The international patent was initially filed in March 2020 and published in December 2020, but a few weeks ago Unilever filed a Chapter II demand which called for the international examination to involve interaction between the personal care major and the examiner, not required under a regular Chapter I patent filing.
Writing in its international patent filing, Unilever said it had developed a toothpaste formulation containing zinc salt that could be used for lowering blood pressure.
Whilst zinc salts had been used in oral care compounds for several years, it said inclusion was primarily for oral care benefits like anti-plaque or preventing gingival and periodontal tissue damage.
“However, the present application has found that the presence of zinc in an oral care composition can deliver a benefit of the body in addition to oral care benefits,” Unilever wrote.
Mechanism of action - zinc salts enhance nitrate reductase activity
Explaining its finding in more detail, Unilever said the zinc salt composition increased nitrite levels in the oral cavity via enhanced nitrate reductase activity [Enzyme Commission number EC: 18.104.22.168]. Then formulation boosted the expression of the Kegg Orthologies KO0370, KO0371, KO0373 and KO0374 – a set of specific genes and associated pathways that resulted in certain molecular functions, identified in the Kegg Orthology database developed by the Kyoto University in Japan.
“Enhanced nitrate reductase activity and hence increased nitrite levels has been cited in the academic literature to have associated health benefits such as promoting cardiovascular health and or vasodilation, in particular reducing blood pressure,” Unilever wrote.
The personal care major backed findings with a six-week clinical study looking at the effect of its product, containing zinc citrate trihydrate, on the oral microbiome. The study measured dental plaque at the beginning and end of the study which was analysed for microbiome gene activity following RNA extraction.
“Analysis of nitrate reductase [E.C: 22.214.171.124] gene expression associated with the examples (…) showed the following: A significant increase [T-test, p value < 0.05] in the expression of this gene was observed for the zinc product compared to the control product at six weeks of product use,” Unilever said.
“The examples demonstrate use of a zinc containing toothpaste significantly increases the expression of the gene involved in the conversion of nitrate to nitrite compared to a control toothpaste.”
Zinc citrate ‘preferable’ in formulation blend
Unilever said it was important the zinc salt was present in the formulation at 0.5 to 3.0 wt% and was comprised pf water-soluble or sparingly water-soluble sources of zinc ions like zinc chloride, zinc acetate or zinc fluoride, but preferably zinc citrate.
Various other ingredients could be incorporated into the formulation, it said, to “enhance performance and/or consumer acceptability”, including abrasive materials like silicas and calcium carbonates, gelling and thickening agents like amorphous silicas and tooth whitening agents; preferably a green or blue pigment that was insoluble in human saliva.
The composition could also include a remineralising calcium source like calcium silicate and other ingredients “common in the art” such as antimicrobial, anti-inflammatory and anti-caries agents, vitamins, plant extracts, flavours and preservatives, Unilever said.
WIPO International Patent No. WO/2020/244822
Published on: December 10, 2020. Filed on: March 17, 2020.
Chapter II demand published: March 25, 2021. Chapter II demand filed: March 4, 2021.
Title: “Use of oral care composition”
Inventor: Unilever – SE. Adams et al.