Bacillus coagulans MTCC 5856 to confer protection to the skin fibroblasts against UV induced cell damage and apoptosis, oxidative stress and inflammation.
A61K 8/99 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
A61Q 17/04 - Topical preparations for affording protection against sunlight or other radiationTopical sun tanning preparations
Terminalia arjuna extract standardized to contain 3% w/w arjunoglucosides for use a prostaglandin transporter inhibitor. The invention also discloses the use of the aforementioned composition in the therapeutic management of hypertension and cardiovascular complications.
A61K 31/122 - Ketones having the oxygen atom directly attached to a ring, e.g. quinones, vitamin K1, anthralin
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
Bacillus coagulans strain FF-7 (MTCC 25235) and the process of isolation and characterization of the bacteria. The invention also discloses the biological applications/therapeutic use of fructophilic lactic acid producing bacteria in increased utilization of fructose from food stuff and in the managing disorders related to high fructose intake.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
A61K 35/742 - Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
4.
Composition for therapeutic management of hypomelanotic skin conditions
Piper nigrum extract standardized to contain not less than 95% w/w piperine extract for use in enhancing melanogenesis in mammalian cells. The invention also discloses the use of above mentioned composition in the therapeutic management of hypomelanotic skin conditions and in reducing the progression of depigmentation of skin in vitiligo in mammalian skin.
A61K 36/00 - Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
A61K 36/67 - Piperaceae (Pepper family), e.g. Jamaican pepper or kava
A61K 36/71 - Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
The present invention discloses a composition for the therapeutic management of male sexual dysfunction and related disorders. Specifically, the invention discloses a composition comprising 60-65% w/w Withania somnifera extract, 12-18% w/w Mucana pruriens extract, 5- 10% w/w Coleus forskolii extract, 12-18% w/w Kaempferia parviflora extract, 0.1 - 2% w/w Piper nigrum extract, for use as an aphrodisiac.
Bacillus coagulans and water soluble prebiotic fibers that have been subjected to treatments under extreme stress, temperature and pressure conditions like brewing or aeration wherein the spore viability is maintained post said treatments.
Curcuma longa) and compositions comprising said bioactive components. Further, the present invention also elucidates the potent anti-inflammatory activity of said bioactive compositions and therapeutic applications thereof in rheumatoid arthritis.
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
Disclosed is a method for enhancing the activity of telomerase using a composition containing ecdysterone. The invention also discloses the use of a composition containing ecdysterone and/or an extract containing ecdysterone, isolated from a plant source in preventing/delaying cell aging in mammals by increasing the activity of telomerase.
A61K 31/56 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids
A61K 31/568 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. oestrane, oestradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstane, testosterone
A61Q 7/00 - Preparations for affecting hair growth
The present invention discloses a composition comprising heat inactivated spores and/or comprising heat inactivated vegetative cells of probiotic bacteria Bacillus coagulans, and a process for preparing the same. The invention also discloses a method of modulating immune function in mammals by activating macrophages, using a composition comprising Bacillus coagulans in the form of live or heat inactivated spore and/or vegetative cells.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
12.
MODULATION OF IMMUNE FUNCTION BY BACILLUS COAGULANS
The present invention discloses a composition comprising heat inactivated spores and/or comprising heat inactivated vegetative cells of probiotic bacteria Bacillus coagulans, and a process for preparing the same. The invention also discloses a method of modulating immune function in mammals by activating macrophages, using a composition comprising Bacillus coagulans in the form of live or heat inactivated spore and/or vegetative cells.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
A61K 35/742 - Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
Coleus forskohlii standardized to contain not less than 10% w/w forskolin for the therapeutic management of diet induced obesity and weight gain and related conditions like liver dysfunction, NASH, NAFLD, liver cirrhosis, hypercholesterolemia, hyperlipidemia, kidney dysfunction by bringing about a reduction in body weight, increasing lean body mass and by normalizing the levels of liver enzymes, kidney markers and circulating lipids.
The present invention discloses a synergistic composition comprising 3-O-ethyl-ascorbic acid and tetrahydrocurcuminoids for use as a skin lightening agent. The invention also discloses a method of inhibiting melanin biosynthesis and tyrosinase activity in mammalian skin cells using a composition comprising 3-O-ethyl-ascorbic acid and tetrahydrocurcuminoids.
The invention pertains to a composition comprising Curcuminoids and Garcinol for hepatoprotection. Specifically, the invention discloses a composition comprising 95% Curcuminoids and 20% Garcinol for the therapeutic management of Non-alcoholic fatty liver disease (NAFLD) and associated conditions like steatosis, Non-alcoholic steatoheapatitis (NASH), fibrosis and cirrhosis of the liver.
The invention pertains to a composition comprising Curcuminoids and Garcinol for hepatoprotection. Specifically, the invention discloses a composition comprising 95% Curcuminoids and 20% Garcinol for the therapeutic management of Non-alcoholic fatty liver disease (NAFLD) and associated conditions like steatosis, Non-alcoholic steatoheapatitis (NASH), fibrosis and cirrhosis of the liver.
A23L 33/105 - Plant extracts, their artificial duplicates or their derivatives
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
18.
Process for the preparation of enantiopure 3-amino tetrahydrofuran and its salts
C07D 307/22 - Nitrogen atoms not forming part of a nitro radical
C07C 271/16 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
C07C 233/69 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of an acyclic saturated carbon skeleton
C07C 233/83 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of an acyclic saturated carbon skeleton
Disclosed is a novel, simple, scalable and environment friendly process for the synthesis of Oroxylin A from Baicalin. Baicalin is esterified to obtain a methyl ester which is further selectively methylated to provide Oroxylin A glucuronide methyl ester which on de-glycosylation results in the formation of Oroxylin A.
C07D 311/30 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
20.
COMPOSITIONS FOR THE MANAGEMENT OF HYPERGLYCEMIA AND RELATED CONDITIONS
Disclosed is a method for therapeutic management of hyperglycemia in mammals using compositions containing thymohydroquinone. More specifically, the invention discloses compositions containing thymohydroquinone for inhibiting the activity of the enzyme a-glucosidase and increasing the cellular uptake of glucose by mammalian cells. The anti-oxidant, anti-inflammatory and anti-glycation effects of thymohydroquinone are also disclosed herein.
Disclosed are compositions enriched with thymohydroquinone, further comprising of thymoquinone, hederagenm and/or a-hederin formulated by blending the active molecules isolated from the seeds of Nigella sativa. Also disclosed are novel processes for the isolation of bioactive components thymohydroquinone, thymoquinone from the seeds of Nigella sativa. A process for the isolation a-hederin and hederagenin from the spent material of Nigella sativa is also disclosed herein.
A61K 31/122 - Ketones having the oxygen atom directly attached to a ring, e.g. quinones, vitamin K1, anthralin
A61K 31/56 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 36/71 - Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
22.
Compositions containing thymohydroquinone and their method of preparation
A61K 36/71 - Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 31/191 - Acyclic acids having two or more hydroxy groups, e.g. gluconic acid
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
Disclosed is a method for therapeutic management of hyperglycemia in mammals using compositions containing thymohydroquinone. More specifically, the invention discloses compositions containing thymohydroquinone for inhibiting the activity of the enzyme α-glucosidase and increasing the cellular uptake of glucose by mammalian cells. The anti-oxidant, anti-inflammatory and anti-glycation effects of thymohydroquinone are also disclosed herein.
A61K 36/71 - Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 31/191 - Acyclic acids having two or more hydroxy groups, e.g. gluconic acid
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 36/00 - Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
A23L 33/105 - Plant extracts, their artificial duplicates or their derivatives
The present invention discloses the microbial anti-adhesion effect of probiotic bacteria Bacillus coagulans MTCC 5856. More specifically the invention discloses the ability of a composition containing probiotic bacteria Bacillus coagulans MTCC 5856 in inhibiting the adhesion of harmful pathogenic microbes to the skin and mucosal surfaces thereby preventing the occurrence of an infection. Compositions containing probiotic bacteria Bacillus coagulans MTCC 5856 along with plant/fruit extracts for use as an anti-adhesion agent are also disclosed.
The present disclosure provides oleanoyl tripeptide to prevent skin aging. More specifically the invention discloses the anti-collagenase, anti-elastase, enhancement of TGF-β secretion in fibroblasts, UV protection, oxidative stress protection, and other properties of the oleanoyl-KVK tripeptide which aids in preventing skin aging.
Disclosed are the anti-poliution effects of probiotic bacteria Bacilluscoagulans MTCC 5856. More specifically the invention discloses the use of probiotic bacteria Bacilluscoagulans MTCC 5856 in protecting mammalian skin against the harmful effects of UV and different environmental pollutants. The use of Bacillus coagulans MTCC 5856, as an antioxidant, skin rejuvenating and cleansing agent is also disclosed.
A61K 8/99 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
The present invention relates to a process for the isolation of bioactive components from spent turmeric (Curcuma longa) and compositions comprising said bioactive components. Further, the present invention also elucidates the potent anti-inflammatory activity of said bioactive compositions and therapeutic applications thereof in rheumatoid arthritis.
A61K 31/715 - Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkagesDerivatives thereof, e.g. ethers, esters
A61K 31/718 - Starch or degraded starch, e.g. amylose, amylopectin
A61K 36/9066 - Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
C07C 35/44 - Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with a hydroxy group on a condensed ring system having more than three rings
C07D 311/60 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4 with aryl radicals attached in position 2
C07H 15/24 - Condensed ring systems having three or more rings
Disclosed is a novel process for the isolation of bioactive compounds from Terminalia arjuna. More specifically, the invention discloses a process for isolation and enrichment of bioactive compounds Arjunic acid, Arjunolic acid, Arjungenin, Arjunetin, Arjunoglucoside-I, Arjunoglucoside-II, and Catechin from the bark of Terminalia arjuna. The invention also discloses a composition standardized to contain 3% arjunoglucosides isolated from the bark of Terminalia arjuna.
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
A61K 31/575 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
Disclosed are the uses of compositions containing not less than 10% w/w of Oroxylin A, not less than 10% w/w of Baicalein and not less than 2% w/w of Chrysin in inhibiting the activity and expression of .beta. secretase. The invention also discloses the reduction of amyloid content in PS- 70 cells using the abovementioned composition. Further, the invention mentions the use of the composition for the therapeutic management of .beta. secretase mediated disorders.
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 36/48 - Fabaceae or Leguminosae (Pea or Legume family)CaesalpiniaceaeMimosaceaePapilionaceae
Disclosed are compositions containing garcinol for the therapeutic management of obesity. More specifically, the invention relates to the use of garcinol for a) maintaining energy balance in mammalian adipose cellular systems b) management of hypercholesterolemia and c) reducing weight gain in mammals. The modification of gut microbiota and the increase of beneficial microbe, Akkermansia muciniphila by garcinol are also disclosed.
C12N 5/077 - Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
Disclosed are compositions containing not less than 10% w/w of oroxylin A, not less than 10% w/w of baicalein and not less than 2% w/w of chrysin for use in the therapeutic management of memory impairment and cognitive dysfunction. More specifically, the invention discloses the use of abovementioned compositions for the management of cognitive impairment induced by chemotherapy and hyperglycemia.
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 36/48 - Fabaceae or Leguminosae (Pea or Legume family)CaesalpiniaceaeMimosaceaePapilionaceae
Disclosed are compositions containing not less than 10% w/w of oroxylin A, not less than 10% w/w of baicalein and not less than 2% w/w of chrysin for use in the therapeutic management of memory impairment and cognitive dysfunction. More specifically, the invention discloses the use of abovementioned compositions for the management of cognitive impairment induced by chemotherapy and hyperglycemia.
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Disclosed are hair care compositions containing partially purified extracellular metabolite preparation from strains of Bacillus coagulans Specifically, the uses of compositions containing extracellular metabolite preparation from a stram of Bacillus coagulans for increasing hair growth, inhibition of 5a-reductase and proliferation of follicle dermal papilla cells and m the management of androgenic alopecia, are disclosed.
A61K 8/99 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
Disclosed is the use of partially purified extracellular metabolite isolated from Bacillus coagulans MTCC 5856 to prevent skin aging More specifically the invention discloses the anti-collagenase, anti-elastase, anti-glycation activity and enhancement of TGF-.beta., epidermal growth factor and hyaluronic acid expression in human dermal fibroblasts, of extracellular metabolites isolated from Bacillus coagulans MTCC 5856
A61K 8/99 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
C12P 1/04 - Preparation of compounds or compositions, not provided for in groups , by using microorganisms or enzymesGeneral processes for the preparation of compounds or compositions by using microorganisms or enzymes by using bacteria
Disclosed is the hypolipidemic potential of Bacillus coagulans. More specifically the invention discloses the cholesterol lowering potential of Bacillus coagulans MTCC 5856 and therapeutic/biological indications thereof.
Disclosed are the skin care applications of a composition containing the partially purified extracellular metabolite isolated from Bacillus coagulans MTCC 5856. More specifically, the invention discloses the ability of the partially purified extracellular metabolite isolated from Bacillus coagulans MTCC 5856 to confer protection to the skin fibroblasts against UV induced cell damage and apoptosis, oxidative stress and inflammation.
A61K 8/99 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
A61Q 17/04 - Topical preparations for affording protection against sunlight or other radiationTopical sun tanning preparations
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving viable microorganisms
C12Q 1/04 - Determining presence or kind of microorganismUse of selective media for testing antibiotics or bacteriocidesCompositions containing a chemical indicator therefor
Disclosed are compositions containing at least 10% w/w or above of 1-O-gaHoyl-P-D-glucose (.beta.-glucogallin) which additionally comprising of about 10% w/w to greater than 60% w/w total mucic acid gallates including mucic acid 1,4-lactone 5-O-gallate, mucic acid 2-O-gallate, mucic acid 6-Methyl ester 2-O-gallate, mucic acid 1 -Methyl ester 2-O-gallate and ellagic acid, and a probiotic bacteria Bacillus coagulans MTCC 5856, individually or in combination for inhibiting the growth and managing infections of Helicobacter pylori.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
A61K 35/742 - Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
A61K 8/99 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
Bacillus coagulans for increasing hair growth, inhibition of 5α-reductase and proliferation of follicle dermal papilla cells and in the management of androgenic alopecia, are disclosed.
A61P 17/14 - Drugs for dermatological disorders for baldness or alopecia
A61Q 7/00 - Preparations for affecting hair growth
A61K 8/99 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/44 - Oils, fats or waxes according to two or more groups of Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
Bacillus coagulans and water soluble prebiotic fibers that have been subjected to treatments under extreme stress, temperature and pressure conditions like brewing or aeration wherein the spore viability is maintained post said treatments.
Disclosed are the compositions comprising bioactive components Oroxylin A, Baicalein, Chrysin, and their glucuronides Oroxylin A-7-glucuronide, Baicalein-7-glucuronide and Chrysm-7-glucuronide, isolated from the bark of Oroxylum indicum, and the process of isolating the said bioactives.
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
49.
ENZYME COMPOSITION FOR THERAPEUTIC MANAGEMENT OF MUSCLE SORENESS
The present invention discloses a combination of digestive enzymes (Protease, Amylase, Lactase, Lipase, Cellulase) - DigeZyme® for the therapeutic management - of delayed onset muscle soreness (DOMS).
The present invention provides a method of using (E)-1-(3′, 4′-dimethoxyphenyl) butadiene to induce anti-tumorigenic effects in pancreatic carcinoma, ovarian carcinoma, prostate carcinoma, colon carcinoma, lung carcinoma, lymphoblastoma, melanoma and colorectal carcinoma. The invention also provides a method of using (E)-1-(3′, 4′-dimethoxyphenyl) butadiene to prevent cancer metastasis.
The present invention discloses the use of probiotics for therapeutic management of major depressive disorder (MDD). Specifically, the invention discloses the method of therapeutically managing MDD in mammals with Irritable bowel syndrome using probiotic strain Bacillus coagulans MTCC 5856.
The present invention discloses the use of probiotics for therapeutic management of major depressive disorder (MDD). Specifically, the invention discloses the method of therapeutically managing MDD in mammals with Irritable bowel syndrome using probiotic strain Bacillus coagulans MTCC 5856.
A61K 36/00 - Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
A23L 33/105 - Plant extracts, their artificial duplicates or their derivatives
55.
Process for enhancing the viable counts of lactic acid bacteria and useful compositions thereof
C12P 7/64 - FatsFatty oilsEster-type waxesHigher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl groupOxidised oils or fats
A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
A61K 35/742 - Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
56.
Process for enhancing the viable counts of lactic acid bacteria and useful compositions thereof
C12P 7/64 - FatsFatty oilsEster-type waxesHigher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl groupOxidised oils or fats
A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
A61K 36/45 - Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
A61K 36/47 - Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
A61K 36/48 - Fabaceae or Leguminosae (Pea or Legume family)CaesalpiniaceaeMimosaceaePapilionaceae
Disclosed is the adaptogenic activity of boswellic acids-polysaccharide compositions derived from Boswellia serrata in combination with either (i) the concentrate of the liquid endosperm of Cocos nucifera or (ii) the extract of Emblica officinalis fruit standardized to contain 10% w/w and above of 1-O-galloyl-ß-D-glucose (ß-glucogallin).
A61K 31/235 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
Disclosed is the adaptogenic activity of boswellic acids-polysaccharide compositions derived from Boswellia serrata in combination with either (i) the concentrate of the liquid endosperm of Cocos nucifera or (ii) the extract of Emblica officinalis fruit standardized to contain 10% w/w and above of 1-O-galloyl-β-D-glucose (β-glucogallin).
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
A61K 31/235 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
A61K 31/7034 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
A61K 31/715 - Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkagesDerivatives thereof, e.g. ethers, esters
A61K 36/47 - Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean)
60.
PROCESS FOR THE THERAPEUTIC MANAGEMENT OF DIARRHEA PREDOMINANT IRRITABLE BOWEL SYNDROME USING BACILLUS COAGULANS SBC37-01, MTCC 5856
The present invention discloses a process for the therapeutic management of diarrhea predominant irritable bowel syndrome in humans comprising the oral administration of Bacillus coagulans SBC37-01, MTCC 5856 (containing not less than 2 billion spores) along with standard treatment of care in a specific manner.
The present invention provides a method of using (E)-1-(3′, 4′-dimethoxyphenyl) butadiene to induce anti-tumorigenic effects in pancreatic carcinoma, ovarian carcinoma and prostate carcinoma. The invention also provides a method of using (E)-1-(3′, 4′-dimethoxyphenyl) butadiene to prevent cancer metastasis.
The present invention provides a method of using (E)-1-(3', 4'- dimethoxyphenyl) butadiene to induce anti-tumorigenic effects in pancreatic carcinoma, ovarian carcinoma and prostate carcinoma. The invention also provides a method of using (E)-1-(3', 4'- dimethoxyphenyl) butadiene to prevent cancer metastasis.
The present invention discloses a process for the therapeutic management of diarrhea predominant irritable bowel syndrome in humans comprising the oral administration of Bacillus coagulans SBC37-01, MTCC 5856 (containing not less than 2 billion spores) along with standard treatment of care in a specific manner.
Disclosed is a method of achieving optimal mammalian energy balance using forskolin on a particular physiological and developmental stage of the mammalian cellular system.
Disclosed is a method of achieving optimal mammalian energy balance using forskolin on a particular physiological and developmental stage of the mammalian cellular system.
A61K 31/352 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. cannabinols, methantheline
The present invention discloses novel oligonucleotide primer sequences BC1, BC2 and BC3 for the identification of Bacillus coagidans. The invention also discloses a PCR based method for the identification of Bacillus coagulans using the aforesaid primers, wherein positive amplification with primer sets BC1, BC2 and negative amplification with primer set BC3 confirms the presence of Bacillus coagulans.
C12Q 1/04 - Determining presence or kind of microorganismUse of selective media for testing antibiotics or bacteriocidesCompositions containing a chemical indicator therefor
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
67.
Composition comprising scirpusin A and scirpusin B and anti-obesity potential thereof
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A01N 31/08 - Oxygen or sulfur directly attached to an aromatic ring system
A01N 37/12 - Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group , wherein Cn means a carbon skeleton not containing a ringThio-analogues thereof
A01N 31/08 - Oxygen or sulfur directly attached to an aromatic ring system
A01N 37/12 - Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group , wherein Cn means a carbon skeleton not containing a ringThio-analogues thereof
A01N 31/08 - Oxygen or sulfur directly attached to an aromatic ring system
A01N 37/12 - Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group , wherein Cn means a carbon skeleton not containing a ringThio-analogues thereof
Disclosed are methods of managing obesity and hypercholesterolemia using a composition of matter comprising the ethyl acetate fraction of the extract of Cyperus rotundus rhizomes standardized to contain 5% of total stilbenes.
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A method of solubilizing curcuminoids is disclosed wherein the method uses polyvinyl pyrrolidone and sodium bis (2-ethylhexyl) sulfosuccinate and the aqueous solubility of curcumin/curcuminoid mixtures is enhanced to more than 10%- 15% w/v in water. The present invention also pertains to a curcuminoids composition characterised by not less than 10% w/v, more specifically between 10%- 15% w/v aqueous solubility of curcuminoids in water.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
A61K 35/742 - Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
Disclosed is the a method of effecting skin hydration and enhancing skin barrier function, said method comprising the step of bringing into contact a pentapeptide conjugate of oleanolic acid with skin cells so that the effect of increased cellular communication at the molecular level to bring about gene and protein expression in the cells of the skin that enable hydration and skin barrier functions are realized.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
A61K 35/742 - Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
C12P 7/64 - FatsFatty oilsEster-type waxesHigher fatty acids, i.e. having at least seven carbon atoms in an unbroken chain bound to a carboxyl groupOxidised oils or fats
A01G 1/00 - Horticulture; Cultivation of vegetables (labels or name-plates G09F 3/00, G09F 7/00)
A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
78.
Synthesis of calebin-A and its biologically active analogs
C07C 67/10 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond
C07C 67/11 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond being mineral ester groups
Disclosed is a therapeutic management method of hypercholesterolemia in mammals. More specifically, the present invention relates to a method of reducing high levels of circulating cholesterol (hypercholesterolemia) in the blood stream of mammals, said method involving step of administering therapeutically effective amounts of Calebin A to said mammals to bring about the effects of (i) reducing the amount of total blood cholesterol levels; (ii) reducing the concentrations of low density lipoproteins (LDL) and very low density lipoproteins (VLDL); (iii) increasing the concentrations of high density lipoproteins (HDL) and (iv) reducing concentrations of serum triglycerides.
Disclosed is a therapeutic management method of hypercholesterolemia in mammals. More specifically, the present invention relates to a method of reducing high levels of circulating cholesterol (hypercholesterolemia) in the blood stream of mammals, said method involving step of administering therapeutically effective amounts of Calebin A to said mammals to bring about the effects of (i) reducing the amount of total blood cholesterol levels; (ii) reducing the concentrations of low density lipoproteins (LDL) and very low density lipoproteins (VLDL); (iii) increasing the concentrations of high density lipoproteins (HDL) and (iv) reducing concentrations of serum triglycerides.
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A01N 31/08 - Oxygen or sulfur directly attached to an aromatic ring system
A01N 37/12 - Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group , wherein Cn means a carbon skeleton not containing a ringThio-analogues thereof
The present invention discloses the potential of Calebin A in inhibiting adipogenesis and applications thereof in obesity management. The present invention elucidates the potential of Calebin A to favorably modulate biochemical markers associated with obesity. Notable biomodulatory properties of Calebin A include inhibiting leptin production, increasing adiponectin expression and inhibiting local (adipocyte) and systemic inflammation caused by pro-inflammatory cytokines Tumor Necrosis Factor (TNF-α), Interleukin-6 (IL-6) and Interleukin-1 (IL-1β).
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A61K 8/64 - ProteinsPeptidesDerivatives or degradation products thereof
A61Q 17/00 - Barrier preparationsPreparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
A61K 8/97 - Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from algae, fungi, lichens or plantsCosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof, of undetermined constitution from derivatives thereof
A61K 8/368 - Carboxylic acidsSalts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
A61Q 17/04 - Topical preparations for affording protection against sunlight or other radiationTopical sun tanning preparations
A61K 36/889 - Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
The present invention discloses the potential of Calebin A in inhibiting adipogenesis and applications thereof in obesity management. The present invention elucidates the potential of Calebin A to favorably modulate biochemical markers associated with obesity. Notable biomodulatory properties of Calebin A include inhibiting leptin production, increasing adiponectin expression and inhibiting local (adipocyte) and systemic inflammation caused by pro-inflammatory cytokines Tumor Necrosis Factor (TNF-α), Interleukin-6 (IL-6) and Interleukin-1 (IL-1β).
The present invention relates to a method of inhibiting pro-inflammatory and T-cell mediated cytokines, said method comprising step of administering to a subject in need thereof a therapeutically effective amount of colocynthin and/or its derivatives. The invention also relates to a method of inhibiting T-cell surface markers and to a method of regulating immune response by colocynthin and/or its derivatives.
A61L 2/00 - Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lensesAccessories therefor
A61K 36/00 - Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
90.
Compositions and its use in treating obesity or inducing weight loss
The present invention provides a composition comprising polyisoprenylated benzophenone derivative and at least one component selected from stilbene derivative and anthocyanins. The composition inhibits adipogenesis and is therefore useful in treating obesity or weight loss.
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
C12N 5/02 - Propagation of single cells or cells in suspensionMaintenance thereofCulture media therefor
91.
OLEANOYL PEPTIDE COMPOSITION AND A METHOD OF TREATING SKIN AGING
The present invention relates to a composition containing peptide of SEQ ID No. 1 linked to oleanolic acid and a method of treating skin aging. The composition effectively reduces signs of ageing due to oxidation, collagen insufficiency and excess activity of serine proteases like elastase and collagenase that result in wri nkling of skin, fine expression lines, reduced skin thickness, hyperpigmentation, under eye dark circles, and premature ageing.
Disclosed is a novel synthetic method for isomeric peptides through an appropriate linkage of L-selenomethionine or Se-Methyl-L-selenocysteine with L-glutamic acid. The novel synthetic method produces isomeric peptides of L-selenomethionine or Se-Methyl-L-selenocysteine that exhibit (i) enhanced water solubility; (ii) enhanced rate of dissolution in water; (iii) enhanced bioavailability; (iv) excellent vascular endothelial growth factor promoting activity; (v) excellent anti-5-alpha-reductase activity; (vi) capabilities to prevent/reduce “hair fall” and promote “hair growth”, thereby maintaining a perfect homeostasis for “hair care”. Cosmeceutical and pharmaceutical compositions comprising the isomeric peptides obtained through an appropriate linkage of L-selenomethionine or Se-Methyl-L-selenocysteine with L-glutamic acid are also disclosed. Other dipeptides with several other amino acids and uses thereof are also disclosed.
Disclosed are novel protective compositions for dermal papilla cells. In an embodiment the protective compositions of the present invention comprise 0.25% w/w or above of compositions comprising at least 10% w/w and above of 1 -O-galloyl- β-D-glucose (β-glucogallin). In an embodiment, the said protective composition additionally comprises 50% to greater than 50% gallates including mucic acid 1, 4-lactone 5-0- gallate, mucic acid 2-O-gallate, mucic acid 6-Methyl ester 2-O-gallate, mucic acid 1 -Methyl ester 2-O-gallate and ellagic acid. In another embodiment the invention also encompasses synergistic protective compositions comprising the said protective compositions and 0.5% concentrate of liquid endosperm of Cocos nucifera, for dermal papilla directed towards helping the dermal papilla cells to form sufficient numbers and to retain a healthy morphology conducive for hair growth.
The present invention relates to a composition containing peptide of SEQ ID NO: 1 linked to oleanolic acid and a method of treating skin aging. The composition effectively reduces signs of ageing due to oxidation, collagen insufficiency and excess activity of serine proteases like elastase and collagenase that result in wrinkling of skin, fine expression lines, reduced skin thickness, hyperpigmentation, under eye dark circles, and premature ageing.
The present invention relates to a method of treating CNS disorders, particularly Alzheimer's disease. The method comprise step of administering to a subject in need thereof a therapeutically effective amount of hydroxychavicol and/or its derivatives or a composition comprising hydroxychavicol and/or its derivatives optionally along with pharmaceutically acceptable excipients. The invention also relates to use of hydroxychavicol and/or its derivatives for treating hyperpigmentation.
A01N 65/00 - Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
96.
INOTILONE DERIVATIVES AS COHERENT BIOLOGICAL RESPONSE MODIFIER (CBMR)
Optimal compositions of derivatives of 5-methyl-3(2H)-furanone compounds and phenylpropanoid polyketides related to inotilone, that exert biological response modification in health and disease, and their method of preparation, are disclosed. Methods of treating degenerative conditions stemming from over-expression of inducible nitric oxide synthase (iNOS) using these compositions are also disclosed.
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
A61K 31/27 - Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, e.g. meprobamate, carbachol, neostigmine
97.
NOVEL HYDRO-ALKOXYL CITRONELLAL COMPOUNDS-SYNTHETIC ROUTES, COMPOSITIONS AND USES THEREOF
Disclosed are new chemical entities 2, 3, 7-trimethyl-7-alkoxy-octanals, represented by the general structure (STR#GEN) wherein "R" represents an alkyl, allyl, alkenyl, or aryl alkyl groups. In specific the present invention discloses novel hydro-alkoxyl citronellal compounds represented by STR#I, Il and III to generate new flavor and/or aroma materials. The use of compounds of the present invention as a part of perfume and aroma (fragrance) compositions is also disclosed by the invention.
Cocos nucifera, for dermal papilla directed towards helping the dermal papilla cells to form sufficient numbers and to retain a healthy morphology conducive for hair growth.
A61K 36/00 - Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
99.
MELANOGENESIS INHIBITION BY 3, 5-DIMETHOXY-4'-HYDROXYSTILBENES AND COSMECEUTICAL COMPOSITIONS THEREOF
Disclosed is the cosmeceutical potential of 3, 5-dimethoxy-4'-hydroxystilbene in terms of its melanogenesis inhibitory and photo protective activities. Also disclosed does a topical melanogenesis inhibitory composition comprising 0.01 to 50% by weight of 3, 5- dimethoxy-4'-hydroxystilbene.
A01N 43/04 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atom with one hetero atom
Disclosed is the most optimal biomarker for the BIOLOGICAL POTENCY of Emblica Officinalis Gaertn. (AmIa) fruit and products standardized for 5% and above w/w of the said biomarker. Further, the products described herein contain from about 0.0001 0 % to about 4% of free ascorbic acid depending on the raw material used. The optimal biomarker for amla described herein above is represented by STR#1.
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