 2.57-2.53 (1H, m), 2.46 for the amelioration of one or more biological markers, which 2.39 (1H, m), 2.33-2.30 (1H, m), 2.28-2.22 (1H, m), 2.09 include but not limited to 5-lipoxygenase (5-LOX), 5-Li 1.89 (2H, m), 1.84-1.75 (2H, m), 1.67-1.52 (2H, m), 1.48 poxygenase activating protein (FLAP), Macrophage/Adipo 1.28 (3H, m), 1.18 (6H, s), 1.03 (3H, d, J=7.2 Hz), 0.99 (3H, cyte Fatty acid binding protein (aP2), IFN-y, IL-4, ICAM, 35 d, J=6.8 Hz); 'CNMR (CDC1, 100 MHz): & 140.98, 140.02, VCAM, MMPs, TNFC, NFkB and IL-1 B by composition(s) 73.80, 49.84, 45.10, 35.27, 33.83, 33.32, 31.28, 29.20, 27.35, in warm blooded animals in need thereof. 27.11, 26.27, 19.61, 19.26. In another aspect, the disclosure provides a method of use Nephthenol (2): of Boswellia low polar gum resin extract (BLPRE) alone or its 'HNMR (CDC1,400 MHz): 85.12(1H, t, J=7.0Hz), 5.00 composition(s) for the amelioration of one or more biological 40 (1H, t, J=6.4 Hz), 4.94 (1H, t, J=6.4 Hz), 2.20 (2H, m), 2.14 markers, which include but not limited to 5-lipoxygenase (2H, m), 2.12 (1H, m), 2.07 (2H, m), 2.03 (2H, m), 2.00 (2H, (5-LOX), 5-Lipoxygenase activating protein (FLAP), Mac m), 1.90 (1H, dd, J=14.0, 7.0 Hz), 1.65 (1H, m), 1.57 (6H, s), rophage/Adipocyte Fatty acid binding protein (aP2), IFN-y, 1.56 (3H, s), 1.34 (1H, m), 1.28 (1H, m), 1.20 (6H, s); 'C IL-4, ICAM, VCAM, MMPs, TNFo, NFkB and IL-1B by NMR (CDC1, 100 MHz): & 134.09, 133.39, 133.08, 125.98, composition(s) in warm blooded animals in need thereof. 45 125.80, 125.02, 73.94, 48.59, 39.42, 38.88, 37.81, 31.93, 29.69, 28.54, 28.34, 27.70, 27.57, 27.35, 24.73, 24.07, 15.61, EXAMPLES 15.58, 15.33. Mass 290 CHO Diterpene X (4) Example 1 "H NMR (CDC1), 400 MHz: 86.17 (1H, dd, J=10.8, 15.2 50 Hz), 5.78 (1H, d, J=7.2 Hz), 5.28 (1H, d, J=15.2 Hz), 4.87 Preparation of Boswellia serrata Low Polar Gum (1H, m), 4.41 (1H, d. J=11.2 Hz), 2.44 (1H, m), 2.26 (1H, dt, Resin Extract (BsLPRE) J=3.2, 11.6Hz), 2.11 (1H, m), 2.20 (2H, m), 1.75 (3H, s), 1.75 (6H, s), 1.72 (1H, d) 1.66 (3H, s), 1.60 (2H, m), 1.49 (3H, d, The Boswellia serrata gum resin (100 g) was dispersed in J=0.8 Hz) 1.34 (1H, m), 1.19 (3H, s), 0.94 (1H, m); 'C 600 mL of methyl isobutyl ketone (MIBK) solvent and stirred 55 NMR(CDC1), 100 MHz: & 12.05, 16.55, 18.22, 20.80, 25.84, at room temperature for 60 min. The insolublegum materials 26.00, 26.45, 28.77, 29.66, 30.58, 37.08, 41.15, 12148, were separated by filtration. The MIBK solution was 125.08, 125.12, 129.10, 132.05, 140.50, 141.89. extracted repeatedly with 2% KOH solution (3x200 mL) to Lanosta-8.24-diene-3C.-ol (8): remove the acidic compounds. The MIBK layer was then H NMR (CDC1,400 MHz): 85.10 (1H, t, J=6.8 Hz), 3.43 washed successively with water (400 mL) and brine (200 60 (1H, t, J–2.4 Hz), 2.12-1.85 (8H, m), 1.71 (2H, m), 1.65 (3H, mL). The MIBK layer was evaporated under vacuum at s), 1.59 (3H, s), 1.65-1.29 (10H, m), 1.26 (3H, s), 1.213-1.16 60-70° C. and the volatile components are then removed from (1H, m), 0.97 (3H, s), 0.96 (3H, s), 0.92 (3H, d, J=6.4 Hz), the oily residue under high vacuum at 75-85° C. to obtain 0.87 (6H, s), 0.77 (3H, s): 'C NMR (CDC1, 100 MHz): 8 BsLPRE as viscous oil (12 g). 134.44, 133.42, 130.87, 125.35, 76.02, 50.24, 50.09, 44.92, Alternatively, the gum resin (250 g) collected from 65 44.20, 37.73, 37.27, 36.48, 36.36, 30.92, 29.88, 29.72, 28.09, Boswellia serrata was extracted with methanol (300 mLX3) 27.31, 25.94, 25.70, 25.01, 24.43, 22.30, 21.46, 20.00, 18.90, and the combined methanol extract was concentrated. The 18.75, 17.63, 15.60. US 8,551.496 B2 19 20 TABLE 1. Example 4 Composition of Boswellia serrata Boswellia Carterii Extract Standardized to 50-100% low polar gun resin extract (BSLPRE Total Boswellic Acids (Titrimetric Method) S. No Test substance R, in min Percentage Boswellia carterii extracts standardized to 85% or 65% 1 Guiol (1) 4.5 O.96 2 Nephthenol (2) 7.087 2.01 total Boswellic acids by titrimetric method of analysis can be 3 Serratol (3) 8.027 13.32 prepared using a procedure described in Example 3 for 4 Diterpene X (4) 15.777 O.12 Boswellia serrata. For example, by extracting the gum resin 5 Lupeol (5) 26.901 O.O6 10 6 Olean-12-ene-3?-ol (6) 31.460 1.29 of Boswellia carterii using a water immiscible solvent and 7 Olean-12-ene-3C-ol (7) 33.718 5.36 then selectively extracting the acidic compounds from the 8 Lanosta-8.24-diene-3C-ol (8) 35.371 1.34 organic solvent extract using aqueous alkali solution through 9 Urs-12-ene-3C-ol (9) 37.2O7 4.SS phase separation. Finally acidification of the alkali solution to precipitate the Boswellic acids followed by filtration and 15 vacuum drying of the solid to yield Boswellia carterii extract Example 2 standardized to 85% total boswellic acids (BCE85%). Boswellia Carterii extracts standardized to a selected concen Preparation of Boswellia carterii Low Polar Gum tration of total Boswellic acids in the range of 50-100% by Resin Extract (BcLPRE) titrimetric method of analysis or 30-100% by HPLC method of analysis can be obtained by purification of the Boswellia The Boswellia carterii gum resin (100 g) was dispersed in carterii gum resin or Boswellia carterii extracts or by dilution 600 mL of methyl isobutyl ketone (MIBK) solvent and stirred of higher grade material. at room temperature for 60 min. The insolublegum materials Example 5 were separated by filtration. The MIBK solution was 25 extracted repeatedly with 2% KOH solution (3x200 mL) to Preparation of Composition-1 remove the acidic compounds. The MIBK layer was then washed successively with water (400 mL) and brine (200 Composition-1 was prepared by mixing unit doses of the mL). The MIBKlayer was evaporated under reduced pressure following components; one part of Boswellia serrata low at 60-70° C. and the volatile components are then removed 30 polar gum resin extract (BSLPRE) (1 g) and one part of from the oily residue under high vacuum at 75-85° C. to Boswellia Serrata extract standardized to 85% total Boswell obtain BcLPRE as a viscous oil (9.5 g). lic acids (BSE 85%) (1 g). Alternatively, the gum resin (250 g) collected from Boswellia carterii was extracted with methanol (300 mLX3) Example 6 and the combined methanol extract was concentrated. The 35 residue (50 g) was dissolved in ethyl acetate (400 mL) and Preparation of Composition-2 extracted thrice with 1N KOH (3x100 mL). The organic layer was washed with water (2x200 mL) and brine (200 mL) and Composition-2 was prepared by mixing unit doses of the evaporated to obtain oily residue. The volatile compounds following components; one part of Boswellia carterii low were evaporated from the oil under high vacuum at 75-85°C. 40 polar gum resin extract (BcLPRE) (1 g) and one part of to obtain 17.75 g of BcLPRE. Boswellia carterii extract standardized to 85% total Boswell lic acids (BCE 85%) (1 g). Example 3 Example 7 45 Boswellia Serrata Extract Standardized to 50-100% Preparation of Composition-3A Total Boswellic Acids by Titrimetric Method or to 30-100% Total Boswellic Acids by HPLC Method of Composition-3A was prepared by mixing unit doses of the Analysis following components; one part of Boswellia serrata low 50 polar gum resin extract (BSLPRE) (1 g) and two parts of Boswellia Serrata extracts standardized to 85% or 65% Boswellia Serrata extract standardized to 85% total Boswell total Boswellic acids by titrimetric method of analysis are lic acids (BSE 85%) (2 g). commercially available. Alternately, these extracts can be prepared using a known procedure. For example, by extract Preparation of Composition-3B ing the gum resin of Boswellia serrata using a water immis 55 cible organic solvent and then selectively extracting the acidic Composition-3B was prepared by mixing unit doses of the compounds from the organic solvent extract using aqueous following components; one part of Boswellia serrata low alkali Solution through phase separation. Finally acidification polar gum resin extract (BSLPRE) (1 g) and two parts of of the alkali solution to precipitate the Boswellic acids fol Boswellia carterii extract standardized to 85% total Boswell lowed by filtration and vacuum drying of the resultant solid to 60 lic acids (BCE 85%) (2 g). yield Boswellia serrata extract standardized to 85% Boswel lic acids (BSE85%). Boswellia serrata extracts standardized Example 8 to a selected concentration of total Boswellic acids in the range of 50-100% by titrimetric method of analysis or Preparation of Composition-4 30-100% by HPLC method of analysis can be obtained by 65 purification of the Boswellia serrata gum resin or Boswellia Composition-4 was prepared by mixing unit doses of the serrata extracts or by dilution of higher grade material. following components; one part of Boswellia carterii low US 8,551.496 B2 21 22 polar gum resin extract (BcLPRE) (1 g) and two parts of polar gum resin extract (BcLPRE) (1 g) and one part of Boswellia carterii extract standardized to 85% total Boswell- Boswellia carterii extract standardized to 65% Boswellic lic acids (BCE 85%) (2 g). acids (BCE 65%) (1 g). Example 9 5 Example 15 Preparation of Composition-5 Composition-11 Composition-5 was prepared by mixing unit doses of the Composition-11 was prepared by mixing unit doses of the following components; two parts of Boswellia serrata low 10 following components; two parts of Boswellia serrata low polar gum resin extract (BSLPRE) (2 g) and one part of polar gum resin extract (BSLPRE) (2 g), two parts of Boswellia Serrata extract standardized to 85% Boswellic Boswellia Serrata extract standardized to 85% Boswellic acids (BSE 85%) (1 g). acids (BSE 85%) (2 g) and one part of white dextrin (1 g). Example 10 15 Example 16 Preparation of Composition-6 Composition-12 Composition-12 was prepared by mixing unit doses of the f E. N piphy g y doses sts following components; two parts of Boswellia carterii low ollowing components; two parts of Boswellia carterii low polar gum resin extract (BcLPRE) (2 g), two parts of polar gum resin extract (BcLPRE) (2 g) ad one part of Boswellia carterii extract standardized to 85% Boswellic Boswellia carterii extract standardized to 85% Boswellic acids (BCE 85%) (2 g) and one part of white dextrin (1 g). acids (BCE 85%) (1 g). Example 17 Example 11 25 Composition-13 Preparation of Composition-7A Composition-13 was prepared by mixing unit doses of the Composition-7A was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; one part of Boswellia serrata low polar gum resin extract (BSLPRE) (2 g), two parts of polar gum resin extract (BSLPRE) (1 g) and two parts of Boswellia serrata extract enriched with 95% of 3-O-acetyl Boswellia Serrata extract standardized to 65% Boswellic 11-keto-B-Boswellic acid (4 g). acids ((BSE 65%)6) (2 g)g). Example 18 Preparation of Composition-7B 35 Composition-14 Composition-7B was prepared by mixing unit doses of the following components; one part of Boswellia serrata low Composition-14 was prepared by mixing unit doses of the polar gum resin extract (BSLPRE) (1 g) and two parts of following components; one part of Boswellia carterii low Boswellia carterii extract standardized to 65% Boswellic pla gum resin extract (BcLPRE) (2 g). two parts of a Boswellia carterii extract enriched with 95% of 3-O-acetyl acids (BCE 65%) (2 g). 11-keto-B-Boswellic acid (4 g). Example 12 Example 19 Preparation of Composition-8 Composition-15 45 Composition-8 was prepared by mixing unit doses of the Composition-15 was prepared by mixing unit doses of the following components; one part of Boswellia carterii low following components; one part of Boswellia serrata low polar gum resin extract (BcLPRE) (1 g) and two parts of polar gum resin extract (BSLPRE) (2 g), two parts of Boswellia carterii extract standardized to 65% Boswellic Boswellia serrata extract enriched with 40% of 3-O-acetyl acids (BCE 65%) (2 g). 50 B-Boswellic acid (4 g). Example 13 Example 20 Preparation of Composition-9 Composition-16 55 Composition-9 was prepared by mixing unit doses of the Composition-16 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; one part of Boswellia carterii low polar gum resin extract (BSLPRE) (1 g) and one part of polar gum resin extract (BcLPRE) (2 g), two parts of Boswellia Serrata extract standardized to 65% Boswellic Boswellia carterii extract enriched with 40% of 3-O-acetyl acids (BSE 65%) (1 g). 60 B-Boswellic acid (4 g). Example 14 Example 21 Preparation of Composition-10 Preparation of Composition-17 65 Composition-10 was prepared by mixing unit doses of the Composition-17 was prepared by mixing unit doses of the following components; one part of Boswellia carterii low following components; one part of Boswellia carterii low US 8,551.496 B2 23 24 polar gum resin extract (BcLPRE) (1 g) and one part of polar gum resin extract (BSLPRE) (1 g), two parts of Boswellia Serrata extract standardized to 85% total Boswell Boswellia carterii extract standardized to 85% total Boswell lic acids (BSE 85%) (1 g). lic acids (BCE 85%) (2 g) and one part of white dextrin (1 g). Example 22 Example 28 Preparation of Composition-18 Preparation of Curcuma longa Extract 20-99% Curcuminoids (CLE 20-99%) or Curcuma aromatica Composition-18 was prepared by mixing unit doses of the Extract 20-99% Curcuminoids (CAE 20-99%) following components; one part of Boswellia carterii low polar gum resin extract (BcLPRE) (1 g) and two parts of 10 The Curcuma extract standardized to 95% curcuminoids is Boswellia Serrata extract standardized to 85% total Boswell an enriched product obtained from Curcuma species and it lic acids (BSE 85%) (2 g). comprises curcumin, demethoxycurcumin and bis demethoxycurcumin. These and low assay curcuna extracts Example 23 can be procured from the commercially available extracts or 15 can be produced using one or more of the following proce Preparation of Composition-19 dures. Extraction of Curcuna longa rhizome with methanol followed by evaporation of the solvent and washing the resi due with hexane gives 20-25% total Curcuminoids by HPLC. Composition-19 was prepared by mixing unit doses of the Precipitation of this 20-25% total Curcuminoids product in following components; one part of Boswellia carterii low n-butanol/hexane mixture gives a residue, which on vacuum polar gum resin extract (BcLPRE) (1 g), two parts of drying gives 90-95% total Curcuminoids by HPLC. Option Boswellia Serrata extract standardized to 85% total Boswell ally, extraction of Curcuna longa rhizome with acetone or lic acids (BSE 85%) (2 g) and one part of white dextrin (1 g). ethyl acetate followed by evaporation of the solvent gives Curcuma longa extract comprising 50-60% total Curcumi Example 24 noids. Alternately the low grade extracts can be purified to 25 required concentration of total Curcuminoids using, precipi Preparation of Composition-20 tations, washings, chromatography techniques, resin purifi cations or combinations thereof. Similar processes or tech Composition-20 was prepared by mixing unit doses of the niques can also be applied to other Curcuma species following components; two parts of Boswellia carterii low including but not limited to Curcuma aromatica, Curcuna polar gum resin extract (BcLPRE) (2 g) and one part of 30 Zedoaria and Curcuma amada to obtain required concentra Boswellia Serrata extract standardized to 85% Boswellic tion of total Curcuminoids. acids (BSE 85%) (1 g). Example 29 Example 25 35 Preparation of Composition-24 Preparation of Composition-21 Composition-24 was prepared by mixing unit doses of the Composition-21 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; one part of Boswellia serrata low polar gum resin extract (BSLPRE) (1 g) and one part of polar gum resin extract (BSLPRE) (1 g) and one part of 40 Curcuma longa extract standardized to 95% total Curcumi Boswellia carterii extract standardized to 85% total Boswell noids (CLE 95%) (1 g). lic acids (BCE 85%) (1 g). Example 30 Example 26 45 Preparation of Composition-25 Preparation of Composition-22A Composition-25 was prepared by mixing unit doses of the following components; one part of Boswellia carterii low Composition-22A was prepared by mixing unit doses of polar gum resin extract (BcLPRE) (1 g) and one part of the following components; one part of Boswellia serrata low Curcuma longa extract standardized to 95% total Curcumi polar gum resin extract (BSLPRE) (1 g) and two parts of 50 noids (CLE 95%) (1 g). Boswellia carterii extract standardized to 85% total Boswell lic acids (BCE 85%) (2 g). Example 31 Preparation of Composition-22B Preparation of Composition-26 55 Composition-22B was prepared by mixing unit doses of Composition-26 was prepared by mixing unit doses of the the following components; two parts of Boswellia serrata low following components; one part of Boswellia serrata low polar gum resin extract (BSLPRE) (2 g) and one part of polar gum resin extract (BSLPRE) (1 g) and two parts of Boswellia carterii extract standardized to 85% Boswellic Curcuma longa extract standardized to 95% total Curcumi acids (BCE 85%) (1 g). 60 noids (CLE 95%) (2 g). Example 27 Example 32 Preparation of Composition-23 Preparation of Composition-27 65 Composition-23 was prepared by mixing unit doses of the Composition-27 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; one part of Boswellia carterii low US 8,551.496 B2 25 26 polar gum resin extract (BcLPRE) (1 g) and two parts of polar gum resin extract (BSLPRE) (1 g) and two parts of Curcuma longa extract standardized to 95% total Curcumi Curcuma aromatica extract standardized to 95% total Cur noids (CLE 95%) (2 g). cuminoids (CAE 95%) (2 g). Example 33 Example 40 Preparation of Composition-28 Preparation of Composition-35 Composition-28 was prepared by mixing unit doses of the Composition-35 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; one part of Boswellia carterii low polar gum resin extract (BSLPRE) (1 g), two parts of Cur 10 polar gum resin extract (BcLPRE) (1 g) and two parts of cuma longa extract standardized to 95% total Curcuminoids Curcuma aromatica extract standardized to 95% total Cur (CLE 95%) (2 g) and one part of white dextrin (1 g). cuminoids (CAE 95%) (2 g). Example 34 Example 41 15 Preparation of Composition-29 Preparation of Composition-36 Composition-29 was prepared by mixing unit doses of the Composition-36 was prepared by mixing unit doses of the following components; one part of Boswellia carterii low following components; one part of Boswellia serrata low polar gum resin extract (BcLPRE) (1 g), two parts of Cur polar gum resin extract (BSLPRE) (1 g), two parts of Cur cuma longa extract standardized to 95% total Curcuminoids cuma aromatica extract standardized to 95% total Curcumi (CLE 95%) (2 g) and one part of white dextrin (1 g). noids (CAE 95%) (2 g) and one part of white dextrin (1 g). Example 35 Example 42 Preparation of Composition-30 25 Preparation of Composition-37 Composition-30 was prepared by mixing unit doses of the Composition-37 was prepared by mixing unit doses of the following components; two parts of Boswellia serrata low following components; one part of Boswellia carterii low polar gum resin extract (BSLPRE) (2 g) and one part of polar gum resin extract (BcLPRE) (1 g), two parts of Cur Curcuma longa extract standardized to 95% total Curcumi cuma aromatica extract standardized to 95% total Curcumi noids (CLE 95%) (1 g). noids (CAE 95%) (2 g) and one part of white dextrin (1 g). Example 36 Example 43

Preparation of Composition-31 35 Preparation of Composition-38 Composition-31 was prepared by mixing unit doses of the Composition-38 was prepared by mixing unit doses of the following components; two parts of Boswellia carterii low following components; two parts of Boswellia serrata low polar gum resin extract (BcLPRE) (2 g) and one part of polar gum resin extract (BSLPRE) (2 g) and one part of Curcuma longa extract standardized to 95% total Curcumi 40 Curcuma aromatica extract standardized to 95% total Cur noids (CLE 95%) (1 g). cuminoids (CAE 95%) (1 g). Example 37 Example 44 Preparation of Composition-32 Preparation of Composition-39 45 Composition-32 was prepared by mixing unit doses of the Composition-39 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; two parts of Boswellia carterii low polar gum resin extract (BSLPRE) (1 g) and one part of polar gum resin extract (BcLPRE) (2 g) and one part of Curcuma aromatica extract standardized to 95% total Cur Curcuma aromatica extract standardized to 95% total Cur cuminoids (CAE 95%) (1 g). 50 cuminoids (CAE 95%) (1 g). Example 38 Example 45 Preparation of Composition-33 Preparation of Composition-40 55 Composition-33 was prepared by mixing unit doses of the Composition-40 was prepared by mixing unit doses of the following components; one part of Boswellia carterii low following components; one part of Boswellia serrata low polar gum resin extract (BcLPRE) (1 g) and one part of polar gum resin extract (BSLPRE) (1 g) and one part of Curcuma aromatica extract standardized to 95% total Cur Curcuma longa extract standardized to 20% total Curcumi cuminoids (CAE 95%) (1 g). 60 noids (CLE 2.0%) (1 g). Example 39 Example 46 Preparation of Composition-34 Preparation of Composition-41 65 Composition-34 was prepared by mixing unit doses of the Composition-41 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; one part of Boswellia carterii low US 8,551.496 B2 27 28 polar gum resin extract (BcLPRE) (1 g) and one part of polar gum resin extract (BSLPRE) (1 g) and one part of Curcuma longa extract standardized to 20% total Curcumi Curcuma aromatica extract standardized to 20% total Cur noids (CLE 2.0%) (1 g). cuminoids (CAE 20%) (1 g). Example 47 5 Example 54 Preparation of Composition-42 Preparation of Composition-49 Composition-42 was prepared by mixing unit doses of the Composition-49 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; one part of Boswellia carterii low polar gum resin extract (BSLPRE) (1 g) and two parts of 10 polar gum resin extract (BcLPRE) (1 g) and one part of Curcuma longa extract standardized to 20% total Curcumi Curcuma aromatica extract standardized to 20% total Cur noids (CLE 2.0%) (2 g). cuminoids (CAE 20%) (1 g). Example 48 Example 55 15 Preparation of Composition-43 Preparation of Composition-50 Composition-43 was prepared by mixing unit doses of the Composition-50 was prepared by mixing unit doses of the following components; one part of Boswellia carterii low following components; one part of Boswellia serrata low polar gum resin extract (BcLPRE) (1 g) and two parts of 20 polar gum resin extract (BSLPRE) (1 g) and two parts of Curcuma longa extract standardized to 20% total Curcumi Curcuma aromatica extract standardized to 20% total Cur noids (CLE 2.0%) (2 g). cuminoids (CAE 20%) (2 g). Example 49 Example 56 Preparation of Composition-44 25 Preparation of Composition-51 Composition-44 was prepared by mixing unit doses of the Composition-51 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; one part of Boswellia carterii low polar gum resin extract (BSLPRE) (1 g); two parts of Cur polar gum resin extract (BcLPRE) (1 g) and two parts of cuma longa extract standardized to 20% total Curcuminoids Curcuma aromatica extract standardized to 20% total Cur (CLE 20%) (2 g) and one part of white dextrin (1 g). cuminoids (CAE 20%) (2 g). Example 50 Example 57 Preparation of Composition-45 35 Preparation of Composition-52 Composition-45 was prepared by mixing unit doses of the Composition-52 was prepared by mixing unit doses of the following components; one part of Boswellia carterii low following components; one part of Boswellia serrata low polar gum resin extract (BcLPRE) (1 g), two parts of Cur polar gum resin extract (BSLPRE) (1 g), two parts of Cur cuma longa extract standardized to 20% total Curcuminoids 40 cuma aromatica extract standardized to 20% total Curcumi (CLE 20%) (2 g) and one part of white dextrin (1 g). noids (CAE 20%) (2 g) and one part of white dextrin (1 g). Example 51 Example 58 Preparation of Composition-46 45 Preparation of Composition-53 Composition-46 was prepared by mixing unit doses of the Composition-53 was prepared by mixing unit doses of the following components; two parts of Boswellia serrata low following components; one part of Boswellia carterii low polar gum resin extract (BSLPRE) (2 g) and one part of polar gum resin extract (BcLPRE) (1 g), two parts of Cur Curcuma longa extract standardized to 20% total Curcumi cuma aromatica extract standardized to 20% total Curcumi noids (CLE 2.0%) (1 g). 50 noids (CAE 20%) (2 g) and one part of white dextrin (1 g). Example 52 Example 59 Preparation of Composition-47 Preparation of Composition-54 55 Composition-47 was prepared by mixing unit doses of the Composition-54 was prepared by mixing unit doses of the following components; two parts of Boswellia carterii low following components; two parts of Boswellia serrata low polar gum resin extract (BcLPRE) (2 g) and one part of polar gum resin extract (BSLPRE) (2 g) and one part of Curcuma longa extract standardized to 20% total Curcumi Curcuma aromatica extract standardized to 20% total Cur noids (CLE 2.0%) (1 g). 60 cuminoids (CAE 20%) (1 g). Example 53 Example 60 Preparation of Composition-48 Preparation of Composition-55 65 Composition-48 was prepared by mixing unit doses of the Composition-55 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low following components; two parts of Boswellia carterii low US 8,551.496 B2 29 30 polar gum resin extract (BcLPRE) (2 g) and one part of 65%, composition-3A, composition-4, composition-18 and Curcuma aromatica extract standardized to 20% total Cur composition-7A was measured by incubating various con cuminoids (CAE 20%) (1 g). centrations of test substances two minutes before the addition of linoleic acid. All assays were performed three times. Per Example 61 centage inhibition was calculated by comparing slope of the curve obtained for test substances with that of the control. The Preparation of Composition-56 percentage inhibitions of BsLPRE, BcLPRE, BSE85%, BCE 85%, BSE 65%, composition-3A, composition-4, composi Composition-56 was prepared by mixing unit doses of the tion-18 and composition-7A are summarized in Table 2 and following components; one part of Boswellia serrata low 10 depicted in the FIG. 3. polar gum resin extract (BSLPRE) (1 g) and two parts of Withania Sonnifera methanol extract (2 g). TABLE 2 Example 62 5-Lipoxygenase inhibitory activity 15 5-LOX inhibition Preparation of Composition-57 S. No Test substance at 10 g/ml

1 BSLPRE 15.13 Composition-57 was prepared by mixing unit doses of the 2 BCLPRE 14.36 following components; one part of Boswellia serrata low 3 BSE 85% 21.04 polar gum resin extract (BSLPRE) (1 g) and two parts of 4 BCE 85% 1926 Garcinia mangostana methanol extract (2 g). 5 BSE 65% 17.68 6 Composition-3A 27.12 7 Composition-4 2S.23 Example 63 8 Composition-18 24.95 9 Composition-7A 23.83 Preparation of Composition-58 25 Composition-58 was prepared by mixing unit doses of the following components; one part of Boswellia serrata low Example 67 polar gum resin extract (BSLPRE) (1 g) and two parts of Annona squamosa ethanol extract (2 g). 30 The In Vivo Anti-Inflammatory Activity of Boswellia Low Polar Gum Resin Extract (BsLPRE and Example 64 BcLPRE), a Few Boswellia Extracts, Curcuma Extracts and their Compositions Preparation of Composition-59 35 The anti-inflammatory efficacy of BsLPRE, BcLPRE, Composition-59 was prepared by mixing unit doses of the BSE 85%, BCE 85%, BSE 65%, CLE 20%, CLE 95%, CAE following components; one part of Boswellia serrata low 20%, CAE 95%, composition-3A, composition-4, composi polar gum resin extract (BSLPRE) (1 g) and two parts of tion-18, composition-7A, composition-42, composition-26, Sphaeranthus indicus ethyl acetate extract (2 g). composition-51 and composition-35 were evaluated in an in 40 vivo study in Freund's Complete Adjuvant induced arthritis Example 65 model of Sprague Dawley rats. Prednisolone was used as a positive control. The rats of either sex were randomly selected Preparation of Composition-60 and divided into nineteen groups containing six animals per group. The treatment group rats were Supplemented daily Composition-60 was prepared by mixing unit doses of the 45 following components; one part of Boswellia serrata low with 200 mg/kg body weight of one of BsLPRE, BcLPRE, BSE 85%, BCE 85%, BSE 65%, CLE 20%, CLE 95%, CAE polar gum resin extract (BSLPRE) (1 g) and two parts of 20%, CAE 95%, composition-3A, composition-4, composi Bacopa monniera 90% methanol/water extract (2 g). tion-18, composition-7A, composition-42, composition-26, Example 66 50 composition-51 and composition-35 for 14 days. The positive control group was supplemented daily with Prednisolone at Evaluation of 5-Lipoxygenase Inhibitory Activity of 10 mg/kg body weight. All supplements were diluted in 10 BsLPRE, BcLPRE, BSE 85%, BCE 85%, BSE 65%, mL of 1% CMC for administration. The animals of control Composition-3A, Composition-4, Composition-18 group received same volume of 1% CMC. At the 14th day, and Composition-7A 55 Freund's Complete Adjuvant (FCA) was injected subcutane ously in the sub-plantar region of the left hind paw of each 5-Lipoxygenase enzyme inhibitory activity was measured animal. The experiment was terminated on 28" day. Blood using the method of Schewe et al. (Adv Enzymol, Vol 58, samples were collected from each animal at regular intervals 191-272, 1986), modified by Reddanna et. al., (Methods of and paw Volumes were measured by Plethysmography equip Enzymology, Vol 187, 268-277, 1990). The assay mixture 60 ment on the day of FCA injection and after 13 days of FCA contained 80 uMlinoleic acid and sufficient amount of potato inoculation. The difference in volume of paw edema is con 5-lipoxygenase in 50 mM phosphate buffer (pH 6.3). The sidered as the inflammatory response. The in vivo anti-in reaction was initiated by the addition of enzyme buffer mix to flammatory response of BsLPRE, BcLPRE, BSE 85%, BCE linoleic acid and the enzyme activity was monitored as the 85%, BSE 65%, CLE 20%, CLE 95%, CAE 20%, CAE 95%, increase in absorbance at 234 nm. The reaction was moni 65 composition-3A, composition-4, composition-18, composi tored for 120 sec and the inhibitory potential of the test tion-7A, composition-42, composition-26, composition-51, substances, BSLPRE, BcLPRE, BSE 85%, BCE 85%, BSE composition-35 and Prednisolone were estimated by calcu US 8,551.496 B2 31 32 lating the percentage inhibition of paw edema when com Boswellia elongata, Boswellia frereana, Boswellia nana, pared to the CMC supplemented control. Boswellia neglecta, Boswellia Ogadensis, Boswelliapirottae, The treatment groups Supplemented with 200 mg/kg body Boswellia popoviana, Boswellia rivae, Boswellia sacra and weight of Boswellia serrata low polar gum resin extract Boswellia Socotrana, and mixtures thereof. (BSLPRE) and 200 mg/kg body weight of Boswellia serrata 3. The Boswellia gum resin extract as claimed in claim 1, extract standardized to 85% total Boswellic acids (BSE85%) wherein said at least one plant in the genus Boswellia is showed 23% and 30% reduction in paw edema respectively. selected from the group consisting of Boswellia serrata, However, the treatment group Supplemented with composi Boswellia carterii, Boswellia papyrifera, and mixtures tion-3A at the same dose level showed better reduction and thereof. achieved 42% reduction in paw edema volume. The positive 10 control group supplemented with Prednisolone exhibited 4. The Boswellia gum resin extract as claimed in claim 1, 46% inhibition at 10 mg/kg dose level. Similarly, the other wherein said at least one plant in the genus Boswellia is inventive compositions composition-4, composition-18, selected from the group consisting of Boswellia serrata, and composition-7A, composition-42, composition-26, composi wherein said Boswellia gum resin extract comprises at tion-51 and composition-35 also exhibited synergistic effects 15 least three compounds selected from guiol (1), neph as summarized in FIG. 4 and Table 3 confirming the observed thenol (2), serratol (3), diterpeneX (4), lupeol (5), olean in vitro results. 12-ene-3?-ol (6), olean-12-ene-3C-ol (7), lanosta-8.24 diene-3C-ol (8) and urs-12-ene-3C.-ol (9). TABLE 3 5. A composition comprising the Boswellia gum resin extract according to claim 1, said composition further com Reduction in Paw volume activity prising at least one component selected from the group con Reduction in Paw Concentration sisting of distilled water, Saline Solution, aqueous glucose S. No Test substance edema mg/kg body weight Solution, alcohol, propylene glycol, polyethylene glycol, 1 BSLPRE 23 2OO glycerin, animal oils, vegetable oils, white soft paraffin, par 25 2 BCLPRE 19 2OO affin, wax, glucose, fructose, Sucrose, maltose, yellow dex 3 BSE 85% 30 2OO trin, white dextrin, aerosol, microcrystalline cellulose, cal 4 BCE 85% 28 2OO S BSE 65% 24 2OO cium Stearate, magnesium Stearate, Sorbitol, Stevioside, corn 6 CLE 20% 10 2OO syrup, lactose, citric acid, tartaric acid, malic acid, Succinic 7 CLE 95% 25 2OO acid, lactic acid, L-ascorbic acid, d1-alpha-tocopherol, glyc 8 CAE 20% 8 2OO 30 erin fatty ester, poly glycerin fatty ester, Sucrose fatty ester, 9 CAE 95% 23 2OO 10 Composition-3A 42 2OO sorbitan fatty ester, propylene glycol fatty ester, acacia, car 11 Composition-4 38 2OO rageenan, casein, gelatin, pectin, agar, Vitamin B group, nico 12 Composition-18 35 2OO tinamide, calcium pantothenate, amino acids, calcium salts, 13 Composition-7A 31 2OO 14 Composition-42 26 2OO 35 pigments, flavors and preservatives. 15 Composition-26 35 2OO 6. A composition comprising the Boswellia gum resin 16 Composition-51 21 2OO extract as claimed in claim 1, said composition further com 17 Composition-35 33 2OO prising at least one component selected from the group con 18 Prednisolone 46 10 sisting of a biologically active ingredient, an excipient, a 40 diluent, a carrier, an additive, and mixtures thereof. It will be appreciated by those of ordinary skilled in the art 7. The composition as claimed in claim 6, wherein said that changes could be made to the embodiments described biologically active ingredient comprises at least one compo above without departing from the broad inventive concept nent derived from a plant, an animal, a microorganism, or a thereof. It is understood, therefore, that this invention is not mixture thereof. limited to the particular embodiments or examples disclosed, 45 8. The composition as claimed in claim 6, wherein said but is intended to cover modifications within the embodi biologically active ingredient comprises one or more ingre ments and scope of the present invention. dients selected from the group consisting of herbal ingredi What is claimed is: ents, antioxidants, vitamins, minerals, amino acids, fatty 1. A Boswellia gum resin extract derived from a gum resin acids, essential oils, fish oils, enzymes and probiotics. of at least one plant in the genus Boswellia, 50 9. The composition as claimed in claim 6, wherein the wherein said Boswellia gum resin extract is obtained by: composition comprises said biologically active ingredient, a) extracting the Boswellia gum resin with a solvent to said biologically active ingredient comprising at least one obtain a Boswellia extract; component selected from the group consisting of: b) partitioning the Boswellia extract between an aqueous i.at least one boswellic acid or a salt thereof alkali solution and a water-immiscible organic solvent; 55 ii. a boswellic acid-containing extract of at least one plant c) evaporating the water-immiscible organic solvent to Selected from the group consisting of Boswellia serrata, obtain a water immiscible organic solvent extract of Boswellia carterii, Boswellia papyrifera, and mixtures Boswellia; and thereof; d) at least partially evaporating volatile components from iii. at least one curcuminoid or a salt thereof, and the water-immiscible organic solvent extract of 60 iv. a curcuminoid-containing extract of a plant from the Boswellia under high vacuum at an elevated tempera genus Curcuna. ture. 10. The composition as claimed in claim 9, wherein said 2. The Boswellia gum resin extract as claimed in claim 1, biologically active ingredient is said boswellic acid-contain wherein said at least one plant in the genus Boswellia is ing extract, said boswellic acid-containing extract comprising selected from the group consisting of Boswellia serrata, 65 between about 30% and about 100% total boswellic acids. Boswellia carterii, Boswellia papyrifera, Boswellia ameero, 11. The composition as claimed in claim 10, wherein said Boswellia bullata, Boswellia dalzielii, Boswellia dioScorides, composition comprises from about 5% to about 95% by US 8,551.496 B2 33 34 weight of said boswellic acid-containing extract, and from iii. at least one curcuminoid or a salt thereof, and about 5% to about 95% by weight of said Boswellia gum resin iv. a curcuminoid-containing extract of a plant from the eXtract. genus Curcuma, 12. The composition as claimed in claim 10, wherein said said biological marker being selected from the group con composition comprises from about 20% to about 80% by sisting of 5-lipoxygenase (5-LOX), 5-Lipoxygenase weight of said boswellic acid-containing extract, and from activating protein (FLAP), Macrophage/Adipocyte about 20% to about 80% by weight of said Boswellia gum Fatty acid binding protein (aP2), IFN-y, IL-4, ICAM, resin extract. VCAM, MMPs, TNFC, NFKB, IL-1 B, and combina 13. The composition as claimed in claim 10, wherein said tions thereof. composition comprises from about 33% to about 67% by 10 22. A process for preparation of a composition comprising weight of said boswellic acid-containing extract, and from about 33% to about 67% by weight of said Boswellia gum Boswellia gum resin extract, wherein the process comprises: resin extract. a) extracting the Boswellia gum resin with a solvent to 14. The composition as claimed in claim 9, wherein said obtain a Boswellia extract; biologically active ingredient is said curcuminoid-containing 15 b) partitioning the Boswellia extract between an aqueous extract, said curcuminoid-containing extract comprising alkali solution and a water-immiscible organic solvent; between about 20% and 99% of said at least one curcuminoid. c) evaporating the water-immiscible organic solvent to 15. The composition as claimed in claim 14, wherein said obtain a water-immiscible organic solvent extract of curcuminoid-containing extract is an extract of a plant Boswellia; and selected from the group consisting of Curcuma longa, Cur d) at least partially evaporating volatile components from cuma aromatica, and mixtures thereof. the water-immiscible organic solvent extract of 16. The composition as claimed in claim 15, wherein said Boswellia under high vacuum at an elevated tempera composition comprises from about 5% to about 95% by ture. weight of said curcuminoid-containing extract, and from 23. The process as claimed in claim 22, wherein the water about 5% to about 95% by weight of said Boswellia gum resin 25 immiscible organic solvent is selected from the group con eXtract. sisting of 1,2-dichloroethane, hexane, dichloromethane, 17. The composition as claimed in claim 15, wherein said chloroform, ethyl acetate, n-butanol, methyl iso-butyl ketone composition comprises from about 20% to about 80% by (MIBK), and mixtures thereof. weight of said curcuminoid-containing extract, and from 24. The process as claimed in claim 22, wherein the alkali about 20% to about 80% by weight of said Boswellia gum 30 Solution is an aqueous solution of a metal hydroxide selected resin extract. from the group consisting of Group I metal hydroxide, Group 18. The composition as claimed in claim 15, wherein said composition comprises from about 33% to about 67% by II metal hydroxide, and mixtures thereof. weight of said curcuminoid-containing extract, and from 25. The process according to claim 22, further comprising: about 33% to about 67% by weight of said Boswellia gum 35 (e) obtaining a boswellic acid-containing extract of at least resin extract. one plant selected from the group consisting of 19. A method of treating inflammation in a warm blooded Boswellia serrata, Boswellia carterii, Boswellia papy animal, comprising administering the Boswellia gum resin rifera, and mixtures thereof; extract as claimed in claim 1 to said warm blooded animal, (f) combining the Boswellia gum resin extract and the said Boswellia gum resin extract optionally being adminis 40 boswellic acid-containing extract in a desired ratio to tered in combination with at least one component selected obtain a synergistic composition; and from the group consisting of (g) optionally combining the synergistic composition with i.at least one boswellic acid or a salt thereof; at least one component selected from the group consist ii. a boswellic acid-containing extract of at least one plant ing of biologically active ingredients, excipients, dilu Selected from the group consisting of Boswellia serrata, 45 ents, carriers and additives. Boswellia carterii, Boswellia papyrifera, and mixtures 26. The process according to claim 22, further comprising: thereof; (e) obtaining a curcuminoid-containing extract of at least iii. at least one curcuminoid or a salt thereof, and one plant from the genus Curcuma, iv. a curcuminoid-containing extract of a plant from the (f) combining the Boswellia gum resin extract and the genus Curcuna. 50 curcuminoid-containing extract in a desired ratio to 20. The method as claimed in claim 19, wherein said obtain a synergistic composition; and administering comprises administering the Boswellia gum (g) optionally combining the synergistic composition with resin extract to said warm blooded animal by an oral, dermal, at least one component selected from the group consist intravenous, Subcutaneous, intra-peritoneal, rectal or intra ing of biologically active ingredients, excipients, dilu muscular route. 55 ents, carriers and additives. 21. A method of treating a condition associated with at least 27. The process for preparation of a composition compris one biological marker in a warm blooded animal, comprising ing Boswellia gum resin extract according to claim 22, administering the Boswellia gum resin extract as claimed in wherein: claim 1 to said warm blooded animal in need thereof, said said extracting comprises extracting the Boswellia gum Boswellia gum resin extract optionally being administered in 60 resin with an alcoholic solvent or a hydroalcoholic sol combination with at least one component selected from the vent to produce an alcoholic extract; and group consisting of said partitioning comprises partitioning the alcoholic i.at least one boswellic acid or a salt thereof; extract between said aqueous alkali solution and said ii. a boswellic acid-containing extract of at least one plant water-immiscible organic solvent. Selected from the group consisting of Boswellia serrata, 65 28. The process for preparation of a composition compris Boswellia carterii, Boswellia papyrifera, and mixtures ing Boswellia gum resin extract according to claim 22, thereof; wherein: US 8,551.496 B2 35 36 said extracting comprises extracting the Boswellia gum resin with a water-immiscible organic solvent to pro duce an water-immiscible organic solvent extract solu tion; and said partitioning comprises extracting the water-immis- 5 cible organic solvent extract solution with said aqueous alkali solution.