**5. Patenting of processes and products aimed at pulmonary injury by smoke inhalation: any evidences?**

Besides the two products mentioned and highlighted in the previous topic, since they were the first and the last to be patented, we had three other products studied and patented, e.g., "antithrombin III (ATIII) and heparin," which refers to the exogenous administration of ATIII—a direct inhibitor of thrombin, and heparin, that inhibits coagulation proteases, decreasing fibrotic conditions and improving gas exchange in animal models of acute pulmonary injury. Since there were six patents deposited aimed at the use of this product, it was found that the inhaled administration (using a compressor nebulizer, an ultrasonic nebulizer, or a dry powder inhaler) is more efficient than intravenous injection [28]. The dose used was also mentioned in the patent, stressing that the inhalation of combined products can also be performed according to the need or symptom occurrence [29].

In five other patents, "estrogen receptor-β (ERβ)-selective ligands or compositions," with the objective of treating or preventing acute pulmonary injuries due to local inflammatory processes (smoke inhalation, prematurity with surfactant deficiency, oxygen toxicity, barotrauma by mechanical ventilation with positive pressure) or peritonitis or intravenous bacteremia, both during sepsis, were studied. Furthermore, many preclinical trials proved the anti-inflammatory properties of estrogen [29–31].

Finally, the patent on "anti-IL-8 and anti-L-selectin," which we found only one patent deposited. L-selectin's role in immunity control is as a receptor in T cells. The smoke inhalation model in sheep of Murakami and Traber [32] showed that the

*Intellectual Property Rights - Patent*

victims of this type of injury.

not discern.

widely known.

eosinophils [2, 8].

inhalation.

agent [24].

**by smoke inhalation**

likely that in the future this resource will contribute to the best clinical outcome for

It is known, however, that the best clinical outcome for the victim of inhalation injury depends on other factors. According to Bedri et al. [22], socioeconomic and ethnic factors and the sex of the victims influence the clinical outcome. They found that Afro-descendent Americans, female and uninsured, had more complications, more surgical interventions, longer hospital stay, and higher mortality rates, even though lower body surface area burned and there is a lower proportion of inhaled lesion. These disparities further emphasize the need for further research on the underlying racial and socioeconomic factors that this review of the database could

In turn, natural products present great therapeutic potential and are the subject of study in several experimental, in vitro, and/or in vivo research. The low cost, the good availability, and the habitual use by the population, considering the regional

The terpene group deserves special mention, both for being part of traditional medicine for centuries and for having a low toxicity [23]. In addition to being used in the food and cosmetic industries, its effects, anti-inflammatories, antioxidants, analgesics, anticonvulsants, antidepressants, anxiolytics, anticancer, antitumor, neuroprotective, antimutagenic, antiallergic, antibiotics, and antidiabetics, are

Examples are carvacrol, linalool, borneol, limonene, myrene, and pinene. It is known, for example, that D-limonene has important immunomodulatory properties, ameliorating attacks of atopy and asthma, besides inhibiting the action of cytokines and release of substances reactive to oxygen and containing migration of

**4. Historical background of patents aimed to control pulmonary injury** 

Two years ago, our research group performed a patent review [24] in three different databases, and only 18 patents, containing the keywords "smoke inhalation" in the title, abstract, or full text, fit in the inclusion criteria for this research. There was a language bias, making it possible for many other patents to exist, regarding the use of natural and synthetic products developed for the treatment of smoke inhalation, but we believe that the results presented provide the reader a perspective on current therapeutic options and new approaches and treatments for smoke

The oldest patent was deposited in 1977 and was on "orgotein," which is the generic name of the enzyme superoxide dismutase (SOD), which belongs to the metalloprotein group, contains copper and zinc, and was first described in 1969 by McCord and Fridovich. Those researchers found that a bovine protein (orgotein) was an enzyme that could catalyze the destruction of superoxide radicals through a disproportion in molecular oxygen and hydrogen peroxide. By destructing free superoxide radical, SOD contributes to the physiological balance between prooxidants and antioxidants, being known for being a potent anti-inflammatory

Dominguéz [25] reported that orgotein is a naturally occurring protein inside a human cell and, when topically and systematically administered, produces physiological effects that do not manifest or manifest in a lower degree by the natural SOD of a patient. This exogenous manifestation decreases the amount of acute

inflammatory events and influences late effects.

popular knowledge, are some of the factors that contribute to this reality.

**64**

anti-L-selectin antibody significantly alleviated airway obstruction. The neutrophil treatment with anti-L-selectin antibody reduces neutrophil capacity of adherence to the endothelium. It is also probable that chemokines such as IL-8 and others direct the neutrophil movement from the vasculature [33]. According to this patent, the effects on vascular permeability may point that both anti-IL-8 and anti-L-selectin decrease the lesions of endothelial cells.

These data help highlight the different means of treatment of injuries caused by smoke inhalation and the drugs being studied to control such injury. We presented the significant progress achieved in the field, demonstrating the growing interest of scholars and pharmaceutical companies in the development of products with the potential to be successful in treatment of smoke inhalation.
