Table 1.
Pharmaceutical product patents with natural origin published by EPO from 2016 to 2022.
| Year | Country | Registration Number | Species | Part of the Plant | Secondary Metabolites | Mechanism of Action | Formulation | Safety Assessments | Efficacy Tests | Ref |
|---|---|---|---|---|---|---|---|---|---|---|
| 2020 | WO | WO2020115767 (A1) | Premna herbacea | Leaves | isoverbascoside | Improved insulin signaling via the AKT/AM PK pathway | ND | A single dose of 2000 mg/kg of P. herbacea methanol extract was reported as safe after acute toxicity evaluation in Swiss ICR male mice. | In vitro: [a] Uptake of glucose in L6 cells [b] Total accumulation of lipids in HepG2 cell lines by staining with oil red 0 In vivo: ND Clinical studies: ND |
[25] |
| 2020 | US | US11007237 (B2); US2020147160 (A1) | Pinus spp. | Resin | ND | α-glucosidase inhibition | Syrup, tablets, capsules, granules, and powders. | ND | In vitro: [a] Suppression of α-glucosidase activity [b] Ability to uptake glucose Clinical studies: ND |
[26] |
| 2020 | WO | WO2020012299 (A1) | Curcuma longa, Phylanthus emblica | ND | ND | Insulin sensitization and antihyperglycemic | ND | Efficacy studies were carried out with non-cytotoxic doses after evaluation of cytotoxicity and PPAR γ expression in fibroblasts using the MTT assay. | In vitro: [a] Evaluation of PPAR γ expression in fibroblasts cell culture. In vivo: Evaluation of streptozotocin-induced insulin resistance in rats. Clinical studies: ND |
[27] |
| 2019 | SG | SG11201908574T (A) | Curcuma longa, Emblica officinalis, Vernonia anthelmintica, Tinospora cordifolia, Trigonella foenum-graecum, Ixora coccinea, Syzygium cumini | ND | Tannins, organic acids, curcuminoids | ND | Powders, pastes, granules, capsules, tablets, emulsions, suspensions, syrup, elixir, oral drops, and nutraceuticals | Acute toxicity test in male and female Swiss ICR mice, at doses. It was reported as safe. | In vitro: [a] Evaluation of glucose uptake potential in L6 cells [rat skeletal muscle cells] In vivo: ND Clinical studies: ND |
[28] |
| 2019 | WO | WO2019205943 (A1) |
Polygonatum spp., Poria cocos, Lycium barbarum, Pueraria Panax ginseng, Shiitake, cordyceps, Ganoderma lucidum, Hericium erinaceus, Tremella Dendrobium officinale |
ND | Flavonoids and oligosaccharides (inulin, fructooligosaccharides, oligosaccharides) | Reduction in the proportion of Firmicutes/Bacteroides in the gastrointestinal tract. | ND | The description of the methodology was not detailed, but it was concluded that the preparation is safe. | In vitro: AND In vivo: Oral glucose tolerance test in different groups of mice. Clinical studies: ND |
[29] |
| 2019 | WO | WO2019186579 (A1) | Trigonella foenum-graecum, Solanum lycopersicum, Dudhi bhopla, Lagenaria siceraria, Vitis vinifera, Medicago sativa | Roots, stems, leaves, buds, flowers, fruits, and seeds. | Osmotin | Adiponectin agonists/mimetics. Activation of the AMPK pathway | Tablets, syrup, granules, and film for transmucosal administration. | ND | In vitro: ND In vivo: ND Clinical studies: ND |
[30] |
| 2019 | US | US10967025 (B2) US2019209634 (A1) | Moringa Oleifera, Origanum vulgare, Shilajit, Blue-Green Algea, Phyllanthus emblica, Piper nigrum, Salvia rosmarinus, Punica granatum, Trigonella foenum-graecum, Curcuma longa. | Leaves, fruits, and seeds. | Polyphenols, carvacrol, phycocyanin | Antioxidant and anti-inflammatory—via COX-1 inhibition | Capsules | ND | In vitro: [a] ROS absorption capacity [b] DPPH radical scavenging activity [c] Oxidation of LDL in a cell-free system [d] Insulin release in islets of rats [e] Effect on cholesterol absorption in Caco-2 cells [f] Effect on COX-1 Enzyme activity. In vivo: ND Clinical studies: ND |
[31] |
| 2019 | WO | WO2019088958 (A2); WO2019088958 (A3) | Paiiurus spina-christi | Fruits | Naringenin | Effect on ALT and AST regulation enzyme levels, antioxidant activity, increased insulin secretion, regulates blood glucose, and increased magnesium absorption |
ND | ND. | In vitro: ND In vivo: Rats with streptozotocin-induced diabetes Clinical studies: ND |
[32] |
| 2019 | MX | MX2018004489 (A) | Agavaceae spp. | Leaves, rhizomes, and mead | Steroidal saponins and sapogenins (kammogenin, manogenin, gentrogenin, and hecogenin). | Lipid and glucose metabolism improvements, energy expenditure, gut microbiota health, muscle oxidative capacity, and thermogenesis, stimulating PGC-1Q and UCP1, and activating AMPK | Pills, capsules. | ND | In vitro: ND In vivo: ND Clinical studies: ND |
[33] |
| 2019 | US | US10640480 (B2); US2019031635 (A1) | Gnetum gnemon | Fruits | Gnetin C | Antioxidant, antibacterial, inhibition of lipase enzymes, α-glucosidase, and α-amylase. | Powders, granules, tablets, capsules. | ND | In vitro: ND In vivo: ND Clinical studies: ND |
[34] |
| 2019 | AU | AU2018278958 (A1); AU2018278958 (B2) |
Cichorium endivia, Latifolium; Lactuca sativa, Longifolia; Lactuca sativa. Plantas das famílias Asteraceae spp., Lamiaceae spp., Brassicaceae spp., Amaranthaceae spp. |
Fruits, leaves, stems, and roots | ND | IRS2 branch activation of the insulin-mediated signal transduction cascade. | N.D. | ND | In vitro: ND In vivo: ND Clinical studies: ND |
[35] |
| 2019 | US | US10576117 (B2); US2019125816 (A1) | Salacia chinensis, Gymnema sylvestre, Emblica officinalis, Eugenia jambolana, Curcuma longa, Commiphora mukul, Tinospora cordifolia. Ithania somnifera, Terminalia chebula, Andrographis paniculata, Boerhavia diffusa, Azhadirachta indica, Aristolochia indica, Aegle marmelos, Cyperus rotundus, Hemedesmus indicus, Trichosanthes dioica, Santalum alba, Terminalia arjuna, Woodfordia fruiticosa, Glycerrhiza glabra, Mucuna pruriens, Myrica nagi, Plumbago rosea, Inula racemosa, Zingiber officinalis, Piper longum y Piper nigrum | Roots, fruits, bark, leaves, heartwood, flowers, seeds, rhizomes, gum resin, and stems. | ND | Lipids/cholesterol reduction, tissue phosphatases, and tissue transaminases reduction, reversal of glycogen depletion, pancreatic islets cell regeneration, hypoglycemic, hypolipidemic, cytoprotective, and immunomodulatory action. FBS, PPBS, HbA1C reduction | Tablets, granules, capsules, solution, emulsion, suspension | According to OECD guidelines in rodent tests 423, 407, 408, and 452. It was reported as safe. | In vitro: ND In vivo: Model of diabetes in Wistar rats diabetic by alloxan. Clinical studies: A prospective, open-label, non-randomized, phase III clinical trial conducted in outpatients at Muniyal Ayurvedic Hospital and Research Centre, Manipal, India. |
[36] |
| 2017 | US | US10668122 (B2); US2017252393 (A1) | Toona sinensis | leaves | Monoterpenes, diterpenes, triterpenes, sesquiterpenes, saturated and unsaturated fatty acids | Glucose absorption improvements, lipid degradation, inhibition of large lipid clusters, and inhibition of metabolic syndrome | ND | ND | In vitro: 24 h glucose consumption of 3T3-L1 adipocyte culture medium. 2- Adipogenesis blocked by TS-SCF in adipocytes 3- Antidiabetic effect of high to medium/high polar components of TSL, except TSL-SCF In vivo: ND Clinical studies: ND |
[37] |
| 2017 | US | US10111923 (B2); US2017173103 (A1) | Cyclocarya paliurus, Puerariae lobatae Radix, Polygonati odorati Rhizoma. L | ND | ND | ND | Pills, capsules, granules, powders, or tea formulation | ND | In vitro: ND In vivo: Rats with streptozotocin-induced diabetes Clinical studies: ND |
[38] |
| 2017 | NZ | NZ630125 (A) | Calophyllum inophyllum | Cortex | ND | Inhibition of DGAT-1 and SCD-1 enzyme activity | Tablets, coated tablets, capsules, powders, granules, elixir, and syrup. | ND | In vitro: 1- Assay of DGAT-1. 2- Inhibition of hDGAT-1 3- SCD-1 Assay 4- Triglyceride synthesis assay in HepG2 cells In vivo: Streptozotocin-induced diabetic rats fed a high-fat diet. Clinical studies: ND |
[39] |
| 2016 | US | US2016361341 (A1); US9828442 (B2) | Hirsutella sinensis | ND | Polysaccharides | Hyperglycemia reduction and improvement of insulin sensitivity in humans and animals. | ND | ND | In vitro: ND In vivo: Streptozotocin-induced diabetic rats fed a high-fat diet. Clinical studies: ND |
[40] |
| 2016 | US | US10028930 (B2); US2016228400 (A1) | Ephedra sinica and brown algae concentrate | ND | Fucoxanthin, caffeine, alkaloids such as ephedrine | Thermogenesis potentiator | Extended-release tablets, transdermal patches | ND | In vitro: ND In vivo: ND Clinical studies: ND |
[41] |
| 2016 | US | US10799547 (B2); US2016067294 (A1) | Suaeda japonica | Leaves and seeds | ND | The cytoprotective activity of pancreatic β-cells, hypoglycemic action, insulin secretion increase, improvement of glucose tolerance, and increase of adiponectin content in the blood. | Pills, powders, granules, capsules. | ND | In vitro: ND In vivo: Overfeeding diabetic OLETF mice. ND clinical studies |
[42] |
| 2016 | UA | UA104161 (U) | Equiseti arvensis, Sambucus spp., Hypericum perforatum, Tiliae spp., Polygonum aviculare, Urticae spp. Inula helenium e Mirtilli spp. | Flowers, leaves. Additional plant material: rhizomes and roots | Ascorbic acid, tannins, organic acids, flavonoids, hydroxycinnamic acids | Hypoglycemic action due to exposure to glucagon-like peptide 1 [GLP-1]. Increased insulin levels, improves carbohydrate and lipid metabolism. | ND | ND | In vitro: ND In vivo: Alloxan-diabetic female rats. Clinical studies: ND |
[43] |
Abbreviations: WO: World Intellectual Property Organization (WIPO). xUS: United States. SG: Singapore. MX: Mexico, AU: Australia. NZ: New Zealand.UA: Ukraine, AKT/AM PK: Protein kinase B or AKT / AMP-activated protein kinase. ICR: Cancer Research Institute. PPAR γ: Peroxisome proliferator-activated receptor. COX-1: Cyclooxygenase-1. ROS: reactive oxygen species. DPPH: 2,2-Diphenyl-1-picrylhydrazyl. LDL: low-density lipoproteins. ALT: alanine aminotransferase. AST: Aspartate aminotransferase. PGC-1Q: Peroxisome proliferator-activated gamma recipe coactivator. UCP1: Uncoupling protein 1 or thermogenin. IRS2: insulin receptor substrate 2. FBS: Fasting blood sugar. PPBS: Postprandial blood sugar test. HbA1C: glycosylated hemoglobin. TS-SCF: T. sinensis- supercritical carbon dioxide fluid. TSL-SCF: Hojas de T. sinensis- supercritical carbon dioxide fluid. DGAT-1: Diacylglycerol O-acyltransferase 1. Human hDGAT-1: Diacylglycerol Acyltransferase -1. SCD-1: stearoyl-CoA desaturates.