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. 2022 Dec 27;15(1):85. doi: 10.3390/pharmaceutics15010085

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.