**1. Introduction**

 According to the American National Institute of Health (NIH), biomaterial is defined as "any substance or combination of substances, other than drugs, synthetic or natural in origin, which can be used for any period of time, which augments or replaces partially or totally any tissue, organ or function of the body, in order to maintain or improve the quality of life of the individual" [1]. The advances led to a pronounced increase in the range of use and efficacy of biomaterials over time. Thus, biomaterials have become critical components used in many industries,

including medical devices, dental restoratives, and drug delivery, and are increasingly being used in technological applications such as in vitro diagnostics [2, 3].

These materials must be biocompatible at the material-tissue interface: "ability of a biomaterial to perform its desired function with respect to a medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response to that specific situation" [1]. In dentistry, biomaterials are used in restorative procedures, such as dental restorations; dentures; dental implants; surgical procedures; and endodontic materials. Most dental biomaterials are classified as devices, including filling materials, diagnostic aids, cements, bonding agents, and implants [1, 4, 5]. In addition, commercial mouthwashes are used as antiseptics for better oral hygiene. Therapeutic mouthwashes reduce bacterial counts, have antiplaque effects, work as an astringent, and help to reduce gingivitis and carious lesions [6, 7].

Dental materials should not be toxic, irritant, or corrosive and should be easy to use. The biomaterials used in dentistry can be metals (amalgam of silver, titanium, and gold), ceramics (feldspar, alumina, zirconia, porcelain reinforced with silica), composites [1], materials that can optimize dentin bonding, and mouthwashes. However, in the field of health, the use of natural products for dental biomaterials and curing of diseases has always emphasized, rather than depending on the conventional allopathic medicine [7].

Following this trend, in addition to the devices and materials themselves, biological advances have revolutionized the methods used in the chemical and material industries to produce and transform raw materials. Living plants can be processed in large quantities to produce a much larger variety of liquids and materials, without the cost of energy or effluent streams—typical by-products of the chemical industry. Nature is not only capable of allowing the synthesis of new chemical substances but also significantly reducing the costs and environmental impacts associated with the manufacture of current chemicals and drugs [3].

In 1978, the World Health Organization (WHO) recognized medicinal plants as a therapeutic resource [8]. The Ordinance No. 971 dated May 03, 2006, approved the National Policy on Integrative and Complementary Practices (PNPIC) in the Unified Health System (SUS) in Brazil, including the use of phytotherapy [9]. At present, phytotherapy is defined as a science-based practice for the treatment of diseases, which uses medicinal plants, plant drugs, and preparations, not including substances from another source [10]. Therefore, biomaterials made today are routinely information rich and incorporate biologically active components derived from nature [2, 3, 5, 7]. Today, the variety of natural products used in the biomaterials for dental and oral health care may include natural silk [11], propolis [12–15], chitosan [16], herbal tea [17], and miswak [18], as well as natural products for bone repair such as dolomite [4].

 Since phytotherapy is a feasible method for the control and prevention of the development of oral pathologies, with the additional possibility of incorporating phyto-derived compounds into biomaterials, the discovery of new phytotherapic compounds has been of high relevance to dentistry [5, 14, 19–22]. Brazil has an advantage in this market because it has the greatest biodiversity in the world, especially in the Amazo nian Region, and a genetic heritage of great potential for the development of new herbal products [23], especially in dentistry. Given the growth of products derived from medicinal plants in Brazil, it was necessary to implement a statute that covered the requirements for all medicines and/or biomaterials to ensure the quality, efficacy, and safety of these products. In this sense, the Brazilian National Health Surveillance Agency (ANVISA) establishes product quality control requirements, involving stages ranging from obtaining of raw materials through to the qualitative and quantitative characterization of their active principles [24, 25].

*Biopharmaceutical Products and Biomaterials of the Amazon Region Used in Dentistry DOI: http://dx.doi.org/10.5772/intechopen.82056* 

The official recognition of phytotherapy in dentistry in Brazil was accompanied by several gaps in scientific research on medicinal plants, specifically for plant species with applications in diseases of the oral cavity. The state of Amazonas, specifically the city of Manaus, did not have a diagnosis of the applicability of medicinal plants in dental services. In this sense, these researchers conducted an ethnobotanical study to identify the main plants used for pathogenesis of the oral cavity, with the aim of reducing their empirical use and favoring the use of medicinal plants based on scientific evidence [10].

The search for the biomaterials, their development, and pharmaceutical forms comprises products derived from medicinal plants with compounds that are safe and have proven quality. Thus, researches in dentistry have been developed with the objective of searching for new bioactive principles for the formulation of drugs with different types of applications, capable of acting in both preventive strategies and curative treatments, thus encouraging the use of phytotherapic agents such as *Copaifera multijuga*, *Apis mellifera* (propolis), and *Libidibia ferrea*.

## **2.** *Copaifera multijuga***—copaiba oil**

According to the growing interest in antimicrobial agents derived from medicinal plants, natural products are considered an excellent alternative to synthetic chemicals. Amazonian biodiversity products that have been used for years in folk medicine have emerged as feasible and promising alternatives for inhibiting microorganisms in dental biofilm. Copaiba oil—as it is popularly called—a phytotherapeutic agent widely used by the Amazonian population, is known for its antibacterial, antiinflammatory, anesthetic healing and antitumoral medicinal properties.

The studies developed with copaiba oil have complied with all the norms required. The *Copaifera multijuga* Hayne species were collected from official research institutions (National Research Institute of Amazonian—INPA) to guarantee the legitimacy of the species. The exsiccata was stored in the INPA Herbarium under No. 270709.

#### **2.1 Antibacterial activity of copaiba oil formulations**

The first reports demonstrated the use of copaiba oil as an effective agent against the etiological agents of caries disease, as seen in Ref. [26]. This research demonstrated the antibacterial activity of calcium hydroxide and zinc oxide pastes associated with essential oil and *C. multijuga* resin against *Streptococcus mutans*. The bacteriostatic and bactericidal activities of the oil *in natura* against the same microorganism were also reported, giving rise to a line of research in dentistry in the search of scientific evidence.

*C. multijuga* Hayne has presented promising antibacterial activity against *S. mutans, S. mitis*, *S. salivarius*, *S. constellatus*, and *S. sanguinis* from the copaiba gel production for the dental biofilm control [27]. In addition, evidence was shown of antibacterial activity against *Enterococcus faecalis* and *Candida albicans* present in endodontic flora, biological compatibility test in the teeth of rats and dogs using the copaiba oil as vehicle for calcium hydroxide [26], biological compatibility test in gingival tissue and a physical-chemical study and antibacterial activity dental cement to suit the conditions of the oral environment [28], and antibacterial activity in copaiba oil emulsions, as shown in **Table 1** [22].

The results of the chromatographic analysis of *C. multijuga* oil revealed that the structures of its components are made up of various sesquiterpenes, primarily being constituted of β-caryophyllene and its oxide, forming its biological activity [26–28].


#### **Table 1.**

*Minimum inhibitory concentration (MIC) of copaiba emulsions against microorganisms.* 

In [29], a high proportion of sesquiterpenes (88.55–98.05%) was revealed in the copaiba oils analyzed, with β-caryophyllene being the main type.

## **2.2 Copaiba oil emulsion as dentin biomodifier**

Different approaches have been proposed to improve the restorative material bond to the dental structure by optimizing the infiltration of resinous monomers into the demineralized dentin and reduce the rate of water absorption and collagen degradation, by means of such as the application of an additional layer or multiple layers of a hydrophobic adhesive agent [30], vigorous solvent evaporation [31], polymerization, and the use of electric current to improve impregnation of the monomers [32].

Metalloproteinases (MMPs) trapped in the extracellular matrix are calciumdependent and zinc-activated enzymes that mediate the denaturation of the extracellular matrix through collagenase (MMP-8 is the major collagenase in human dentin) and gelatinase (MMP-2 and MMP-9), as well as the enamelysin MMP-20 and the stromelysin MMP-3, which are naturally entrapped in the mineralized dentin during odontogenesis [33]. Since the bonding process occurs as a result of encapsulation of the collagen by the adhesive system, it is necessary to inhibit these enzymes to preserve the adhesive interface from proteolytic and hydrolytic degradation, by forming the hybrid layer [34].

#### **Figure 1.**

*Effect of copaiba oil on metalloproteinase (MMP) activity (gelatin zymography).* 

*Biopharmaceutical Products and Biomaterials of the Amazon Region Used in Dentistry DOI: http://dx.doi.org/10.5772/intechopen.82056* 

In recent studies, a zymography assay was performed with HT1080 cells. This demonstrated that the copaiba oil emulsion (CO) as dentin biomodifier showed the potential to inhibit matrix metalloproteinases −2 and −9 (**Figure 1**).

In the time of 30 seconds, statistical difference in the decrease of the MMP-9 activity was observed among all solutions tested when compared with the control group without treatment. In the time of 10 minutes, there was a statistical difference only between chlorhexidine (CLX), 10% CO + 0.3% CV, and 10% alkaline CO. At 20 minutes, the only solution that presented a statistical difference in the decrease of MMP-9 activity was the 10% CO + 0.3% CV. The best result obtained was with 10% alkaline CO in a time of 10 minutes, with a 35% decrease in MMP-9 activity (**Figure 2A**).

A decrease in the MMP-2 enzymatic activity was also observed. At 30 seconds, there was a statistical difference between the CLX solution and the copaiba oil emulsion at 0, when compared to the control group. At 10 minutes, a statistical difference was observed in the CLX solution and the alkaline CO, each presenting a 44 and 67% reduction in enzyme activity, respectively. Finally, at 20 minutes, there was a statistical difference in the CLX solution (21%), in the COs 0.3% (42%) and 0.6% (53%), and in the alkaline CO (**Figure 2B**).
