Pharmaceutical preparations

Abstract

Pharmaceutical formulations for topical dental administration or medical (e.g., implant) treatments are disclosed, comprising an effective amount of at least one antimicrobial compound; at least one peroxide source compound; and at least one gel agent. Methods for treating oral anatomical structures are also disclosed. The pharmaceutical formulations and methods of treatment provide oral anatomical benefits to patients, including, for example, reduction or halting of gum recession; reduction or halting of bone recession; reduction or halting of bone loss; reduction or elimination of pain; reduction or elimination of bleeding; reduction or elimination of swelling; enhanced bone regeneration; enhanced soft tissue repair; or combinations thereof.

Description

[Background technology]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This Patent Cooperation Treaty (PCT) application claims benefit of priority to U.S. Patent Application No. 16 / 241,350, filed January 7, 2019, which is a continuation of U.S. Patent Application No. 15 / 355,185, filed November 18, 2016, which is a continuation-in-part of U.S. Patent Application No. 17 / 707,230, filed March 29, 2022, which is a continuation-in-part of U.S. Patent Application No. 11,311,463, which is relied upon and incorporated by reference in its entirety herein.

[0002] The entire disclosure of each publication or patent document mentioned herein is incorporated by reference.

[0003] The initial formation of bacterial plaque begins within minutes of a tooth surface being thoroughly cleaned. To control the continued establishment and maturation of such bacterial plaque, and ultimately the deposition of tartar, basic oral hygiene practices must be followed. These practices typically consist of basic brushing and flossing.

[0004] Periodontitis is an inflammatory condition of the supporting dental tissues and is usually treated by mechanical removal of subgingival and supragingival biofilm. This traditional mechanical treatment, commonly known as scaling and root planing, is not completely effective, but remains the "gold standard" for the non-surgical management of chronic periodontitis. Currently, the most widely accepted definition of scaling and root planing is as follows: 1. Scaling involves instrumenting the crown and root surfaces of the teeth to remove plaque and tartar from these surfaces. This definition of scaling and root planing was published August 29, 2016, with the release of the American Dental Association's July 1, 2015 guidelines for the treatment of gum disease. 2. Root planing is a definitive procedure designed to remove cementum and dentin that are rough and / or infiltrated by calculus or contaminated by toxins or microorganisms. However, this mechanical therapy may fail to reduce or eliminate anaerobic infections at the base of pockets, within the gingival tissue, or in the furcations of multi-rooted teeth. Some periodontal pathogens have been studied and found to migrate into pit-like defects in the cementum and extend further into the exposed root dentin. These have been reported to act as bacterial reservoirs from which recolonization of mechanically treated root surfaces can occur. Bacterial reservoirs that are not eliminated by conventional periodontal therapy can be further suppressed using various adjunctive therapies that have been investigated to improve clinical outcomes, namely, by the use of chemotherapeutic agents. Various locally delivered chemotherapy agents are available: tetracycline fibers, metronidazole gel, minocycline ointment and minocycline microspheres, chlorhexidine chips, doxycycline hyclate, sodium bicarbonate and 3% hydrogen peroxide, antimicrobial dentifrices, mouthwashes such as Listerine, chlorhexidine, sanguinaria, nonsteroidal anti-inflammatory agents, irrigation, and lasers. Thus, bacterial reservoirs not eliminated by the incomplete mechanical therapy of conventional root planing appliances can be further suppressed by the use of chemotherapy agents.

[0005] Antimicrobial agents or antimicrobial drugs are agents that kill or inhibit the growth of microorganisms. Antimicrobial agents broadly include antiseptics, antifungals, antivirals, antibacterial agents, including antibiotics, and antimicrobial-interactive agents.

[0006] Antiseptics or disinfectants are substances that are applied topically to living tissue to reduce the likelihood of infection, sepsis, or putrefaction. Some antiseptics are bactericidal, while others are bacteriostatic.

[0007] Antifungals or antimycotic agents are fungicidal or fungicidal compositions used to treat and prevent infections.

[0008] Antivirals are medications known to treat viral infections.

[0009] Antibiotics are antibacterial agents. Tetracycline antibiotics are the most commonly used active ingredients in the treatment of periodontitis because they are effective against periodontitis-causing microorganisms and offer better resorption, protein-binding diffusion into tissue structures, and anti-collagenase properties. The high degree of persistence of drugs and agents allows for the control of microbial plaque. Traditionally, such antibiotics are administered orally (e.g., via prescription tablets or capsules) after treatment. Examples of antibiotics that are part of the tetracycline antibiotic family include tetracycline itself, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, and sarecycline. Fluoroquinolone antibiotics are also commonly used active ingredients. Examples include ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, and ofloxacin.

[0010] For several decades, topical antimicrobial therapy in particular has received increasing interest due to the site-specific nature of periodontal infection, the higher possible concentrations of subgingival antimicrobials combined with the reduced side effects of systemic antibiotic use, and the recognition that most clinicians do not possess the skills to properly use periodontal root planing and scaling instruments to achieve reliable periodontal health using mechanical methods alone.

[0011] Of course, it is well known how difficult manual instrumentation can be to perform. For example, it has been found that Cavitron and other sonic instrumentation techniques can only remove about 50% of the calculus and surface roughness from tooth surfaces when scaling and root planing extracted teeth outside the oral cavity.

[0012] Dental care professionals in private practice also often lack the skills or time to sharpen dental scalers and curettes before treating each patient. Most clinicians who perform these procedures do so in a single treatment visit, whether for a single quadrant or up to four quadrants, and with only one attempt at scaling and root planing for each tooth. Busy dental hygiene work schedules and the financial demands and needs of dental offices preclude checking the sharpness of all instruments for proper root planing and scaling before each patient and during treatment without retesting the sharpness as the instruments are used. Instruments become dull when used on the entire mouth, even during the same treatment. Some of this treatment decision-making is dictated by insurance company plans that reimburse on a one-quadrant-per-visit basis, with no additional payment supplemental if the same quadrant is treated over multiple visits. Some hygienists indicate that they sharpen their instruments once or twice a year, or even utilize sonic and ultrasonic instrumentation (albeit with limitations).

[0013] Furthermore, manual scaling and root planing can often be difficult and time-consuming when working without vision in deep pocket areas due to complex and unfavorable root geometries. Multiple studies have supported the benefits of root planing, which can help reduce probing depth, enhance clinical attachment, and inhibit disease progression. While scaling and root planing are localized treatments, they are not always able to remove pathogenic bacteria due to their presence within the periodontal tissues or in deeper pockets where instruments are difficult to reach. As probing depth increases, manual instruments become less effective at seizing the problem root, especially due to deteriorated, unfinished cutting edges provided by various manufacturers and not refined and maintained by clinicians. Studies have shown that cutting edges on most instruments become dull due to deformation of the cutting edge after 15 to 30 strokes against the tooth root. Additionally, multiple studies have reported that the microbiological and clinical effects achieved by ultrasonic debridement, which can be supplemented with root planing and scaling, are similar to those achieved by manual scaling and root planing alone. Interestingly, dental hygiene schools teach students to use ultrasonic and sonic instruments to protect clinical hygienists from occupational injuries, such as carpal tunnel syndrome and other work-related injuries to the wrist, which are often harmful to patients.

[0014] Under ideal research conditions, microbial load drops to 0.1% after mechanical debridement. However, microbial bacteria recolonize within a week with less virulent compositions. In light of this, the concept of one-stage whole-mouth disinfection was introduced in 1995 to avoid reinfection from microbial reservoirs, and this approach still shows promise. Thus, bacteria remain the primary pathogenic factor causing periodontal disease. Therefore, the use of antimicrobial therapy in conjunction with mechanical therapy offers good biological rationale for the treatment of periodontal disease. In later, more advanced stages of periodontal disease involving deeper pockets, clinicians need to be aware of different treatment strategies and various approaches, including mechanical therapy and surgical intervention, possibly including the use of pharmacological agents. Pharmacological therapy, specifically used for better management of periodontitis, includes antimicrobial agents that sufficiently alter the microbiota, combined with host modulators that modulate host responses, such as reducing excessive levels of destructive enzymes, cytokines, prostaglandins, and osteoclast activity. Therefore, clinicians utilizing non-surgical approaches should have a good understanding of different techniques of soft tissue management and reassessment of non-surgical therapy endpoints, and preparation and timing of periodontal surgical intervention, which may include, for example, tissue reattachment, reshaping, and regenerative techniques. Other surgical techniques address and aid in managing apical migration of the periodontal attachment apparatus from gingival recession and other mucogingival pathologies and may include frenectomy, free gingiva, pedicle, and connective tissue grafts, among other techniques too numerous to mention here.

[0015] As can be understood, periodontal pockets are only one of many symptoms of periodontal disease, which involve bacterially induced inflammation. Bacterial-induced inflammation can also occur with mechanical injuries, such as toothbrushing injuries; traumatic injuries, such as thermal, viral, and chemical injuries; iatrogenic injuries, such as the results of some orthodontic treatments; and developmental abnormalities that need to be addressed and treated. These injuries can cause periodontal attachment loss, including clinical signs of bone loss from gingival recession and root exposure; root caries due to gingival recession, and periodontal attachment loss, along with thermal and mechanical sensitivity of the root, can be significant.

[0016] Periodontitis is an inflammatory disease primarily caused by periodontal plaque bacteria, although the host immune response also plays an important role. With the emergence of the concept of systemic antibiotic delivery, solutions have emerged to include intrapocket devices for the treatment of periodontitis, for a more physiologically acceptable and commercially viable drug delivery system as an adjunct to conventional surgical and non-surgical treatments for periodontal infections.

[0017] For example, U.S. Patent No. 8,956,161, entitled "Articles and Methods for Controlling Oral-Derived Systemic Diseases," which is incorporated herein by reference in its entirety, describes a method for treating periodontitis by administering 1.7% hydrogen peroxide gel using a Perio-Tray®, and indicates that while oral rinses and gels can treat gum disease, rinses, brushing, and flossing cannot effectively treat periodontal pockets without a specialized delivery tray because "they typically do not penetrate more than 3 mm into the periodontal pocket" and "application of medications to the periodontal pocket fails to maintain a modified environment sufficient for health and healing." The adjunctive use of 1.7% hydrogen peroxide gel administered topically using prescription customized trays over a three-month period in the treatment of subjects with moderate to severe periodontitis demonstrated statistically significant clinical improvements in pocket depth and bleeding when compared to scaling and root planing alone. Putt MS, Proskin HM.Custom tray application of peroxide gel as an adjunct to scaling and root planning in the treatment of periodontitis: a randomized, controlled three-month clinical trial.J Clin Dent.2012; 23(2):48-56.PubMed. PMID: 22779217.

[0018] A recent systematic and extensive review article was recently published on the current published literature with a meta-analysis on the non-surgical treatment of chronic periodontitis with adjunctive scaling and root planing, with or without adjunctive treatment, based on an extensive search of PubMed / MEDLINE and Embase for randomized controlled trials of scaling and root planing with or without adjunctive treatment, with clinical attachment level (CAL) results for studies of at least 6 months duration, by the ADA Center for Evidence-Based Dentistry in July 2015. The review's conclusions of 72 articles confirmed the scarcity of randomized controlled trials of SRP versus no treatment or debridement, but confirmed the commonly reported result of approximately 0.5 mm improvement in CAL (clinical attachment level). The literature on adjunctive therapies to date is mixed and provides only a moderate level of certainty regarding the benefits of four systemic adjunctive therapies: subdose doxycycline with systemic antimicrobials, systemic antimicrobials, chlorhexidine tips, and photodynamic therapy with diode lasers. There was low level of certainty regarding the benefit of all other adjunctive therapies.

[0019] The following nine paragraphs are excerpted from Riggs, Chad, "Effect of Chemical Pocket Disinfection as an Adjunct to Non-Surgical Maintenance Therapy of Inflamed Periodontal Pockets" (2015). Theses & Dissertations.5, https: / / digitalcommons.unmc.edu / etd / 5 (see pages 4-8 therein).

[0020] Chemical Pocket Disinfection / Chemical Curettage History and Discovery: The development of chemical pocket disinfection began with a procedure called "gingival curettage." The stated purpose of curettage is to remove the sulcular epithelium and any chronically inflamed tissue in the pocket wall, which in theory would promote pocket contraction and new junctional epithelium or connective tissue attachment to the tooth.

[0021] Curettage is accomplished by using mechanical instruments such as curettes (Hirschfeld 1952) or ultrasonic curettes (Goldman 1960, Nadler 1962) along the pocket walls and is often performed in conjunction with scaling and root planing. However, except for surgical removal through incisions (Yukna 1976), gingival curettage frequently results in incomplete removal of pocket epithelium (Stone et al. 1966, Waerhaug 1955, Vieira et al. 1982). To address the drawbacks of incomplete epithelial removal, the use of chemical solutions, also known as "chemical curettage," was subsequently investigated. Various solutions (e.g., sodium sulfide, phenol camphor, antiformin, sodium hypochlorite) were investigated for this purpose (Miller & Sorrin 1927, Waerhaug & Loe 1958); however, only studies using sodium hypochlorite were included in this review. In the early literature, the general term "antiformin" was commonly used to describe various mixtures of sodium hypochlorite solutions and could be read interchangeably with the term "sodium hypochlorite."

[0022] Chemical curettage was introduced as an adjunct to periodontal therapy in the early 1900s (Hecker 1913), where solutions (e.g., sodium hypochlorite / antiformin) removed pocket epithelium through tissue necrosis. In the 1950s, a group of Canadian clinicians published a descriptive technique using chemicals to facilitate periodontal curettage (Box 1952, Box 1953, Shaw 1953). Their anecdotal findings claimed that chemical curettage was safe, rapid, and provided predictable removal of all epithelium from the pocket. They further claimed that chemical removal of soft tissue was limited to the epithelium, but later studies found that the chemical action could extend further into connective tissue (Glickman & Patur 1955, Hunter 1955, Johnson & Waerhaug 1956). As a result, most clinicians stopped using this therapy due to its potential for uncontrollable invasiveness. A later study by Kalkwarf et al. (1982) showed that with a strict protocol, chemical action could be predictably limited, resulting in normal healing. The appropriate time for chemical application was determined in this study to be 1 minute, followed by neutralization and subsequent removal of debris with six curette strokes. Historical evidence of complete removal of pocket epithelium with normal healing was demonstrated with this protocol.

[0023] The immediate effect of chemical curettage consists of complete necrosis of the epithelial and superficial layers of connective tissue, forming a necrotic layer. Greater levels of inflammation result in a more chemolytic effect and less uniform tissue necrosis (Kalkwarf, et al., 1982). In a monkey study observing histological healing after application of sodium hypochlorite, the majority of the necrotic layer was removed by the host's normal inflammatory response after 16 hours, the epithelial lining was reformed after 3 days, and nearly complete healing was achieved after 11 days without any signs of irreparable damage (Johnson & Waerhaug 1956). In a human observation of healing after sodium hypochlorite delivery, the necrotic layer was removed by the host's normal inflammatory response, the epithelial lining was restored after 7 days, and ongoing fibroblast proliferation with continued maturation of connective tissue fibers was observed after 14 days (Kalkwarf, et al., 1982).

[0024] Histological studies of healing for chemical curettage are limited; therefore, the following comments are from studies observing mechanical curettage, which is used to describe the remaining healing, given the great similarities of the therapies. Healing begins soon after curettage with the formation of a blood clot in the pocket. Dilated blood vessels are present in the tissue, and many neutrophils migrate to the wound surface. Granulation tissue rapidly proliferates. After 2 to 5 days, the number of neutrophils decreases unless a bacterial plaque is present and lymphocytes and plasma cells appear. Remodeling and epithelialization of the sulcus occur in 2 to 7 days. Restoration of the junctional epithelium occurs in as little as 5 days. As the granulation tissue matures, immature collagen fibers appear within 21 days, accompanied by a decrease in the number of small blood vessels (Moskow 1964, Stone, et al., 1966).

[0025] Healing after chemical and mechanical curettage appears harmless, but does the healing fulfill its purpose of promoting new connective tissue attachment? Other studies have examined the histological healing of gingival curettage and found no new connective tissue attachment, thus defeating the primary goal of removing inflamed epithelium and replacing it with connective tissue attachment. In a beagle dog study, scaling and root planing with a sodium hypochlorite-citric acid solution was applied to periodontal pockets induced by ligature and compared with scaling and root planing with mechanical soft-tissue curettage. No difference in long junctional epithelial healing was observed between mechanical and chemical curettage (Vieira, et al., 1982). Similar healing was observed in a rhesus monkey study employing scaling and root planing with mechanical curettage (Caton & Zander 1979, Caton, et al., 1980) and another rhesus monkey study employing complete epithelial removal by surgical incision (Yukna 1976). A "window" of connective tissue attachment that interfered with long junctional epithelium was noted in one of these studies (Caton & Zander 1979). A similar long junctional epithelium formed in a study employing subgingival plaque removal without any intentional curettage (Waerhaug 1978). It is generally accepted that curettage heals with a long junctional epithelium similar to the healing achieved with scaling and root planing.

[0026] Chemical curettage has been shown to eliminate bacterial loads in pockets. A study by Adcock et al. (1983) demonstrated that chemical curettage indeed has a bactericidal effect and can effectively eliminate bacteria from deep periodontal pockets. Without any scaling or root planing, sodium hypochlorite solution was applied to the periodontal pockets of patients under the age of 18 with aggressive periodontitis. The results of the study were solely attributable to the bactericidal effect of the solution. A significant reduction in the number of gram-negative anaerobic bacteria and spirochetes was observed, which lasted for 30 to 90 days.

[0027] Scaling and root planing alone has also been shown to reduce pocket bacterial loads by 10- to 100-fold. Significant reductions in gram-negative anaerobic bacteria and spirochetes were observed, with a 1- to 6-month time period required for these organisms to repopulate to baseline levels (Slots, et al., 1979). Combining scaling and root planing with adjunctive chemical curettage would logically be expected to result in improved microbiological and even clinical outcomes; however, a study by Forgas & Gound (1987) demonstrated otherwise. Scaling and root planing alone was compared with scaling and root planing with adjunctive chemical curettage using sodium hypochlorite. The proportions of spirochetes and motile rods in subgingival plaque were monitored. Similar reductions were observed after therapy, with a gradual return to baseline levels after 12 weeks. There were no differences between treatments at any time point.

[0028] Not all patients respond to scaling and root planing with a reduction in periodontal pathogens. Antibiotics may be necessary to enhance disruption of the bacterial flora in the subgingival plaque of the periodontal pocket. In a study observing microbial responses to scaling and root planing, results in two of six patients showed only a slight shift in the bacterial flora after two rounds of mechanical instrumentation. Significant shift and reduction in the bacterial flora was achieved only after systemic administration of tetracycline (Slots, et al., 1979). Chemical curettage should be investigated as it may enhance antimicrobial reduction in patients with sites unresponsive to conventional periodontal therapy. Summary of the Invention

[0029] The ultimate goal of periodontal therapy is to preserve or maintain a healthy and comfortable dentition throughout an individual's lifespan. Ideally, periodontal therapy should resolve inflammation, halt the progression of periodontal disease, improve appearance, and create an environment conducive to the maintenance of health. There is an increasing need for effective prevention, control, and treatment of periodontal disease and preventative maintenance. Patients should be considered co-caregivers, valuing their ability to play a more active role in self-care rather than always relying on clinicians. The prevalence of periodontal attachment loss increases with age: 50 percent in 18-19 year olds; approximately 80 percent in 35-39 year olds; 87 percent in 45-49 year olds; and over 90 percent in those 60 years and older. Most cases can be successfully treated with non-surgical periodontal therapy (Phase I and Phase III). Due to early detection, the majority of periodontal treatment needs should be addressed by treating gingivitis and early periodontitis, preventing disease progression, and maintaining periodontal health followed by active periodontal therapy. Therapeutic scaling and root planing are performed to treat various levels of established periodontal disease found throughout an individual's dentition, and treatment decisions should be site-specific for each tooth.

[0030] In embodiments, the present disclosure provides a pharmaceutical formulation for topical dental administration comprising at least one of: an antimicrobial compound in an effective amount of 5-90% by weight of the total weight of the formulation; at least one peroxide source compound in an effective amount of 1.5-44% by weight of the total weight of the formulation; and at least one gel agent in an effective amount of 1.0-90% by weight of the total weight of the formulation.

[0031] In embodiments, the present disclosure provides a method of treating or preventing at least one of bleeding; swelling; pain; gum recession; tooth-supporting bone recession; tooth-supporting bone loss; or a combination thereof in a subject's oral cavity, the method comprising applying or contacting a topical dental pharmaceutical formulation of at least one of the disclosed formulations to the teeth, gums, or both of the subject's oral cavity.

[0032] In an embodiment, the present disclosure provides a method of treating oral anatomical structures comprising administering to a patient in need of such administration an effective amount of a topical dental pharmaceutical formulation comprising: at least one antimicrobial compound in an effective amount of 5-90% by weight of the total weight of the formulation; at least one peroxide source compound in an effective amount of 1.5-44% by weight of the total weight of the formulation; and at least one gel agent in an effective amount of 1.0-90% by weight of the total weight of the formulation, wherein at least one symptom is minimized or eliminated compared to the patient without administration of the topical dental pharmaceutical formulation, the symptom being selected from: the patient's bleeding gums; the patient's swelling of the gums; the patient's experiencing pain in the gums or teeth; the patient's gum recession; the patient's tooth-supporting bone recession; the patient's loss of tooth-supporting bone mass; or a combination thereof.

[0033] According to at least one of various embodiments, a method of medical treatment is disclosed that includes administering to a wound or diseased area of ​​a subject one or both of a gel solution comprising a clinically effective amount of a peroxide and a viscous antimicrobial agent, the gel solution comprising a clinically effective amount of a topical antibacterial agent, a topical antiviral agent, a topical antibiotic agent, a topical antifungal agent, a topical antiseptic agent, a topical antimicrobial interaction agent, or any combination thereof, wherein the peroxide, when applied, chemically debridements the treatment area relative to the treatment area.

[0034] According to at least one of various embodiments, a method for treating periodontal disease is disclosed, comprising administering to a subject's periodontal pocket in conjunction with mechanical debridement therapy one or both of a gel solution containing a clinically effective amount of a peroxide and a viscous antimicrobial agent, the gel solution containing a clinically effective amount of a topical antibacterial agent, a topical antiviral agent, a topical antibiotic, a topical antifungal agent, a topical antiseptic, a topical antimicrobial interaction agent, or any combination thereof, wherein the peroxide, when applied, chemically debrides and anesthetizes the relevant treatment area of ​​the periodontal pocket. In at least one of various embodiments, the gel solution may include at least 10% urea peroxide.

[0035] In at least one of various embodiments, the viscous antimicrobial agent is selected from the group consisting of tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, and metronidazole. , ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin.

[0036] A broad definition of mechanical debridement can include tools and devices beyond manual instrumentation, involving dental scalers and curettes, such as sonic and ultrasonic scalers, lasers and other devices that can modify the surface physical properties of both organic and inorganic implants, bone, tissue, and root surfaces for optimized and controlled surface finishes. Instrument blades and other functional cutting edges can include any cutting edge or working edge, for example, sonic or ultrasonic tips, or laser tips.

[0037] In at least one of various embodiments, the gel solution, the viscous antimicrobial agent, or both may be applied to a subject in a pocket depth of 5 millimeters or greater in conjunction with a non-surgical mechanical debridement periodontal disease treatment. In at least one of various embodiments, the periodontal pocket depth may be at least 7 millimeters. In at least one of various embodiments, the periodontal pocket depth may be at least 10 millimeters.

[0038] In at least one of various embodiments, a 10% urea peroxide gel solution may be used as an anesthetic in an amount effective to eliminate the need for a separate anesthetic.

[0039] In at least one of various embodiments, the viscous antimicrobial agent can be tetracycline powder, where the tetracycline powder becomes viscous when administered.

[0040] In at least one of various embodiments, the viscous antimicrobial agent is a powdered form of tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, or the like. The powder formulation may be ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin, where the powder form becomes viscous when administered.

[0041] In at least one of various embodiments, the viscous antimicrobial agent can be a powder form of a topical antibacterial agent, a topical antiviral agent, a topical antibiotic agent, a topical antifungal agent, a topical disinfectant agent, and a topical antimicrobial interaction agent, wherein the powder form becomes viscous when administered.

[0042] In at least another embodiment, the viscous antimicrobial agent can be a combination of at least two of a topical antibacterial agent, a topical antiviral agent, a topical antibiotic agent, a topical antifungal agent, a topical disinfectant, and a topical antimicrobial interaction agent in powder form, wherein the powder form becomes viscous when administered.

[0043] In at least another embodiment, the viscous antimicrobial agent can be a combination of at least three of a topical antibacterial agent, a topical antiviral agent, a topical antibiotic agent, a topical antifungal agent, a topical disinfectant agent, and a topical antimicrobial interaction agent in powder form.

[0044] In at least one of various embodiments, the topical antiseptic can be povidone-iodine, stannous fluoride (stannous fluoride), hydrogen peroxide, or chlorhexidine.

[0045] In at least one of various embodiments, the antifungal agent can be nystatin, mycelex, fluconazole, ketoconazole, posaconazole, or clotrimazole.

[0046] In at least one of various embodiments, the method may further include: sharpening or finishing the dental or medical instrument working surface with a finishing tool; and performing mechanical debridement using the sharpened or finished instrument. The finishing tool may be configured to create an optimized working surface of the blade, whereby the mechanical debridement treatment is performed on the optimized working surface. The sharpening tool may be configured to create the optimized working surface, including at least one of an absence of wire edges and a surface sharpened to 1-5 microns.

[0047] In at least one of various embodiments, the method may further include: sharpening or finishing the dental instrument working surface with a finishing tool; and performing an optimized surface finish for the dental implant with the sharpening or finishing dental instrument. The finishing tool is configured to create an optimized working surface of a cutting edge or functional edge, whereby the implant surface finishing treatment is performed on the optimized working surface. The finishing tool may be configured to create an optimized working surface for the instrument, including, for example, no wire edges, no deformations, and / or a working surface that is finished to the tolerances of the implant.

[0048] In embodiments, tools are provided with optimized working surfaces that can create controlled finished surfaces for implants in vivo. For example, finishing tools can be configured to retap or reshape the body of an implant. Finishing and shaping working surfaces can include surfaces for taps, tap dies, plasma spraying, burnishing, and thread cleaning. In embodiments, thread sharpening or shaping tools can be configured to be attached to implant drills or implant removal wrenches, or other devices for in vivo use.

[0049] In various embodiments, instruments are finished to a controlled surface finish that is optimal for the instrument's use. For example, instruments for finishing bone for bone grafting may be finished to a roughness (e.g., on the order of hundreds of microns) that promotes successful implantation due to osteoblast activity or bone cells responding to increased bone roughness. In another example, finishing tools may be configured to create a smoother finish, e.g., 1-99 microns, to create an implant surface that should be biologically clean. The finish may allow for placement of a sprayed or applied root conditioner.

[0050] As described herein, finishing tools can be used to create an optimized working surface for any manufactured appliance metal alloy, ceramic, or plastic.

[0051] In at least one of various embodiments, the method may include sharpening the dental blade with a sharpening tool configured to create a cutting edge that optimizes the working surface of the blade, for example, by optimizing the rake angle, so that the mechanical debridement treatment is performed with the optimized blade.

[0052] In at least one of various embodiments, the method may include instructing the subject or the subject's caretaker to floss the subject with a gel solution containing urea peroxide at least once daily during the active phase of periodontal disease. In at least one of various embodiments, the method may include instructing the subject or the subject's caretaker to brush the subject's gums with a gel solution containing 10% urea peroxide at least once daily after treatment during the active phase of periodontal disease. In at least one of various embodiments, the method may include instructing the subject or the subject's caretaker to regularly floss or clean the subject with a dental cleaning device having a solution containing 10% urea peroxide at least once daily during the maintenance phase of periodontal disease as part of the subject's regular dental care routine after treatment. The dental cleaning device may be selected from the group consisting of a brush, an applicator, and an interdental cleaner. In at least one of various embodiments, the interdental cleaning device may be selected from the group consisting of a floss, a pick, or an interdental brush. In at least one of various embodiments, the interdental cleaning device is a superfloss comprising a sponge provided with at least 10% urea peroxide, for example, a sponge impregnated or coated with at least 10% urea peroxide.

[0053] In at least one of various embodiments, the method may comprise administering a first application of a viscous antimicrobial agent prior to applying the first application of the gel solution.

[0054] In at least one of various embodiments, the method may include administering a viscous antimicrobial agent, a gel solution, or both multiple times during the active phase of the disease. In at least one of various embodiments, the method may include administering a gel solution to the periodontal pockets of the subject, and applying a follow-up treatment comprising administering an antimicrobial agent to the periodontal pockets of the subject.

[0055] In at least one of various embodiments, the method comprises administering to a treatment area of ​​a subject in conjunction with a mechanical dental care treatment a gel solution comprising a clinically effective amount of peroxide, wherein the peroxide solution chemically debridements and anesthetizes the treatment area; and administering to a subject a gel solution comprising at least one of the following: tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, a combination of amoxicillin and clavulanic acid, metronidazole, gemifloxacin, levofloxacin, levofloxacin, tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, a combination of amoxicillin and clavulanic acid, metronidazole, gemifloxacin, levofloxacin, tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindam and / or a topical antiseptic; a topical antifungal; or a topical antimicrobial-antimicrobial interaction agent, the topical antiseptic comprising at least one, or in other embodiments at least two, or in still other embodiments at least three of: ciprofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin, and derivatives thereof, and / or a topical antimicrobial-antimicrobial interaction agent.

[0056] In at least one of various embodiments, the gel solution can include at least 10% urea peroxide. In at least one of various embodiments, the viscous antimicrobial agent is selected from the group consisting of tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, and combinations of amoxicillin and clavulanic acid. , clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, ciprofloxacin, and derivatives thereof.

[0057] In at least one of various embodiments, the viscous antimicrobial agent consists essentially of minocycline, metronidazole, and ciprofloxacin in a calcium hydroxide paste.

[0058] In at least one of various embodiments, the viscous antimicrobial agent consists essentially of minocycline, metronidazole, and ciprofloxacin in a calcium hydroxide paste at between 0.5 and 1.5 mg / mL, preferably about 1 mg / mL. As used in this paragraph, "about" means plus or minus 8%, more preferably plus or minus 5%, and most preferably plus or minus 2%.

[0059] In at least one of various embodiments, the viscous antimicrobial agent further consists essentially of an antimicrobial agent, hi at least one preferred embodiment, the antimicrobial agent is chlorhexidine gluconate.

[0060] In at least one of various embodiments, the dental care treatment may include a treatment selected from root treatment for bone grafting, treatment or prevention of peri-implantitis, dental surgical tissue graft treatment, and treatment of a subject's natural tooth root. Other therapeutic uses include treatment of edentulous ridges for surgical augmentation gratings, maxillary sinus lift surgery, tooth extraction sockets (implant-related or not), and other dental and other oral surgery-related procedures.

[0061] In at least one of various embodiments, dental implant treatment can include treatment or prevention of peri-implant mucositis and peri-implantitis resulting from titanium implants or implants made from other materials.

[0062] In at least one of various embodiments, the medical treatment may include a medical implant other than a dental treatment. In at least one of various embodiments, the medical treatment may include a surgical treatment selected from treating a bone surface for bone grafting, treating a tissue area for tissue grafting, treating the surface of an implant, and treating an implant site in a subject, where the wound site comprises a surgical wound. In embodiments, the medical care treatment may include treating or preventing osteolysis, implantitis, or implant rejection due to a non-organic implant. In embodiments, the surgical treatment may include implant surgery, including, for example, implant surgery for a prosthetic joint, a prosthetic heart valve, a cardiac pacemaker, and a catheter.

[0063] In at least one of various embodiments, the dental care treatment can include treating the root of the subject's tooth by root planing or chemical root preparation, or both. In at least one of various embodiments, treating the root of the subject's tooth includes treating a root canal, apical, intradental, periodontal lesion, for example, during an apicoectomy.

[0064] In at least one of various embodiments, the dental care treatment method may include administering a gel solution to a treatment area of ​​the subject; and applying a follow-up treatment including administering a viscous antimicrobial agent to the treatment area of ​​the subject.

[0065] In at least one of various embodiments, the method may further include: sharpening or finishing the dental or medical instrument working surface with a finishing tool; and performing a mechanical medical care treatment using the sharpened or finished dental or medical instrument. The finishing tool may be configured to create an optimized working surface for the blade, whereby the mechanical dental care treatment is performed on the optimized working surface. The sharpening tool may be configured to create an optimized working surface including at least one of: no wire edges, no deformation, a surface sharpened from 1-5 microns, or producing an optimized, controlled roughness or smoothness for better tissue repair or cell growth, or allowing for better controlled surface roughness for "bonding agent" adhesion and further chemical treatments that require controlled surface pre-roughness at a set micron level.

[0066] In at least one of various embodiments, the present disclosure provides a viscous pharmaceutical composition comprising a first component comprising at least about 10% by weight of urea peroxide as an active ingredient, and a second component comprising an antimicrobial agent. In embodiments, the second component can consist essentially of at least one, or in other embodiments, at least two, or in still other embodiments, at least three of a topical antibacterial agent, a topical antiviral agent, a topical antibiotic agent, a topical antifungal agent, a topical disinfectant agent, and a topical antimicrobial interaction agent.

[0067] In at least one of various embodiments, the viscous pharmaceutical is a gel composition. In at least one of various embodiments, the solution may comprise: a pharmaceutical comprising a weight percent of a first component effective to chemically debride a treatment area for dental treatment. In at least one of various embodiments, a partial percentage of an antimicrobial agent consisting essentially of at least one, or in other embodiments at least two, or in yet other embodiments at least three, of a topical antibacterial agent, a topical antiviral agent, a topical antibiotic agent, a topical antifungal agent, a topical antiseptic agent, and a topical antimicrobial interaction agent is the remainder of the solution.

[0068] In at least one of various embodiments, the present disclosure provides a viscous pharmaceutical composition comprising a first component comprising at least about 10% by weight of urea peroxide as an active ingredient; and a second component comprising an antimicrobial agent. In embodiments, the second component is selected from the group consisting of tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, and the like. In another embodiment, the anti-inflammatory drug may consist essentially of at least one, or in another embodiment at least two, or in yet another embodiment at least three of: cephalosporin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, minocycline, metronidazole, ciprofloxacin, and combinations of derivatives thereof.

[0069] In at least one of various embodiments, the viscous medication is a gel composition. In at least one of various embodiments, the solution may comprise a medication comprising: a weight percent of a first component effective to chemically debride a treatment area for dental treatment. In at least one of various embodiments, the first component may be selected from the group consisting of tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, cefotaxime ... A partial percentage of the antimicrobial agent consisting essentially of at least one, or in other embodiments at least two, or in still other embodiments at least three of: fluoxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and derivatives thereof, is the remainder of the solution.

[0070] In at least one of various embodiments, a dental product is described that includes a dental cleaning device coated, impregnated, or provided with a solution containing at least 10% urea peroxide. The dental cleaning device can be selected from the group consisting of a brush and an interdental cleaner. In at least one of various embodiments, the interdental cleaning device can be selected from the group consisting of a floss, a pick, or an interdental brush. In at least one of various embodiments, the interdental cleaning device is a superfloss that includes a sponge provided with at least 10% urea peroxide.

[0071] In at least one of various embodiments, the peroxide gel and one or more of the following are selected from the group consisting of tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, metronidazole A method for treating periodontal disease is described, comprising administering a gel solution containing a viscous antimicrobial agent containing a clinically effective amount of one or more of the following combinations of amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and combinations of minocycline, metronidazole, ciprofloxacin, and their derivatives to a subject's periodontal pocket using a periodontal probe or other dental instrument to chemically debride and curette the treatment area; and, during the active period of chemical debridement, non-surgically scaling and root planing the treatment area using a periodontal scaler or curette. The periodontal pocket to be treated may be at least 5 mm thick.

[0072] In at least one of various embodiments, a method for treating periodontal disease is described, comprising administering a gel solution containing a viscous antimicrobial agent, including a peroxide gel and a clinically effective amount of an antimicrobial agent, such as a topical antibacterial agent, a topical antiviral agent, a topical antibiotic, a topical antifungal agent, a topical antiseptic agent, and a topical antimicrobial interaction agent, to a subject's periodontal pocket using a periodontal probe or other dental instrument to chemically debride and curette the treatment area; and, during the active period of chemical debridement, non-surgically scaling and root planing the treatment area using a periodontal scaler or curette. The treated periodontal pocket can be at least 5 mm thick.

[0073] The method may further comprise: sharpening or finishing the dental instrument working surface with a finishing tool configured to create an optimized working surface of the blade, whereby the root planing treatment is enhanced root planing, wherein the optimized working surface comprises at least one of an absence of a wire edge and a surface sharpened from 1-5 microns.

[0074] As used herein, "treating" or "treatment" refers to preventing or reducing the severity of the symptoms or effects of a disorder or disease, as well as therapeutic measures therefor.

[0075] A "subject" according to the present invention refers to any multicellular organism that has skin.

[0076] Typically, the subject is a mammal such as a mouse, rat, pig, horse, cat, dog, elephant, giraffe, monkey, or human and the like. Typically, the mammal is a human.

[0077] The term "administration" as used herein refers to any method of delivering a composition to a subject in a manner that is effective in treating dental conditions or disorders, such as peri-implant mucositis (without bone loss) and peri-implantitis (with bone loss), in a manner consistent with sound medical practice. The compositions are preferably administered such that they cover the entire area to be treated.

[0078] As used herein, the phrase "safe and effective amount" refers to an amount of a composition or its components that is high enough to positively correct the disorder being treated, but low enough to avoid serious side effects, within the bounds of sound medical advice. A safe and effective amount will vary depending on the particular disorder or disorders being treated, the severity of the disorder, the duration of treatment, the specific components of the composition being used, and similar factors, as known to healthcare providers, including physicians and veterinarians. In embodiments, the disclosed pharmaceutical formulations may be approved by physician prescription or over-the-counter (OTC) for administration as a treatment or combination therapy by a healthcare provider or self-administered.

[0079] As used herein, the term "augmented root planing" refers to a therapeutic procedure that uses sharpening and shaping tools designed to remove rough, calculus-infiltrated, or toxin- or microbial-contaminated cementum or superficial dentin and / or to achieve a desired surface finish and profile. Augmented root planing involves the use of a variety of mechanically designed instruments to impart a desired, controlled surface roughness and geometry to teeth, dental implants, which can be employed for the application of antimicrobial agents and / or microbial chemical mediators and other chemical root conditioners. In embodiments, tool shaping and sharpening may be performed in conjunction with each treatment using optimized sharpening tool techniques described in U.S. Patent Nos. 6,074,293, 6,361,408, 6,949,018, U.S. Patent Application No. 15 / 241,252, and International Patent Application No. PCT / US2015 / 041998, each of which is incorporated by reference herein in its entirety (e.g., Honing Channel® Sharpening System).

[0080] In particular, the enhanced root planing described herein is a process for removing residual embedded calculus and diseased root cementum from tooth surfaces to create a smooth, hard, biologically clean surface. This helps allow the patient's oral tissues, i.e., periodontal (gum) tissue and supporting bone, to repair and regenerate on the root surfaces of the dentition. Disclosed herein are embodiments for enhanced root planing using dental instruments with sophisticated, functionally optimized working surfaces. For example, described herein are dental instruments with smooth and sharp cutting edges specifically configured for dental procedures to create root surface smoothness as close as possible. To help minimize bacterial growth and prevent microbial regrowth on the roots, the root surface smoothness should resemble white tooth enamel, kitchen glass, or other smooth surfaces, if possible. The smoothness of the root surface is tested by a clinician using specialized instruments after treatment.

[0081] In embodiments, enhanced root planing also includes the use of viscochemical and antimicrobial agents, such as peroxide gel solutions, which chemically debride the treated area of ​​periodontal tissue; and other antimicrobial agents, such as tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, combinations of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, methadone ... In some embodiments, the term "antibiotics" may refer to a therapeutic treatment that includes mechanical root planing in conjunction with chemical debridement using a viscous antimicrobial agent that includes a clinically effective amount of an antibiotic such as dazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin.Viscous chemical treatments include those that are provided in a viscous form, such as peroxide gel containing 10% urea peroxide, or chemical treatments that become viscous when administered for treatment, such as tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, and the like, which form a paste when administered by mixing with gingival crevicular fluid or another treatment (e.g., peroxide gel). Powder forms of isopropyl azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin.

[0082] In embodiments, enhanced root planing can also refer to a therapeutic procedure that includes mechanical root planing in conjunction with chemical debridement using a viscous chemical treatment and an antimicrobial agent, such as a peroxide gel solution that chemically debride the treated area of ​​periodontal tissue; and a viscous antimicrobial agent containing a clinically effective amount of a topical antibacterial agent, antiviral agent, antibiotic agent, antifungal agent, antiseptic, or antimicrobial interaction agent. Viscous chemical treatments can include those provided in a viscous form, such as a peroxide gel containing 10% urea peroxide, or a chemical treatment that becomes viscous when administered for treatment, such as a powder form of a topical antibacterial agent, antiviral agent, antibiotic agent, antifungal agent, antiseptic, or antimicrobial interaction agent that forms a paste when administered by mixing with gingival crevicular fluid or another treatment (e.g., peroxide gel).

[0083] The "enhanced" mechanical planing and controlled surface finishing described herein also includes controlled finishing for tools and other biological and implant surfaces, such as tooth root surfaces, bone surfaces, tissue surfaces, or implant surfaces, using medical instruments with optimized working surfaces, such that mechanical medical care treatments are performed using optimized working surfaces, as also described above for "enhanced root planing." [Brief explanation of the drawings]

[0084] Embodiments are illustrated in the figures of the accompanying drawings, which are intended to be illustrative and not limiting, and like reference symbols are intended to refer to like or corresponding items.

[0085] [Figure 1A] 1 illustrates a cross section of a tooth in healthy periodontium. [Figure 1B] 1 illustrates a cross section of a tooth in healthy periodontium.

[0086] [Figure 2] 1 illustrates a cross section of a tooth in periodontium with gum disease.

[0087] [Figure 3A] 1 shows teeth and periodontal tissues in advanced stages of periodontitis. [Figure 3B] 1 shows teeth and periodontal tissues in advanced stages of periodontitis. [Figure 3C] 1 shows teeth and periodontal tissues in advanced stages of periodontitis.

[0088] [Figure 4A] 1 shows an image of a patient's teeth and gums at the start of treatment with the disclosed oral dental preparation. [Figure 4B] 1 shows an image of a patient's teeth and gums after treatment with the disclosed oral dental preparation.

[0089] [Figure 5A]1 shows images of exemplary comparative x-ray images of a patient's teeth and gums prior to treatment with the disclosed oral dental preparation. [Figure 5B] 1 shows images of exemplary comparative x-ray images of a patient's teeth and gums after treatment with the disclosed oral dental preparations. DETAILED DESCRIPTION OF THE INVENTION

[0090] Gum health is affected by many local factors. Some specific local factors are bacterial plaque and tartar. These local factors contribute, in part, to the inflammatory response of the gums. Proper oral hygiene can control many of these local factors, so that the disease process never begins or, if it does begin, is reversed. However, untreated gingivitis can lead to periodontitis.

[0091] Periodontitis is a severe infection of the gums that destroys the gum tissue and bone that support the teeth. In people with periodontitis, the gum lining and bone separate from the teeth, forming pockets. These pockets between the teeth and gums continue to collect toxic substances and debris resulting from bacterial proliferation, maturation, and infection. The body's immune system fights the bacteria as plaque spreads and grows below the gum line. Toxins or poisons produced by the bacteria in the plaque biofilm and enzymes produced by the body's natural immune response to fight infection break down the bone and connective tissue that holds the teeth in place. As the disease progresses, the pockets deepen and more gum tissue and bone are destroyed. When this occurs, the teeth are no longer anchored in place and become loose, resulting in tooth loss. Periodontitis also disrupts the balance of healthy bacteria and T cells, disrupting collagen production for connective tissue and destroying the pocket walls. Periodontitis is also associated with an increased risk of heart attack, stroke, and other serious health problems.

[0092] Periodontitis is divided into different classes: chronic periodontitis and aggressive periodontitis. Chronic periodontitis is the most common and occurs mostly in adults with progressive severity over many years, most often showing signs of periodontal attachment loss as early as age 18. Aggressive periodontitis is relatively uncommon and occurs mostly during childhood or adolescence.

[0093] 1A and 1B show a cross section of a tooth 1 in healthy periodontium 17. The crown 8 of each tooth 1 has a coating of enamel 2 that protects the underlying dentin 3. Enamel is the hardest substance in the human body, even harder than bone. It derives its hardness from rows of tightly packed calcium and phosphorus crystals within a protein matrix structure. Once enamel is formed during tooth development, its minerals are rarely replaced during a tooth's lifespan. Mature enamel is not considered "living" tissue. The top of the crown 8 is the cusp 9 of the tooth 1.

[0094] The main internal element of tooth 1, dentin 3, is a bone-like elastic, compressible living tissue that connects to the central nerve within dental pulp 4. The dental pulp includes the canal pulp 5 and the root canal 6, which forms the central cavity of the tooth. The root pulp of the root canal 6 is made up of soft tissue and contains the blood vessels and nerves 25 of the tooth.

[0095] The root 12 is the region of the tooth 1 beneath the gums; the neck 11 is the region separating the crown 8 from the root. Some teeth 1, such as incisors and canines ("eye"), have only one root, while molars and premolars have up to four or more roots per tooth. At the base of the root shaft of a multi-rooted tooth 1 is a furcation 13 where two or more roots meet. The extension of the root pulp 6 within the root 12 of the tooth 1 is called the root canal 6. The root canal 6 connects to the surrounding tissues through the apical foramen 15, an opening at the root tip 14 of the root 12. This is an opening in the cementum 7 through which the blood vessels and nerves 24 of the tooth 1 enter the pulp 4 from the surrounding tissues. The blood vessels supply and circulate blood delivered from the alveolus through channels 27.

[0096] The periodontal tissues 17 refer to the supporting tissues of the teeth and include the alveolar bone 21, gingiva 18, periodontal ligament 22, and the outer layer of the root 12 of the tooth 1, which are covered by a layer of cementum 7. The gingiva 18 is the only clinically visible element of the periodontal tissues 17 in the mouth.

[0097] The periodontal ligament 22 is a group of specialized connective tissue fibers that attach the tooth to the alveolar bone within which it resides. It consists of an extracellular compartment of cells and fibers. The cells are fibroblasts, epithelial cells, undifferentiated mesenchymal cells, and bone and cementum cells. The extracellular compartment consists of type 1, 3, and 5 collagen fiber bundles embedded within the intercellular substance. Periodontal ligament 22 collagen fibers are classified according to their orientation and location along the tooth. The alveolar bone 21 is surrounded, for the most part, by the subepithelial connective tissue 28 of the gingiva 18, which is covered by various characteristic gingival epithelium. The attached gingiva 18 extends from the free gingiva 19 apically and eventually merges with the alveolar mucosa. The attached gingiva 18 is firmly connected to the underlying cementum 7 and alveolar bone 21 by connective tissue collagen fibers. The cementum 7 overlying the root 12 of tooth 1 is attached to the adjacent cortical surface of the alveolar bone 21 by the crestal fibers 30, horizontal fibers 31, and oblique fibers 32 of the periodontal ligament 22. The interdental horizontal fibers 33 extend between adjacent teeth beyond the crest of the alveolar bone 21 and are embedded in the cementum 7 of the adjacent teeth; they form the interdental ligament. The interdental horizontal fibers 33 keep all teeth aligned and can be considered part of the gingival tissue because they have no bony attachment. The periodontal vessels 26 surround the root of the tooth and supply blood from the alveolus through channels 27.

[0098] The interface between tooth 1 and surrounding gingival tissue 19 is a dynamic structure. Gingival tissue forms a gap surrounding tooth 1, similar to a fluid-filled sulcus, in which food debris, endogenous and exogenous cells, and chemicals are suspended. The depth of this gap, known as sulcus 16, is in a constant state of change due to microbial invasion and subsequent immune responses. Gingival sulcus 16 is the space between the tooth 1 surface and the narrow, unattached cervical collar 20 of the free gingiva 19. Deep within sulcus 16 lies an epithelial attachment 29, consisting of approximately 1 mm of junctional epithelium and another 1 mm of gingival fibrous attachment, encompassing the 2 mm biological width naturally found in the oral cavity. Sulcus 16 is the area of ​​separation between the surrounding epithelium and the encompassing tooth 1 surface.

[0099] The free gingiva 19 surrounds the tooth 1, creating a gingival cuff or collar 20 measured from the gingival sulcus 16 of the attached gingiva, which extends approximately 1.5 mm coronally. The gingival sulcus 16 is lined by the sulcular epithelium 29. The sulcular epithelium is the epithelium present on the sulcular side of the edge of the free gingiva 19. The oral epithelium 28 is present on the other side of the edge of the free gingiva 19. It extends from the edge of the free gingiva 19 to the junctional epithelium (averaging a depth of 0.69 mm). The junctional epithelium, or epithelial attachment, is a group of tissues at the apical portion of the gingival sulcus 16 that attaches the gingiva to the tooth. The width of the junctional epithelium averages approximately 1 mm. The medial surface of the free gingiva 19 next to the tooth forms the gingival wall of the sulcus. The depth of a healthy gingival sulcus 16 is approximately 1 to 3 mm in length.

[0100] Gum disease is classified into four stages: stage 1 gingivitis, stage 2 early periodontitis, stage 3 moderate periodontitis, and stage 4 severe periodontitis. Figure 2 shows a cross-section of a tooth 1 in periodontitis-affected periodontium 17. The inner surface of the free gingiva 19 next to the tooth 1, which forms the gingival wall of the sulcus 16, becomes inflamed, swollen, and erodes as it moves away from the tooth, forming a gingival sulcus pocket 36. In stage 1, this phenomenon is called a gingival pocket. The epithelial attachment 29 does not migrate; it simply remains at the same attachment level as found in a healthy state before the onset of disease. The only anatomical landmark that undergoes migration is the gingival margin in a coronal direction. No destruction of connective tissue fibers (gingival fibers) or alveolar bone occurs in the gingival pocket. Histologically, an infiltration of inflammatory cells is expected. A biofilm 35, or plaque, forms on the outer wall of the tooth 1 and penetrates along the cementum 7 into the subgingival region. The biofilm 35 is composed of colonies containing bacteria compatible with the periodontal ecosystem. Pathogenic bacteria can appear within oral biofilms that are not regularly disrupted by traditional oral hygiene procedures such as brushing and flossing. As gum disease progresses, pathogenic bacteria infect the periodontal pockets 36 around the teeth, becoming increasingly difficult to remove. Stage 1 gingivitis involves gingival inflammation but no bone loss. This early sign of oral disease is completely reversible when the etiology of the edematous reaction is resolved and frequently occurs without dental surgery. However, in certain circumstances, limited periodontal surgical procedures are necessary to reduce the depth of the gingival pockets to a healthy 1-3 mm.

[0101] Without regular oral care, most people will develop gingivitis. In those who develop periodontal disease, pathogens such as bacteria in biofilms 35 and enzymes from the body's immune response can progress to periodontitis, leading to tissue erosion, periodontal pocket formation 36, and ultimately destruction of the connective tissue of the alveolar bone 21 and gums 18, which can result in tooth loss 1.

[0102] Figures 3A-3C show three progressive stages of periodontitis. As shown in Figure 3A, stage 2 early periodontitis results in inflammation of the gums and surrounding tissues and initial bone loss. Figure 3B shows stage 3 moderate periodontitis with inflammation of the gums and surrounding tissues, exposing the tooth root 12, and a biofilm 35 forming a tartar 36 around the root 12, resulting in moderate bone loss 21. In stage 4 severe periodontitis, as shown in Figure 3C, gum inflammation is severe and several millimeters of the tooth root are completely exposed. The biofilm tartar penetrates into the root 12, and there is significant loss of alveolar bone 21 and connective gingival tissue. The periodontal ligament 22 undergoes dramatic changes due to chronic periodontal disease, with the deeper structures of the periodontal tissue 17 accompanying periodontitis. The fibers of the periodontal ligament 22 become disorganized and their attachment to either the alveolar bone proper or the cementum through Sharpey's fibers is lost due to resorption of these two hard dental tissues. Sharpey's fibers are the major fiber ends that lie in either the cementum or the alveolar bone 21.

[0103] 4A and 4B show images of the patient's teeth and gums at the start of treatment (4A), with significant bleeding and swollen gums, and an image (4B) after treatment with the oral dental preparation at a later patient appointment (12 days later), when there is no visible bleeding, a significant reduction in swelling is apparent to the dental professional, and the patient is not in pain. No local injectable anesthesia for comfort was needed or requested by the patient during the initial or subsequent periodontal treatment visits for scaling and root planing involving use of the disclosed topically applied dental preparation containing an antimicrobial agent.

[0104] 5A and 5B show exemplary comparative x-ray images of a patient's teeth and gums before (5A) and after (5B) treatment with the disclosed oral dental preparation. FIG. 5A shows a section of the patient's teeth and gums before treatment with the disclosed preparation (i.e., time zero). Aspects and features of note are: deep pockets, gum recession, and eroded tooth-supporting bone density. FIG. 5B shows the same approximate section of the patient's teeth and gums shown in FIG. 5A approximately 22 months after topical treatment with the disclosed oral dental preparation and topical treatment with a growth factor-enhanced matrix (GEM21S®). Aspects and features of note in the post-x-ray image are: restoration or regrowth of eroded tooth-supporting bone density and bone filling. The patient had undergone previous root canal therapy more than 12 months prior, which did not alter the observed aspects and features of the surrounding periodontal tissues and bone density, making it appropriate for the disclosed dental preparation to regenerate periodontal tissues.

[0105] Conventional treatment for periodontitis depends on the severity of the disease. As mentioned above, healthy periodontal tissue exhibits a sulcus approximately 1–3 mm in length and depth. Precise millimeter measurements of sulcus depth are obtained using an instrument known as a periodontal probe. Clinically, a healthy gingival sulcus has a probing depth ranging from approximately 1–3 mm and should not bleed when properly probed. During clinical probing, the periodontal probe usually penetrates slightly into the junctional epithelium. Sulci greater than 3 mm in length usually indicate unhealthy periodontal tissue and are therefore best described using the word "pocket."

[0106] When the original sulcus depth increases and apical migration of the junctional epithelium occurs concomitantly, the pocket is now covered by pocket epithelium (PE) instead of junctional epithelium (GE). A probing measurement of 4 mm or greater must be clinically documented to have a true periodontal pocket. In this condition, most of the gingival fibers that originally attached the gingival tissue to the tooth are destroyed. The depth of the periodontal pocket must be recorded in the patient's record for appropriate monitoring of periodontal disease. The periodontal pocket can become a space for infection, resulting in abscess formation with papules on the gingival surface. Lancetosis and drainage of the abscess and systemic antibiotics may be necessary; placement of a local delivery system within the periodontal pocket to reduce local infection may also be considered.

[0107] As part of an initial full clinical dental comprehensive examination, periodontal probing depths are recorded for each tooth along with all other periodontal parameters. Client assessment, a treatment plan tailored to the entire dentition and each tooth that addresses the client's needs, oral self-care instructions, preventative and non-surgical periodontal therapy, supportive care to maintain health, and re-evaluation are all important components of thorough periodontal care.

[0108] Periodontal health and treatment can continue over the course of many years, and in some cases, regular treatment and maintenance can continue for life. Periodontal therapy is typically divided into three phases: Phase I therapy: a non-surgical phase followed by evaluation of response to the non-surgical phase; Phase II therapy: a surgical phase; and Phase III: a periodontal maintenance phase.

[0109] Phase I therapy, the non-surgical preliminary phase of treatment, includes plaque control and patient education regarding oral care and diet, calculus removal and root planing, correction of factors affecting periodontal health resulting in restoration and prosthetics, pulp therapy if necessary, and caries extraction along with temporary or definitive tooth restoration. The non-surgical phase may also include local and / or systemic therapy, occlusal therapy, mild orthodontic exercises, and temporary splints and dentures. The non-surgical phase is followed up by assessment, particularly checking pocket depth and gingival inflammation as described herein, and rechecking for biofilm, calculus, and caries as part of comprehensive care.

[0110] If Phase I therapy is determined to be ineffective in an area of ​​the mouth's dentition, treatment may progress to Phase II, the surgical phase. Periodontal surgery may be recommended in areas of the mouth that do not respond to non-surgical treatment to create a more permanent, healthier environment around the teeth. Soft tissue plastic or regenerative surgery may be necessary to improve cosmesis and to rebuild and replace lost bone support around the teeth. During periodontal surgery, the physician has the opportunity to visually ensure that all calculus (tartar) on the root surfaces has been thoroughly removed and, more importantly, that adequate root planing has been achieved to provide root surfaces with biologically clean surfaces. Upon completion of corrective periodontal care and specific surgical and therapeutic elements during Phase I and Phase II, and restoration of clinical health throughout the mouth, dental implants, if planned, may be placed in edentulous sites during this phase of treatment. Shallower pockets are easier to maintain for both patients and dental professionals, who regularly and periodically clean their own teeth and treat their own gums.

[0111] Finally, the maintenance phase, Phase III therapy, involves periodic rechecks of the periodontal tissues. This includes checking the condition of the gums for plaque and tartar, pockets and inflammation, occlusion, tooth mobility, and any other pathological changes. For many subjects, gum and periodontal disease should be treated as a chronic condition with lifelong Phase III therapy.

[0112] As can be appreciated, optimal periodontal therapy using Phase I treatment avoids Phase II and can be effective with non-surgical treatment alone in Phase I and with resolution of infection followed by maintenance in Phase III. Non-surgical treatment is best when it completely addresses the cause of gingival and periodontal disease and can completely halt its progression. Mechanical debridement, such as scaling and root planing, is considered a non-surgical treatment. Scaling and root planing is the careful cleaning of the root surface to remove biofilm, i.e., plaque and calculus (tartar), from deep periodontal pockets and to lubricate the root and remove bacterial toxins.

[0113] After scaling and root planing, many patients do not require any further effective treatment, but the majority of patients require ongoing Phase III maintenance therapy to maintain periodontal health, which is a lifelong or lifelong regimen. Traditionally, scaling and root planing is optionally followed by adjunctive therapies such as topical delivery agents, systemic antibiotics, and host modulation. "Host modulation therapy" generally refers to the host's immune response to an antigen or antigens, with the goal of disrupting the immunoinflammatory pathways within the host's response to any pathogen that perpetuates the inflammatory response. More specifically, in the context of periodontal disease, "host modulation therapy" refers to a therapeutic concept in which drug therapy can be used as an adjunct to conventional periodontal treatment to mitigate the destructive aspects of the host's inflammatory response.

[0114] Phase II therapy involves surgery when Phase I treatment is insufficient, for example, when access for scaling and root surface debridement is compromised. Traditionally, Phase II treatment is indicated when, for example, periodontal pockets are 5 mm or larger, root fissures or pits are present, furcation defects are present, or persistent or healing-related infection exists in the periodontal pockets around implants. Periodontal surgery is performed, among other things, to gain access for thorough debridement and root scaling, reduce pocket depth, and restore and improve the symptom, function, and aesthetic appearance of periodontal and surrounding tissues. This includes reconstructing lost structures, optimizing biofilm control, restorative work, and sculpting gingival contours and margins for implants. When surgical intervention is necessary, it is optimal when it can be performed with as little pain and inconvenience as possible for the patient. Optimal surgical treatment is streamlined or facilitated to the point that it is indistinguishable from nonsurgical treatment in terms of patient discomfort and cost, and is tooth-site specific when possible.

[0115] Pocket therapy is a routine treatment for periodontitis and can involve surgical or non-surgical techniques. As described above, periodontitis destroys supporting tissue and bone in the periodontal tissues, forming pockets that provide a viable ecosystem for pathogenic bacteria. Deep pockets attract more bacteria, resulting in further bone and tissue loss and ultimately tooth loss. During a periodontal pocket reduction procedure, a periodontist retracts the gum tissue to remove pathogenic bacteria, for example, via mechanical debridement, before fixing the tissue in place.

[0116] In some cases, the irregular surfaces of damaged bone are shaped to limit areas where pathogens can hide, allowing gum tissue to better reattach to healthy bone and tooth surfaces.

[0117] A practical approach to non-surgical periodontal therapy (Phase I therapy) includes the therapeutic benefits of scaling and root planing, combined with periodontal debridement for the enhancement of root planing.

[0118] The American Academy of Periodontology (AAP), a professional organization of the American Dental Association, has treatment guidelines that stipulate that periodontal health should be achieved in the least invasive and most cost-effective manner. This is often achieved through non-surgical Phase I periodontal treatment, which includes root planing and scaling (careful cleaning of the root surfaces to remove plaque and calculus (tartar) from deep periodontal pockets and to lubricate the roots and remove bacterial toxins), with adjunctive therapies such as localized medications and systemic antibiotics as needed on a case-by-case basis, depending on the severity of the disease.

[0119] Enhanced scaling, as described herein, is a process in which dentists and hygienists remove bacterial plaque (biofilm), tartar, stains, food debris, and other deposits from tooth surfaces. Enhanced root planing is a separate procedure that can be performed simultaneously with scaling, but is best performed at a separate appointment when reassessment of periodontal therapy healing is repeatedly checked at each remaining pocket site in the dentition from the initial scaling during multiple visits of Phase I periodontal therapy.

[0120] Enhanced root planing, as described herein, is a definitive treatment procedure designed to remove cementum or superficial dentin that is rough, infiltrated with calculus, or contaminated with toxins or microorganisms. Specifically, enhanced root planing, as described herein, is a process in which embedded residual calculus and diseased root cementum, along with other surface contaminants, are removed from tooth surfaces to create a smooth, hard, and biologically clean surface. This helps enable the patient's oral tissues, i.e., periodontal (gum) tissue and supporting bone, to repair and regenerate on the root surfaces of the dentition. Disclosed are embodiments for enhanced root planing using dental instruments that include refined, functionally optimized working surfaces for controlled finishing by creating a functional cutting edge or working surface appropriate for both the instrument and its intended use. Enhanced root planing may include controlled finishing techniques on the cutting edge of the instrument itself applied to the implant or root surface to enhance the processes described herein, the use of antimicrobial agents or microbial intercellular mediators, and other root conditioners with root conditioning properties beyond the therapeutic characteristics of antibiotics (e.g., citric acid, tetracycline, and tetracycline derivatives). In embodiments, the disclosed formulations and treatment methods may include the use of antibiotics, root surface chemical conditioners or root conditioners such as tetracycline or doxycycline, or chelating acids such as citric acid, or combinations thereof (see G.S. Chahal, et al., ncbi.nlm.nih.gov / pmc / articles / PMC3988639).

[0121] For example, described herein are dental instruments that include smooth and sharp cutting edges that are specifically configured for dental procedures to create root surface smoothness that is as close as possible. To help minimize bacterial growth and prevent microbial regrowth on the root, the root surface smoothness should resemble white tooth enamel, kitchen glass, or other smooth surfaces, where possible. The root surface is tested for smoothness by the clinician with a special instrument during and immediately after treatment.

[0122] In most patients with advanced periodontal disease, with periodontal pocket depths of 5-10 mm or greater, favorable reductions in disease parameters occur when root planing and scaling or reinforcement root planing are repeated for each tooth at each of four to six visits over a four to six month period. Clinical studies of the disclosed embodiments herein have shown significant improvements in periodontal health four to six months after initiation of therapy, with respect to recorded bacterial scores, bleeding on pocket probing, probing pocket depth, and probing attachment level. In some patients, additional time resulted in further improvements in clinical periodontal parameters, with pocket probing depths decreasing from 8-9 mm to 3-4 mm and clinical health restored. The majority of patients with severe periodontitis and subsequent bone loss heal by repairing gingival tissue and generating new epithelial attachments to the tooth roots, and, to a lesser extent, by long-lasting connective tissue attachment, according to periodontal studies.

[0123] Early studies, such as that published in the Journal of Periodontology in 1984 by Beaumont RH, et al., showed that despite the loss of true periodontal attachment apparatus accompanied by alveolar bone loss in the periodontal complex due to bacterial plaque periodontitis induced by ligature and soft diet in beagle dogs, there appeared to be no clear difference in resistance to disease between long junctional epithelial attachments and true connective tissue attachments. Light and fluorescence microscopic evaluation showed that neither group showed significant changes in the location of apical cells of the junctional epithelium following repair and healing during the maintenance phase after active treatment. Daily tooth brushing and prophylaxis maintained gingival health in both groups.

[0124] Many patients experience little to no discomfort when root planing and scaling are performed by an experienced periodontal clinician and do not require anesthesia for pain or discomfort. However, when pocket depths associated with clinical disease parameters persist in some teeth despite the non-surgical techniques described above to restore health, studies have shown that periodontal surgery is indicated to visually ensure that root planing is performed thoroughly to allow pocket probing depths to return to the normal range of 1-3 mm and to properly complete the work of this root planing treatment.

[0125] Periodontal debridement can be defined as the removal of all subgingival plaque and its by-products, as evidenced by clinical signs of inflammation, clinically detectable plaque-retaining elements (calculus, overhangs), and detectable calculus-embedded cementum, thereby completing the root surface during periodontal instrumentation while preserving as much root structure as possible. This procedure requires clinical judgment of tissue response for the presence of any remaining inflammation, reassessment for remaining biofilm and / or calculus, and the use of tactile and visual skills. Reassessment of healing following periodontal debridement is an important mechanism for confirming efficacy by assessing the periodontal tissues for resolution of inflammation, absence of bleeding on probing, and level of attachment and gingival recession. Long-term success requires collaborative maintenance care by both the patient and clinician. The goals of periodontal therapy are to eliminate or suppress infectious microorganisms and other pathogenic factors and to establish an environment that promotes periodontal tissue health and prevents further loss of attachment. Embodiments of a non-surgical procedure are disclosed that provide a predictable and conservative approach to treating shallow to moderate and deep pockets.

[0126] Reassessment of response to the above Phase I treatment is indicated after a suitable length of time for resolution of inflammation and bleeding on probing. If reassessment following initial nonsurgical therapy indicates that areas of the mouth have teeth with persistent inflammation and infection that have not yet resolved and / or disease progression has occurred, a clinical determination is necessary regarding the reason for the lack of response and the need for further therapy, including site-specific periodontal surgery. Problems with self-care of inflammation or residual calculus and biofilm at home by the patient may require re-instruction, re-debridement, or, in some rare cases, a different chemotherapy approach. More invasive therapy may be necessary. Surgical and further nonsurgical therapy may be site-specifically required. Each individual's immune system may be capable of healing periodontal lesions in the presence of different levels of microorganisms. Reassessment of healing following periodontal debridement is the only mechanism for confirming efficacy by evaluating the periodontal tissues for resolution of inflammation, absence of bleeding, and level of attachment with changes in probing pocket depth. The final treatment endpoint was achieved when acceptable levels of calculus, biofilm, and other root surface contaminants, and altered or diseased cementum were removed, accompanied by a favorable response by the patient's immune response.

[0127] While past and current research literature evaluates most periodontal treatments, including chemotherapeutic agents, in human and animal clinical trials, these have been very limited in study populations (mostly fewer than 100 patients or animals) and lifespans (mostly six months or less), minimizing the significance of the results for assessing success with good statistical conclusions for long-term, lifelong care. In contrast, the embodiments described in this disclosure are supported by the testing and working of thousands of periodic, active diseased tooth sites in hundreds of patients, with the reported understanding that long-term success requires continued collaborative maintenance care by both the clinician and the patient working together as co-caregivers. Thus, embodiments of chemotherapeutic and mechanical agents are described that can be employed by clinicians and patients working together as co-caregivers.

[0128] In periodontal disease, microbial pathogens trigger an inflammatory host response, which, together with direct irritation by bacterial products and by-products, causes most of the destruction to periodontal tissues. For disease to develop and progress, the host must first recognize and respond to bacterial irritants at some threshold level. In most infections, the immune system attempts to localize the site of invasion and rapidly neutralize, destroy, or remove the foreign bacterial agent. The prolonged presence of bacterial plaque and its maturation and composition as microbial colonization develops triggers a persistent and exaggerated host response, the intensity of which can vary depending on the host's susceptibility. Research is ongoing to identify susceptibility and who is "high risk," as well as to identify specific risk factors.

[0129] After 4-6 visits, periodontal probing depths are recorded multiple times, with repeated scaling and root planing over a period of 4-6 months or longer (if necessary), with this repeated approach reducing the number of active diseased pockets at each remaining active or recessed pocket, and gradually reducing the pocket probing depth noted at each initial periodontal therapy visit. Site-specific therapy is the goal; a subsequent decision on no further favorable change is usually noted after a 4-6 month period. However, site-specific treatment plans may require additional time for some treatment areas, while others are ready for long-term maintenance care, and still others require Phase II therapy or other forms of dental care. During and following the completion of Phase I, Phase II, and Phase III therapy at future visits, a full detailed reassessment should be performed using the following guide to evaluate sites for lifelong success. Clinicians should include follow-up observations for each tooth, along with any recommendations for subsequent site-specific therapy.

[0130] Both observations and treatment should be carefully recorded. Evaluation of each tooth should include, among other parameters: 1. The nature of healing of gingival tissues (edema, bleeding on probing, suppuration, fibrosis). 2. Gingival structure: (enlargement, hyperplasia, thickening of the gingival margin, fissures, craters). 3. Significant pocket depth and pocket type: (depth of 4 mm or greater, in combination with gingival, periodontal, or subbony defects). The pockets indicate clinical signs of active periodontal disease. 4. Furcation involvement (primitive furcation less than 1 mm, furcation involvement greater than 1-2 mm, extensive furcation involvement with or without gingival soft tissue closure, trifurcation or bifurcation), Classes I, II, III, IV. However, a more clinically relevant classification of furcation involvement should go beyond the horizontal component of bone loss and include subclassification of furcation involvement that measures the potential vertical depth from the top of the furcation toward the apex. The subclasses are A, B, and C: "A" indicates a probable vertical depth of 1-3 mm, "B" 4-6 mm, and "C" 7 mm or greater from the top of the furcation toward the apex. Thus, furcations are classified as IA, IB, IC, IIA, IIB, IIC, and IIIA, IIIB, IIIC. Reference: Classification of the Vertical Component of Furcation Involvement. Tamow D, et al. J. Periodontol. 1984. 5. Pockets near or beyond the mucogingival junction: (Following conventional surgical pocket resolution, determine if a functional attached gingival area is present or remains post-operatively - see #7 below). 6.Radiographic assessment: bone defects (craters, subcrestal bone on 1st, 2nd and 3rd walls). 7. Functional gingival attachment zone: Determine whether forces generated by functional movement of the alveolar mucosa, frenulum, and muscle attachments are completely dissipated by the attached gingiva. Clinically, there is no bleeding, no pain on periodontal probing, and no probing beyond the mucogingival junction. Monitor for the development of further gingival recession. 8. Zonules and muscle attachments related to the fissure or preventing surgical pocket depth resolution. 9. Vestibular depth: Determine whether it is sufficient to allow a functional gingival attachment area after pocket resolution. 10. Changes in tooth mobility patterns.

[0131] Reassessment should only be a tentative guide and should be flexible and tooth-specific, with future changes in therapy possible as dictated by changes in periodontal health. Furthermore, as therapy progresses, continued evaluation should be routine. A complete evaluation is required at each recall visit for periodontal maintenance.

[0132] Furcation involvement is a common finding in cases of severe periodontitis.

[0133] The goal of managing furcation findings, whether there is a vertical or horizontal component as explained and defined above (see paragraph 4), should preferably be furcation resolution, and creating an environment of at least sufficient furcation resolution, so that hygiene to control regrowth of the affected furcation microflora can be maintained by both the clinician and the patient, enhancing the patient's ability to maintain optimal oral hygiene. Disclosed are embodiments of combined chemotherapy / biomechanical intervention during Phases I, II, and III that may further enhance the success of lifelong retention of furcations in molars and premolars using the methods of the present invention.

[0134] Detailed reassessments using the above and subsequent guidelines should be conducted during and after future visits for Phase I therapy, Phase II (surgical) therapy, and Phase III (maintenance therapy). Traditionally, the purpose of the reassessment is to carefully examine the gingival tissue response to the initial Phase I therapy, which includes removal of calcified deposits, oral supragingival and subgingival biofilm (bacterial plaque control), oral physical therapy, temporary stabilization, occlusal adjustment with selective grinding, orthodontics, and endodontic therapy, to determine any subsequent treatments that may be indicated. As each of the clinician's observations is recorded, any indicated treatments should follow, such as periodontal bone surgery, mucogingival surgery with augmentation techniques, guided tissue regeneration, and autologous and allogeneic bone grafts. The reassessments listed above in the preceding paragraphs are merely tentative guides and should be flexible and tooth-specific, with future therapy subject to change as dictated by changes in periodontal health. Furthermore, as therapy progresses, continued evaluation should be routine. A complete periodontal evaluation is required at each Phase III recall visit for periodontal maintenance.

[0135] As described above, periodontal therapy involves multiple treatments, including tooth extraction, occlusal modification, implant therapy, and pocket therapy. Typically, the goals of periodontal therapy are to eliminate pain, halt and reduce pocket formation, reduce abnormal tooth mobility, halt soft tissue and bone destruction, and restore lost tissue, among others. Desired tissue responses, particularly for localized and systemic treatments, include: restoration of epithelial surface continuity, reattachment of connective tissue between alveolar bone 21 and cementum 7, reattachment of cementum 7 to periodontal fibers, and restoration of the balance between alveolar bone 21 formation and resorption. Desired clinical outcomes include resolution of pus formation, gingival bleeding, and inflammation, resolution of periodontal pockets and infection, restoration of destroyed periodontal tissue, reduction of abnormal tooth mobility, halt of bone loss, and restoration of healthy gingival contours.

[0136] Local therapies also include biofilm removal and treatments to reduce the symptoms of biofilm buildup. Other local therapy treatments include elimination of traumatized tissue to increase the likelihood of bone regeneration and attachment. Local therapies also include creating a favorable occlusal relationship for the periodontal tissues, particularly reducing tooth mobility and increasing the margin of safe plaque biofilm in the periodontal tissues.

[0137] Systemic therapy is an adjunct to local therapy that targets specific treatment challenges, such as controlling systemic complications from acute infection, chemotherapy to prevent the harmful effects of post-treatment bacteremia, supportive nutritional therapy, and controlling systemic diseases that may complicate periodontal treatment or require special attention. Traditional systemic therapy includes systemic antibiotics to eliminate bacteria that invade the gingival tissue and may re-invade and repopulate the pockets. Other systemic treatments, including NSAIDs such as ibuprofen and flurbiprofen, have been reported to slow the development of gingivitis and alveolar bone loss.

[0138] In one or more embodiments, the method includes providing a peroxide gel, e.g., a gel solution comprising 10% urea peroxide, for administration to a treatment area of ​​a subject in conjunction with a dental care treatment; and administering to a subject a peroxide gel containing 10% urea peroxide, e.g., a gel solution comprising 10% urea peroxide, e.g., a 10% urea peroxide gel containing tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, or a combination of ... A dental treatment method is described that includes providing a viscous antimicrobial agent containing a clinically effective amount of at least one, or in other embodiments at least two, or in still other embodiments at least three, of a topical antibacterial agent, a topical antiviral agent, a topical antifungal agent, a topical antiseptic agent, a topical antimicrobial interaction agent, or a topical antibiotic, including a combination of cephalexin, ofloxacin, metronidazole, and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin, to a treatment area of ​​a subject during dental treatment. In one embodiment, a peroxide gel solution chemically debrides and anesthetizes the treatment area.In embodiments, the viscous antimicrobial agent is selected from the group consisting of tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, In another embodiment, the topical antibacterial agent or topical antibiotic comprises at least one, or in another embodiment, at least two, or in yet another embodiment, at least three of the following: a topical antibacterial agent, a topical antiviral agent, a topical antifungal agent, a topical antiseptic, a topical antimicrobial agent, or a topical antibiotic, including cephalexin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and derivatives thereof; and a combination of minocycline, metronidazole, and ciprofloxacin.

[0139] In embodiments, administering a gel solution comprising peroxide to the subject's periodontal pocket in conjunction with mechanical debridement treatment, wherein the peroxide gel solution chemically debrides and anesthetizes the treated area of ​​the periodontal pocket; and administering to the subject a therapeutically effective amount of any of the following: tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, ... and a combination of minocycline, metronidazole, and ciprofloxacin.

[0140] A wide range of peroxide gels can be used. For example, gels can contain peroxide compounds, hydrogen peroxide, urea peroxide, debridement oxygenation materials, or any other agent. The peroxide agent is provided in a gel or viscous state. Exemplary gel solutions include hydrogen peroxide gels, e.g., gels with 1.7% (w / s) hydrogen peroxide (e.g., Periogel®), urea peroxide (hydrogen peroxide-urea) gels that decompose into hydrogen peroxide and urea, e.g., Glyoxide®, which contains 10% urea peroxide and produces approximately 3.5 percent hydrogen peroxide upon decomposition. Peroxide gel concentrations can range from a minimum of 1.5% to a maximum of 44%.

[0141] In an embodiment, the method comprises administering a gel solution comprising at least 10% urea peroxide to the subject's periodontal pocket in conjunction with mechanical debridement treatment, wherein the peroxide gel solution chemically debrides and anesthetizes the treated area of ​​the periodontal pocket; and administering one of the following: tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, or the like. A method for treating periodontal disease is disclosed, comprising administering to a subject's periodontal pocket during mechanical debridement treatment an antimicrobial agent consisting essentially of at least one of a topical antibacterial agent, a topical antiviral agent, a topical antifungal agent, a topical antiseptic agent, a topical antimicrobial interaction agent, or a topical antibiotic, including cephalexin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin. The various antimicrobial or antibiotic gels or pastes can be administered together or separately.

[0142] In embodiments, the present specification describes the use of sharpening tools to provide dental instruments with optimized functional working surfaces, e.g., optimized cutting edges or cutting edges. These optimized dental instruments and working surfaces, along with the microbiological rates of other organisms such as viruses, fungi, amoebas, and other parasites, can affect the controlled surface roughness to control or limit bacterial growth rates or selectively limit bacterial growth and the potential for selective bacterial flora to attach to dental roots and implants. This can enhance the effectiveness of antimicrobials and antibiotics during Phase I, Phase II, and Phase III treatment, as well as surgical regeneration and surgical epithelial and connective tissue repair and root reattachment procedures. Thus, when sharpening tools are used to refine dental instruments and optimize their working surfaces, either indirectly or directly, enhanced root planing and scaling using such instruments during Phase I, Phase II, and Phase III can be antimicrobial and help prevent the regrowth of certain bacterial species in preference to others.

[0143] In embodiments, antibiotics may be administered directly into the periodontal pocket before and / or during mechanical debridement, including tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, methadone ... The composition may be a powder, such as a powder formulation of a combination of minocycline, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin, which acquires a viscous paste-like consistency. In embodiments, a pharmaceutical agent including a solution and an antimicrobial agent may be administered in conjunction with a treatment. In embodiments, a treatment may include non-surgical treatment of severe periodontitis, such as in the areas of furcations of molars and some premolars. For example, diseased premolars may have deep vertical pockets in the molars and some premolars where the pockets follow a tortuous path into the furcation with horizontal and vertical paths. Trays and other such delivery mechanisms cannot reach these pockets and cannot conform and fit under the clinical tooth enamel crown.

[0144] In embodiments, during non-surgical mechanical debridement periodontal disease treatment, the treatment can be administered to a subject with a pocket depth of 5 or more millimeters. For example, the treatment can be applied to a periodontal pocket depth of at least 7 millimeters or even at least 10 millimeters. It is understood that in assessing measurements, the root surface length and individual anatomical structures of the root and surface topography found on molars, premolars, canines, and incisors may vary. Therefore, the degree of periodontal attachment loss, whether hard or soft tissue, may be a determining factor in periodontal probing of pocket depth. Teeth such as molars and some premolars may also have furcation disease with pocket progression continuing within or between their multiple roots, and these furcations may be further defined by the loss of periodontal bone attachment and soft tissue attachment to their root surfaces using periodontal probing.

[0145] In embodiments, an effective amount of 10% urea peroxide solution is applied as an anesthetic, eliminating the need for injectable anesthesia, such as lidocaine (xylocaine). This allows the treating periodontist, dental clinician, hygienist, or general dentist to apply treatment in pocket depths greater than 3 mm and at least 5 mm without the need for other anesthesia, including up to at least 7-10 mm, as described above. Traditionally, periodontist dentists have had to administer topical or injectable known anesthesia, such as lidocaine or novocaine, or stronger anesthesia, for such invasive mechanical debridement. Indeed, many patients are hesitant to receive dental care due to anxiety, such as anxiety about dental treatment, local anesthesia, or past dental experiences. Furthermore, local anesthesia can cause pain, stinging, and burning upon injection, which can adversely affect patient anxiety. Dental hygienists and dentists have a unique responsibility and opportunity to provide pain relief. The use of 10% urea peroxide or topical anesthesia completely avoids the use of local injectable anesthesia during non-surgical Phase I therapy. Refined dental instruments with optimized working surfaces, such as sharp, smooth cutting edges on dental curettes and scalers, and good clinical instrumentation and clinical skills, help ensure a level of patient comfort and encourage cooperative, non-anxious patients to return for continued dental care, while avoiding the use of post-treatment analgesics. The vast majority of patients do not require local dental anesthetic injections or intensive root planing procedures during scaling and root planing, except during Phase II surgical care. In embodiments, the use of the disclosed pharmaceutical formulations can completely avoid the use and need for Schedule I, II, III, IV, and V analgesics. Thus, the disclosed pharmaceutical formulations and their use in dental therapy are advantageous in that they are free of any Schedule I, II, III, IV, and V analgesics.

[0146] Root desensitization products should also be used primarily where root instrumentation is a concern at specific tooth sites where discomfort may result, thereby avoiding the use of local anesthetics for pain management.

[0147] It is anticipated that embodiments of the techniques and methods described herein will accommodate changes in the standard of care.

[0148] As can be seen, properly sharpening the working edges of dental tools, such as curettes and other scalers, further reduces the need for strong anesthesia. When administered in conjunction with properly sharpened dental tools with functionally optimized working surfaces, treatment can smooth the root surface from 1-5 microns to 1 micron. Root preparation to this degree of smoothness renders the root unviable for bacteria and pathogens because bacteria are unable to attach to it. Thus, repeated application of the gel's chemical debridement properties has made it possible to non-surgically treat many pocket sites measuring 5 mm and even greater than 10 mm without surgery. Smoothing the root down to nearly 1 micron results in the smoothest possible surface finish. As can be seen, removing various bacterial and non-bacterial materials supragingivally and from exposed pockets / sulci helps reduce future bacterial recolonization of smooth root surfaces. The unique chemical approach described in the embodiments herein achieves chemical curettage and root preparation that improves the removal of bacteria and non-bacterial materials. Antibacterial and antimicrobial approaches, in conjunction with chemical curettage and the use of optimally sharpened tools, provide the most successful treatment and future preventative management of periodontal and dental caries / caries prevention. In various embodiments, periodontal treatments are described that include a series of medications that are mechanically administered intraorally by professionals and patients to provide an effective, practical, safe, and affordable means of controlling periodontal supragingival and subgingival colonization and caries-causing bacteria for various types of disease.

[0149] The embodiments described herein can be employed to establish professional guidelines for optimal periodontal care, which require that root surfaces be scaled and root planed as smoothly and biologically clean as possible to minimize bacterial regrowth on the root surfaces, which leads to the maturation of bacterial plaque that causes dental caries and periodontal disease, and thus may help prevent higher indices of periodontal and dental caries disease in the population.

[0150] Many research papers published in the dental literature have determined the importance of using properly sharpened and shaped curettes during biomechanical root preparation in periodontal therapy. For example, a recent publication by Rossi and Smukler in The Journal of Periodontology noted the importance of using curettes sharpened and shaped with finer grit stones and abrasives because they create smoother, finer root surfaces than those sharpened with coarser grit stones or abrasives. The highest grit numbers (highest number of grains per square inch) created the smoothest and sharpest cutting edges, and these abrasives were aluminum oxide and Arkansas abrasives (before the optimized sharpening and shaping tools described herein were available). They concluded that the smoothness of the planed root of a tooth is related to the type of stone or abrasive used during the sharpening or shaping process. As will be appreciated, the present disclosure includes an optimized sharpening technique that sharpens and shapes curettes 5 to 6 times finer than the aluminum oxide and Arkansas abrasives available in that study. Quirynen and Bollen reported on the effects of surface roughness and surface free energy on subgingival plaque formation in humans. Journal of Clinical Periodontology (January 1995). These authors reported on the iatrogenic effects of biomechanical preparation of tooth roots during periodontal therapy, resulting from instruments obtained in brand new condition from the dental manufacturer, and their influence on promoting bacterial plaque formation due to severe metal deformation and wire edges extending along the cutting edge itself. Rough surfaces are known to promote plaque maturation, and high-energy surfaces attract more plaque, bind plaque more tightly, and select for specific bacteria.The current world consensus document on appropriate periodontitis treatment (The Annals of Periodontology: Proceedings of the World Workshops in Periodontics, November 1996) supports and cites the work and ideas of this extensive review article by Quirynen and Bollen on the importance of creating smooth root surfaces as the goal of appropriate biomechanical periodontal therapy.

[0151] Although both variables interact with each other, the effect of surface roughness overwhelms the effect of surface free energy. In the subgingival environment, where it is easier for microorganisms to survive, surface features become less important. However, the effects of surface roughness and surface free energy on supragingival plaque justify the need for smooth surfaces with low surface free energy to minimize plaque formation, thereby reducing the incidence of dental caries and periodontitis in the global population. Thus, in embodiments, tool shaping and sharpening can be performed in conjunction with each treatment using optimized sharpening tool technology described in U.S. Patent Nos. 6,074,293, 6,361,408, 6,949,018, U.S. Patent Application No. 15 / 241,252, and International Patent Application No. PCT / US2015 / 041998, the entire contents of which are incorporated herein by reference (e.g., Honing Channel® Sharpening System). The design and engineering aspects of this technology serve to meet clinical treatment needs defined by current dental research, ultimately benefiting patients.

[0152] Thus, in at least one of various embodiments, the dental treatment includes sharpening the dental instrument working surface with a sharpening tool configured to create a cutting edge that optimizes the working surface of the blade, so that the dental treatment is performed with the optimized blade. For example, during mechanical debridement, such as enhanced root planing, the care professional uses a sharpening tool with an abrasive to sharpen the dental instrument to highly smooth the root of the tooth and minimize biofilm regrowth on the root surface, in conjunction with the antimicrobial and antibiotic agents described herein, such as topically applied urea peroxide gel and topical antimicrobials such as tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, thiamin ... Topical antibacterial, antiviral, antifungal, antiseptic, antimicrobial, or antibiotic agents may be used during treatment, including: cefacillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and minocycline, a combination of metronidazole and ciprofloxacin. In embodiments, the patient (or patient caregiver) may also periodically use antimicrobial agents, such as 10% urea peroxide and even topical fluoride, on the roots of the teeth to minimize the risk of dental caries. For example, patients or their caregivers may be instructed to floss with a gel solution containing at least 10% urea peroxide and to use topical fluoride (e.g., Prevident®) during periods of active disease and even later during long-term maintenance care.

[0153] In at least one of various embodiments, in conjunction with each treatment, the dental tool is sharpened to a fine cutting edge, thereby transferring the smoothness and sharpness of the tool's functional surface onto the root surface. The optimized dental tool can then be used in conjunction with the pharmaceutical methods described herein to achieve greater success and minimize periodontal and caries disease indices.

[0154] In at least one of various embodiments, the mechanical treatment involves smoothing the root to a root surface of approximately 1-5 microns using enhanced root planing. The surface finish is as smooth as possible, removing various bacterial and non-bacterial materials, which helps treat disease in the supragingival margin and exposed pockets / sulci, and also helps prevent disease by reducing future bacterial recolonization of the root surface. As described herein, in embodiments, dental tools can be sharpened to obtain an optimized cutting edge of 1-5 microns, which can also produce a root surface finish of 1-5 microns. The sharpened tools described herein can also create an optimized cutting edge without wire edges.

[0155] Since 1995, advances in research, development, and optimized sharpening tool technology, as described in U.S. Patent Nos. 6,074,293, 6,361,408, and 6,949,018, U.S. Patent Application No. 15 / 241,252, and International Patent Application No. PCT / US2015 / 041998, have resulted in channels designed to properly reshape or re-sharpen either European or American curettes and sickle scalers. For example, the Honing Channel® Sharpening System for Curettes and Sickle Scalers includes high-strength, custom-designed aluminum oxide sharpening and shaping stones. Because sizes vary among instrument manufacturers, these ceramic stones have tolerances built into the channels to accommodate most curettes and scalers used by the majority of dental professionals worldwide. For example, based on the World Workshop on Periodontal Therapy, White Honing Channel® wheels were created with the highest grit size (highest number of particles per square inch) and highest density; one of its primary purposes is to provide the sharpest and finest cutting edge possible, which is necessary for successful quality periodontal therapy. In an embodiment, the White Honing Channel® wheel comprises a 0.472" x 0.984" x 3.93" (1.19 cm x 2.49 cm x 9.98 cm) stone that weighs 3.5 oz (99.2 g).

[0156] In another embodiment, the Chocolate Honing Channel® stone includes a 0.495" x 1.03" x 3.93" (1.25 cm x 2.61 cm x 9.98 cm) stone that weighs 3.3 oz (93.5 g). In another embodiment, the sharpening tool can be tested for sharpness using the included 0.2 oz (5.66 g) 3.93" (9.98 cm) sharpening stick.

[0157] In various embodiments, the optimized sharpening tool technology described herein improves the quality and delivery of dental treatment and health care by clinicians, ultimately benefiting patients, by properly preparing dental instruments for clinical use based on currently accepted professional standards and the high professional standards of care proposed herein. An optimized sharpening tool consistently provides the smoothest, sharpest cutting edge on any metal alloy, ceramic, or plastic of any manufactured instrument, by anyone using it. As described herein, dental research studies have shown that the smoothness of root surfaces in periodontal treatment is directly determined by the smoothness and finish of the dental instrument's cutting edge, and that cutting edges finished with those stones having the highest grit size and finest abrasion level (highest grit) produced the smoothest, finest cutting edges transferred to root surfaces during scaling and root planing treatment. Despite this, as of the filing of this application, new dental curettes and scalers are not properly finished. Because they come from the manufacturer, they first require proper finishing to remove any wire edges found on the cutting edges of these new instruments before they can be used in treatment. Additionally, just 15–30 strokes on the root of a tooth can visibly dull and damage the cutting edge. Therefore, the cutting edges of instruments constantly require reshaping and resharpening during patient visits. Optimized tool technology, such as the Honing Channel® sharpening and shaping channel, allows for quick reshaping and resharpening of just the cutting edges of curettes and sickle scalers with just one to three strokes within the channel, saving clinic time. Optimized disinfectant technology simplifies the entire sharpening procedure, allowing licensed medical / dental clinicians to sharpen tableside while providing patient care, and now allows unlicensed technicians in a laboratory or disinfectant / technician area to sharpen all types of curettes and scalers and prepare them for use in treatment with less than one hour of training.Regardless of who on the medical / dental team uses the product, it produces the same precise, consistently sharp, highly refined cutting edge that follows its original geometric design for consistent quality care, unlike the previous traditional "flat stone" sharpening techniques used to this day.

[0158] Previously, the manufacture of scalers and curettes has been performed by hand using flat or round abrasives, which requires the utmost skill of the technician or clinician to find the precise angle between the instrument and the shaping and sharpening device. Significant difficulties are encountered in finding this precise angle on the dental-medical instrument and maintaining it along the entire length of the cutting edge during the sharpening and shaping process. Furthermore, one of the problems with finishing these complex surfaces, especially curved surfaces (such as those found on the cutting edges of curettes and scalers), is the need to drag the article over the abrasive surface while continually changing the angle to accommodate its geometry. Finishing complex surfaces typically requires skilled hands, experienced craftsmen, or complex robotic manufacturing machinery. Due to the tight control required, even experts find it difficult to follow many complex surface shapes.

[0159] In the manufacturing industry, determining the conditions for a finishing process to obtain a specified surface topography is also not without problems, as it involves many interacting factors. Under ideal circumstances, factors to be considered include the machine operating settings (e.g., abrasive tool geometry, working speed, tool feed rate, and type of cutting fluid used).

[0160] Even under ideal conditions, calculating the theoretical roughness that occurs in a machining operation has been a very simple process, i.e., a single-point tool cut. The fact that it is not possible to fully specify the surface features and the surface scale and topography remains a serious problem for production / design engineers.

[0161] One aspect of embodiments of sharpening tools relates to the finishing of surfaces on tools and instruments. For example, dental, veterinary, and medical instruments can have sophisticated shapes that can only be obtained through precise and complex finishing procedures. Thus, in at least one of various embodiments, a sharpening tool is described that precisely provides a precisely shaped cutting edge on dental tools, such as dental curettes, that is suitable for proper biomechanical root surface preparation in periodontal therapy. The device not only provides the correct shape to the cutting edge of the curette, but does so with high precision every time. By using this optimized sharpening device, the dentist or technician performing the finishing does not need to be so careful as to drag the instrument over the grinding surface. The optimized sharpening device has one or more grinding surfaces specifically shaped to guide and shape the instrument surface. These grinding surfaces of the channels in the optimized sharpening tool create a precise shape for the cutting edge of the curette. The shape of the channel provides the smoothness and precision of the curette's original design, which is transferred onto the root surface. Cutting edge smoothness was determined to be between 1 and 5 microns, producing a finer root surface finish than had previously been achievable.

[0162] Research, development, and technological advances in the ceramic field have resulted in custom-designed aluminum oxide sharpening and shaping stones. The concept of sharpening and shaping channels now allows most licensed and unlicensed dental practitioners to learn to sharpen curettes with less than an hour of training, thanks to this application of optimized sharpening tools. Hygienists and dentists can now quickly and accurately sharpen their own scalers and curettes, or delegate this responsibility to a technician or assistant to properly sharpen and finish the instruments in preparation for use, saving professionals significant time and money. Research has shown that most graduating dentists and hygienists are unable to consistently and adequately sharpen their necessary dental instruments due to inadequate academic professional training during their professional careers, and this problem continues throughout their professional careers. A key aspect of professional practice is proper instrument preparation before use, which, to date, is seriously overlooked for each patient during dental treatment and is clearly a healthcare problem worldwide. This product can help re-motivate professionals to perform sharpening for each patient and fulfill this necessary responsibility in service to their patients. These engineered sharpening channel stones have not previously been available with precise channel designs. Applications of these patents extend to the medical and veterinary fields and other manufacturing lines.

[0163] The optimized sharpening tools in the embodiments described herein consistently maintain instruments in line with their original geometric design, extending instrument life by minimizing wear and abrasion, unlike other grinding stones (Arkansas grinding stones) used in dentistry, and restoring tooth roots to near their original level of surface smoothness. Furthermore, no oil lubrication is required, and instruments can be tableside during each patient treatment visit when autoclaved and precisely sharpened tableside for each patient in the treatment room. Dental teams can now consistently sharpen and create and restore the same cutting edge regardless of who uses it, unlike other techniques (e.g., flat stones that try to be positioned at a precise angle or shape).

[0164] Thus, in at least one embodiment, a method comprises providing a finishing tool for sharpening a dental instrument. Exemplary sharpening tools are described below and in U.S. Patent Nos. 6,074,293, 6,361,408, 6,949,018, U.S. Patent Application No. 15 / 241,252, and International Patent Application PCT / US2015 / 041998, each of which is incorporated herein by reference in its entirety.

[0165] For example, in at least one of various embodiments, a method can include using a finishing tool to surface finish complex and simple surface geometries by abrading selected areas of the surface and leaving continuous areas unfinished. The device can be simple in construction and require little training to operate. The device can include, in a cross-sectional profile, an abrasive surface that is a negative image of the surface area to be abraded or finished, and a relief surface that corresponds to that area or the area that will remain unfinished.

[0166] In an embodiment, an apparatus for finishing an area on a surface of a dental instrument, wherein the surface comprises a plurality of adjacent, contiguous areas, includes: a means for supporting a hard abrasive surface; (i) a cross-sectional profile that is a negative image of the profile of the area to be finished; and (ii) a non-flexible abrasive surface supported on the means for supporting the abrasive surface, the abrasive surface having a relief corresponding to the area or areas that are to remain unfinished.

[0167] The abrasive surface may further include a relief connecting and underlying the pair of sharpening regions, the relief corresponding to the area or areas that are to be left unfinished. The finishing region may be a straight surface or a curved surface. The device may accurately provide a precisely shaped cutting edge to the bladed instrument.

[0168] The device not only provides the precise shape for the cutting edge of the bladed instrument with high precision every time. In certain embodiments, the finishing device is configured to facilitate drawing the instrument, e.g., a dental curette, over the grinding surface of the device. The instrument itself is typically held at a specific angle relative to the grinding surface, but even this is not essential. The device can have one or more grinding surfaces specifically shaped to guide and finish the instrument surface. These grinding surfaces create the precise shape for the cutting edge of the curette. The shape provides the smoothness and precision of its original design. Thus, the grinding surface element of the device not only creates the precise shape of the desired cutting edge of the curette, but also a cutting edge with the appropriate edge smoothness and precision required in current research-based dentistry. The tool can be configured to sharpen multiple different bladed instruments or working surfaces by configuring a single finishing device and finishing process with surface finishing for surface topography or shape, cross-section, shaping, sharpening, and surface roughness control for multiple bladed instruments (e.g., one area for dental curettes, one area for scalers, one area for surgical scissors, etc.).

[0169] In embodiments, sharpening and shaping devices for dental and surgical instruments may include a hard block, an abrasive material designed to grind, cut, or otherwise shape the metal surface of the instrument, the block generally having a flat upper surface with at least one sharpening and shaping groove located therein, the at least one groove receiving the distal end of the instrument for the purpose of sharpening and shaping the distal tip as the instrument is drawn therethrough, the at least one groove having an effective cutting surface for shaping the distal tip and a relief surface for guiding the distal tip in a non-cutting manner.

[0170] In embodiments, a finishing device for the surface of an appliance may include a block containing an abrasive material designed to polish, cut, or otherwise finish the surface of a dental appliance, said block having a unitary block structure including a finishing cavity disposed therein, said cavity including at least a portion of a negative image surface of the portion of the appliance to be finished, said cavity further including at least one groove formed therein for receiving the distal end of the tool or appliance for finishing the distal end as the tool moves relative to said at least one groove, said at least one groove having an effective cutting surface for finishing the distal end.

[0171] In embodiments, an apparatus for finishing an area on a surface of an implement may include a support with a hard, abrasive surface; and one or more channels supported on the support, each of the channels having a cross-sectional profile including at least one finishing region for finishing the operational area of ​​the article, optimizing the clearance portion of the article, where the finishing region includes a contact region and a non-contact region, where the angle of each finishing region in the cross-sectional profile is substantially the same as the optimal clearance angle of the article, and where the apparatus is configured to position the operational area of ​​the article along the angle of the finishing region during sharpening. In certain embodiments, the one or more channels may each include a pair of finishing regions. In certain embodiments, the clearance angle β of the article is calculated as β = 90° - γ - α, where α is the rake angle and γ is the cutting edge angle. Exemplary sharpening tools are described in U.S. Patent Application No. 15 / 241,252 and International Patent Application No. PCT / US2015 / 041998, the entire contents of which are incorporated herein by reference.

[0172] Research studies by Leknes, Lie, Wikesjo, Boe, and Selvig in the Journal of Periodontology in 1994 and 1996 showed that subgingival root instrumentation characteristics, using different abrasives and creating different levels of surface root roughness, altered bacterial recolonization. These studies demonstrate that altering the roughness of subgingival instrumentation can significantly affect subgingival microbial colonization. These studies also found that subgingival root instrumentation characteristics, by altering the roughness of tooth instrumentation, significantly affected the gingival inflammatory response, most likely by affecting subgingival plaque. This contributes evidence as to why the embodiments described herein work by using high levels of mechanical root smoothing and chemical techniques, where mechanical treatments (flossing, brushing, stimulation) are performed by clinicians in the office in conjunction with chemical treatments (e.g., peroxide gel, peroxide gel in conjunction with fluoride paste) performed by patients at home.

[0173] The unique chemical approach described herein, alone or in conjunction with optimized dental tools for mechanical treatment, helps achieve the same beneficial therapeutic effects associated with chemical curettage and root preparation, thereby improving the removal of the same bacterial and non-bacterial substances as antimicrobial approaches, resulting in the most successful treatment and future preventative management of periodontal and dental caries / caries prevention. The approach includes and recommends periodontal treatments that include a range of professional- and patient-administered medications that are mechanically applied intraorally to provide an effective, practical, safe, and affordable means of controlling periodontal supragingival and subgingival colonization and caries-causing bacteria for various types of disease.

[0174] In embodiments, the method includes administering a first dose of antimicrobial therapy before administering a first application of the solution. In embodiments, the method includes administering a first application of the solution before administering the antimicrobial therapy. In another embodiment, the solution and the antimicrobial therapy can be administered simultaneously. For example, the therapy can be administered via a single delivery mechanism, e.g., a pharmaceutical product that includes both the solution and the antimicrobial therapy in a stable, viscous gel solution that can be applied to the treatment area.

[0175] In embodiments, the method comprises repeating the treatment multiple times during the active phase of the disease. For example, as described above, the non-surgical phase treatment is followed up by assessment, particularly checking pocket depth and gingival inflammation, and rechecking for biofilm, tartar, and caries. Thus, in embodiments, the treatment comprises applying or delivering a solution containing peroxide to the subject's periodontal pockets; and administering to the subject a solution containing tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin. The method may include administering a follow-up treatment to the subject's periodontal pockets during follow-up, comprising applying or delivering to the periodontal pockets a clinically effective amount of a topical antimicrobial, topical antiviral, topical antifungal, topical antiseptic, topical antimicrobial interaction agent, or topical antibiotic, including norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin. Treatment may be continued at some or all of each follow-up visit during the active phase of disease. In embodiments, treatment may also be continued one or more times through a maintenance phase of treatment.

[0176] In embodiments, the method includes instructing the subject to floss with a gel solution containing 10% urea peroxide at least once daily during the active phase of periodontal disease. In embodiments, the method may also include instructing the subject to brush their gums with a gel solution containing 10% urea peroxide at least once daily during the active phase of periodontal disease. In embodiments, the method may include instructing the subject to continue regular flossing with a gel solution containing 10% urea peroxide at least once daily during the maintenance phase of periodontal disease. For example, the subject may be instructed to floss daily and / or as part of the subject's regular (e.g., daily) dental care routine. As described herein, the maintenance phase may continue throughout the subject's lifetime. Maintenance may include instructions to include site-specific application of peroxide gel, or other antimicrobial agents, fluoride, or other medicinal agents, when site-specific analysis indicates locations where periodontal disease is known to be occurring, to support continued maintenance care (e.g., patient home care).

[0177] In embodiments, in conjunction with a dental care treatment, providing a solution comprising a peroxide gel solution for administration to a treatment area of ​​a subject, wherein the peroxide gel solution chemically debridements and anesthetizes the treatment area; and administering to a subject a solution comprising tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gefitinib, cefotaxime ... Dental treatment methods are described that include providing a viscous antimicrobial agent comprising a clinically effective amount of a topical antibacterial agent, a topical antiviral agent, a topical antifungal agent, a topical antiseptic agent, a topical antimicrobial interaction agent, or a topical antibiotic, including mifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin, to a periodontal pocket or wound site of a subject during dental care treatment. Dental care treatments may include, for example, preparing tooth roots for bone grafting, treating or preventing peri-implant mucositis and peri-implantitis (e.g., due to titanium implants), treating dental surgical tissues with autologous or allografts and other materials in surgical procedures to treat the subject's tooth root (e.g., root planing or root preparation, or root canal treatment).Tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, amoxicillin and clavulanic acid combinations, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin The use of cephalexin, norfloxacin, ofloxacin, metronidazole and amoxicillin combinations, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and minocycline, metronidazole and ciprofloxacin combinations may also be used with surgical membranes placed with hard and soft tissue grafts associated with edentulous ridges and dental implants or natural tooth roots. These chemotherapeutic agents not only act as root conditioners but also assist in the surgical debridement and wound preparation of adjacent vital soft and hard tissues, whether supporting natural teeth, dental implants, edentulous ridges, various surgical membranes, or tooth extraction sites, minimizing postoperative pain, swelling, and other sequelae such as infection.

[0178] Practitioners who have not experienced implant failure or complications are likely to have not performed them adequately or to have their patients seek care from another physician for treatment of the problems they are experiencing. While dental implants have been reported to achieve long-term success, they are not immune to complications related to improper treatment planning, surgical and prosthetic execution, material failure, and maintenance. These complications, which are biological in nature, include peri-implant mucositis and peri-implantitis, which are inflammatory conditions in the soft and hard tissues around a dental implant.

[0179] In at least one of various embodiments, the method may further include: sharpening or finishing the dental instrument working surface with a finishing tool; and performing an optimized surface finish for the dental implant with the sharpening or finishing dental instrument. The finishing tool is configured to create an optimized working surface of a cutting edge or functional edge, whereby the implant surface finishing treatment is performed on the optimized working surface. The finishing tool may be configured to create an optimized working surface for the instrument, including, for example, no wire edges, no deformations, and / or a working surface that is finished to the tolerances of the implant.

[0180] In embodiments, tools are provided with optimized working surfaces that can create a controlled finished surface for an implant in vivo. For example, a finishing tool can be configured to retap or reshape the body of an implant. The tool can include a reverse thread to finish, resurface, or recut the threads of an implant, depending on the patient's needs, for example. For example, in certain embodiments, a thread sharpening or shaping device can include a block or housing, each of which can include one or more grooves with abrasive regions, such as those described in International Patent Application PCT / US2015 / 041998 and U.S. Patent Application No. 15 / 241,252, each of which is incorporated by reference in its entirety. The grooves form a channel when the housings are closed together. To sharpen or shape the threads, the housings can be positioned or closed over the threads, thereby positioning within the channel formed by the grooves in each of the housings. In embodiments, the grooves can have the same thread pattern corresponding to the threads on the implant screw. Thus, when the screw is positioned within the groove channel, rotating the screw along the threads imparts a specific shape to the screw threads with high precision. In embodiments, the channel can be configured to impart different shapes or controlled surfaces to the implant, for example, to remove or reshape threads that collect contaminants. Finishing and shaping surfaces can include surfaces for taps, tap dies, plasma sprays, burnishing, and thread cleaning. In embodiments, the thread sharpening or shaping tool can be configured to be attached to an implant drill or implant removal wrench for in vivo use.

[0181] In various embodiments, instruments are finished to a controlled surface finish that is optimal for the instrument's use. For example, instruments for finishing bone for bone grafting may be finished to a roughness (e.g., on the order of hundreds of microns) that promotes successful implantation due to osteoblast activity or bone cells responding to increased bone roughness. In another example, finishing tools may be configured to create a smoother finish, e.g., 1-99 microns, to create an implant surface that should be biologically clean. The finish may allow for placement of a sprayed or applied root conditioner.

[0182] Controlled finishing is also expected to enhance emerging new therapies, such as wound healing and bone regeneration techniques using growth factor-enhanced matrix (GEM 21S®), an implant material consisting of a concentrated solution of pure recombinant human platelet-derived growth factor (rhPDGF-BB), a synthetic form of the body's important natural wound healing stimulator, PDGF-BB, and beta-tricalcium phosphate (β-TCP), an osteoconductive (bone scaffold) matrix.

[0183] One or more embodiments, including those with applied chemotherapeutic agents as described herein, have also been shown to be effective on biofilm-contaminated titanium surfaces in the treatment of peri-implant mucositis, peri-implantitis, and in the prevention and early detection of these conditions. Surface decontamination of the implant surface allows for successful healing by repair or regeneration and preservation of the implant's support structure. Given the common etiology of periodontitis and peri-implantitis, the approaches to the treatment of periodontitis and peri-implantitis are similar, and in more advanced lesions of peri-implantitis, the use of tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, and combinations of amoxicillin and clavulanic acid, as described herein, is recommended. The use of chemotherapeutic agents such as clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin, along with other surgical excision and regeneration techniques, may aid in surface decontamination of the implant surface.

[0184] The embodiments described herein have been determined to be effective in long-term clinical practice by preventing peri-implantitis, particularly peri-implant gingivitis, with the patient acting as co-caretaker, for example, with the use of 10% urea peroxide and a site-specific oral hygiene delivery applicator device as indicated, and with supportive periodontal therapy at determined maintenance appointments in the clinic. Topical tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, mofetil, thiazolinone ... Combinations of xyloxacin, norfloxacin, ofloxacin, metronidazole, and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and minocycline, metronidazole, or ciprofloxacin are used in the pocket site around the implant during treatment when bleeding on probing to a depth of at least 5 mm is indicated. Deeper pocket depths, particularly those associated with implants with radiological evidence of new, progressive bone loss, are addressed at follow-up appointments and reevaluations to determine the need for further intervention. Patients may be instructed to implement the treatment protocol at home and act as co-therapists. Alternatively, in some embodiments, a topical antibacterial, antiviral, antifungal, antiseptic, or antimicrobial agent or antibiotic is used in pocket sites around implants during treatment that exhibit bleeding upon probing to a depth of at least 5 mm. Deeper pocket depths, particularly those associated with implants with radiological evidence of new, progressive bone loss, are addressed at follow-up appointments and reevaluations to determine the need for further intervention.

[0185] Prevention and early detection are critical for the successful management of inflammatory diseases associated with biofilm-contaminated implant surfaces, such as peri-implant gingivitis and peri-implantitis. Similarly, in the medical field, various implant designs and materials are used to minimize bacterial colonization. Depending on the surgical requirements, orthopedic implants may contain a single material, such as fracture fixation stabilization and spinal hardware, or multiple materials, such as plastic or ceramic and metal combinations used in knee and hip implants and oral implants with cement, and / or bone grafts to enhance implant fit. In many implant procedures, plastic, ceramic, and metal combinations are implanted with bone allograft to provide complex proteins and minerals and enhance implant success and integration (osseointegration). As will be appreciated, not all implants are designed to be osseointegrated in mammalian species.

[0186] Bacterial colonization and biofilm formation on implant surfaces are among the most devastating outcomes of any medical or dental implant intervention, both in terms of patient prognosis, morbidity, and healthcare costs. Compounding the problem is the fact that infections are often caused by events beyond the surgeon's control and can appear weeks to months after the initial procedure. The costs and consequences of implant infections, and prevention and management strategies, are numerous and vary in success. Technological advances are underway to create coatings and other forms of implant surface modification in a manner that imparts some antimicrobial benefit to implant devices. Such coatings can generally be classified based on their mechanism of action: surface adhesion prevention, disinfection, antimicrobial elution, osseointegration promotion, and combinations of the above. Despite multiple advances in the efficacy of these antimicrobial strategies, a major challenge remains ensuring the retention of antimicrobial activity over the postoperative period, a period that has not been satisfactorily resolved to date. However, covering implants with antimicrobial coatings offers the potential to overcome implant-associated infections. For example, antibiotics bound to the metal surface of implants are used to prevent bacterial colonization and biofilm formation. Based on well-defined chemical synthesis, studies have shown that antibiotics can be linked to titanium through a self-assembled monolayer of siloxyamine. The constructed stable metal-antibiotic can resist bacterial colonization and biofilm formation while remaining suitable for osteoblast adhesion and maturation.

[0187] The effects of antimicrobial or antiproteolytic agents, such as chlorhexidine (CHX), on human dentin have been reported in relation to their persistence on oral / dental structures. Persistence refers to the long-term bond between a material (e.g., chlorhexidine) and a substrate (e.g., oral mucosa, oral proteins, dental plaque, dental surfaces). The persistence of CHX is beneficial in its ability to be retained in mineralized and demineralized dentin matrices. Tetracycline also possesses the beneficial property of persistence. While the other antimicrobial agents described need to be evaluated in further studies, persistence is expected to be enhanced, particularly through enhanced surface conditioning of biological substrates and structures and tools optimized for surface conditioning as described in the embodiments herein.

[0188] Bacteria and fungi are capable of communication, transferring contact information between their neighbors, competitors, and hosts. This networking is mediated by small bioactive molecules that are released and received by cells and that direct cellular responses that are essential for their survival in their heterogeneous environments. This intermicrobial signaling plays a role in the microbial world, and further elucidation of these pathways and the molecules involved could impact advances in medical microbiology.

[0189] The global health crisis associated with antibiotic resistance and the urgent need to create new pharmaceutical therapeutic agents is well recognized.

[0190] Antibiotics and microbial chemical mediators may play important roles not only as bacterial weapons to fight competitors, but also as signaling molecules that can regulate the homeostasis of microbial communities in vivo at low concentrations in the prevention and treatment of infectious diseases.

[0191] Many clinically important antibiotics and many other pharmaceutically useful compounds are produced by actinomycetes, primarily of the genus Streptomyces, for example, the antituberculosis antibiotic streptomycin, produced by Streptomyces griseus, and tacrolimus, produced by Streptomyces tsukubaensis, is an important immunosuppressant used to reduce transplant rejection.

[0192] While the adjunctive use of systemic antibiotics alone may provide additional benefits for scaling, root planing, resurfacing, and other medical-mechanical and mechanical debridement procedures, this treatment is not without side effects or adverse reactions attributable to antibiotics or antimicrobial agents. Additionally, the potential emergence of antibiotic resistance in in vivo bacterial flora is a serious concern. Treatment failure can occur due to the inability of the drug to achieve and maintain therapeutic concentrations, particularly at the site of infection. For example, subjects with failed and infected dental implants are susceptible to infections that can spread through bacteria to the rest of the body, and such subjects have traditionally required prophylactic antibiotics before dental procedures. Embodiments may also beneficially assist patients who require pre-treatment for chronic dental implant infections that occur throughout the patient's lifespan, such as primary and secondary infections resulting from dental infections with and without implants, heart murmurs, cardiac valve prostheses, and orthopedic joint prostheses.

[0193] Conceptually, direct application of antimicrobial or antibiotic agents or microbial biomediators to diseased or surgical sites appears to be an attractive therapeutic approach. Additionally, drug or mediator concentrations can be delivered to specific sites at higher doses without increased risk of side effects. Drugs can be given in 100-200 doses above the minimum inhibitory concentration (MIC), thereby eradicating all susceptible bacteria at the site. Localized, site-specific, controlled delivery can be used in conjunction with mechanical debridement procedures in dental scaling and root planing and other surgical procedures, such as bone and hard tissue surgery, implant surgery (e.g., catheters, heart valves, dental implants, prosthetic / artificial joints), and as preventative and interventional therapy throughout an individual's lifespan to maintain and support health.

[0194] Thus, the embodiments described herein may beneficially aid in the prevention and management of infections in medical and surgical treatments, implants involving wounds, and disease sites such as, for example, heart valve endocarditis, orthopedic and spinal catheters.

[0195] As previously described, surface free energy and surface roughness influence bacterial colonization and, therefore, to some extent, affect the implant material and its physicochemical properties. There is a "race for the surface" scenario, i.e., enhanced protein adsorption ultimately results in osseointegration and increased resistance to infection; however, during the early stages of the process, these self-identifying properties may make the implant susceptible to bacterial colonization. While implant infection rates are low, they reflect the surgical technique, the patient's health and age, the physical dimensions and condition of the surgical site, and the medical history of the proposed surgical and implant materials. To minimize infection, with an emphasis on good health, systemic antibiotics are administered preoperatively and for 3 to 14 days postoperatively.

[0196] In an embodiment, the method includes administering a solution comprising 10% urea peroxide to the periodontal pocket of the subject; and / or administering to the periodontal pocket of the subject a solution comprising tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, cipro. and applying a follow-up treatment comprising applying or delivering to the subject's dental treatment an antimicrobial agent consisting essentially of floxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin.

[0197] In embodiments, the method comprises administering a solution comprising 10% urea peroxide to the subject's periodontal pocket; and / or applying or delivering an antimicrobial agent consisting essentially of a topical antibacterial agent, a topical antiviral agent, a topical antifungal agent, a topical antiseptic agent, a topical antimicrobial interaction agent, or a topical antibiotic to the subject's dental treatment.

[0198] In at least one of various embodiments, the patient or their caregiver may be instructed to floss with a gel solution containing urea peroxide at least once daily during the active phase of periodontal disease. The subject may also be instructed to apply other topical treatments directly to the treatment area and tooth roots. For example, the subject or caregiver may be instructed to apply topical fluoride paste (e.g., Prevident®) to the treatment area using their fingers, as opposed to manufacturer-recommended toothbrushes (which only reach the upper surface areas of the teeth and not the roots, particularly between the teeth). The subject may also be instructed to press or apply topical treatments using various interdental brushes, irritants, and floss. These techniques deliver treatments above and below the root surface to control root caries, which has been shown to be caused by bacteria different from caries on the tooth enamel surface to which these treatments are typically applied.

[0199] In one embodiment, a dental treatment method is described that includes providing a gel solution containing 10% urea peroxide for administration to a target treatment area in conjunction with a dental care treatment that employs anesthesia as a standard of care, where the 10% urea peroxide solution anesthetizes the treatment area. The 10% urea peroxide gel acts as a mild topical anesthetic, which, by definition, is a form of anesthesia obtained by applying a drug directly to a mucosal surface. For example, in one embodiment, the 10% urea peroxide solution provides sufficient anesthetic effect to the patient without the need for injectable local anesthetic, where previously dental care treatments required or accommodated injectable anesthesia as a standard of care and / or for patient comfort. One of the most important aspects of dental practice is pain control or elimination. Studies have shown that more patients avoid dental appointments due to pain anxiety than all other reasons combined.

[0200] In embodiments, the portion of the gel solution comprises peroxide gel; and tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, mofetil, thiamin ... A viscous pharmaceutical composition is described that includes a portion containing an antimicrobial agent consisting essentially of a topical antibacterial agent, topical antiviral agent, topical antifungal agent, topical disinfectant, topical antimicrobial interaction agent, or topical antibiotic, including a combination of xifloxacin, norfloxacin, ofloxacin, metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin.In an embodiment, a portion of a gel solution comprising 10% urea peroxide; and tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, Viscous pharmaceutical compositions are described that include a portion containing an antimicrobial agent consisting essentially of a topical antibacterial agent, a topical antiviral agent, a topical antifungal agent, a topical antiseptic agent, a topical antimicrobial interaction agent, or a topical antibiotic, including moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and a combination of minocycline, metronidazole, and ciprofloxacin. In embodiments, the pharmaceutical composition is for the treatment of periodontitis. For example, in embodiments, the pharmaceutical composition is for administration to a subject's periodontal pocket during mechanical debridement treatment.In embodiments, peroxide gels, for example, solutions with 10% urea peroxide, are effective in partial percentages to chemically debride treatment areas for dental treatment; in embodiments, tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, A partial percentage of antimicrobial agents consisting essentially of topical antibacterial agents, topical antiviral agents, topical antifungal agents, topical antiseptic agents, topical antimicrobial interaction agents, or topical antibiotics, including ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, combinations of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and combinations of minocycline, metronidazole, and ciprofloxacin, may make up the remainder of the pharmaceutical product.

[0201] In an embodiment, a dental product is described that includes a dental cleaning device coated with or provided with a solution comprising at least a gel solution containing a peroxide gel. In an embodiment, the gel solution comprises 10% urea peroxide. In an embodiment, the dental cleaning device is selected from the group consisting of a brush and an interdental cleaning device. In an embodiment, the interdental cleaning device is selected from the group consisting of floss, a pick, or an interdental brush. In an embodiment, the interdental cleaning device is a superfloss that includes a sponge provided with at least 10% urea peroxide.

[0202] In another embodiment, the 10% urea peroxide is in a gel solution or partially combined with other medications and applied using an applicator attached to a container holding a proprietary gel solution, such that the applicator is guided into the pocket or area of ​​treatment by the subject or caregiver at a medical, dental, or veterinary clinic or at home, e.g., the applicator has a tip that is a nozzle, tube, spray nozzle, etc.

[0203] In at least one embodiment, tetracycline, vancomycin, daptomycin, gentamicin, ceftriaxone, kanamycin, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin,

[0003] Methods for treating surgical wounds, such as oral surgical wounds or other wounds, are described, comprising administering directly to the wound site being treated a clinically effective amount of a topical antibacterial, antiviral, antifungal, antiseptic, antimicrobial interaction agent, or antibiotic, including combinations of cephalexin, norfloxacin, ofloxacin, metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and combinations of minocycline, metronidazole, ciprofloxacin, and their derivatives. Treatments may include procedures such as bone grafts, surgical membrane placement, connective tissue grafts, tooth extraction sockets, combined periodontal / endodontic treatments, and implant surgery. In at least one embodiment, at least 30-600 mg of pure topical tetracycline, e.g., tetracycline hydrochloride, can be applied directly to the wound site. In at least one embodiment, the tetracycline can be in powder or paste form, or part of a viscous medication, e.g., a gel solution. As will be appreciated, topical tetracycline is used topically, and most of the topical treatment is washed off and therefore not absorbed into the subject's system.

[0204] In embodiments, the present disclosure provides a pharmaceutical formulation for topical dental administration (i.e., oral cavity) comprising at least one of: an antimicrobial compound in an effective amount of 5-90% by weight of the total weight of the formulation; at least one peroxide source compound in an effective amount of 1.5-44% by weight of the total weight of the formulation; and at least one gel agent in an effective amount of 1.0-90% by weight of the total weight of the formulation.

[0205] In embodiments, the pharmaceutical formulation may further comprise at least one carrier, such as excipients such as Krisgel 100™, hydroxyalkylated cellulose and similar compounds, present as a further addition of 1 to 10% by weight relative to the total weight of the formulation.

[0206] In embodiments, the pharmaceutical formulation may further comprise 1 to 10% by weight of at least one additive as a further addition based on the total weight of the formulation, selected from sweeteners (e.g., natural sweeteners such as steviol glycosides or artificial sweeteners such as steviol derivatives, acesulfame potassium, aspartame sucralose, neotame, and advantame), flavors (e.g., mint, peppermint, cherry, or strawberry), colorants, fragrances, preservatives (to extend shelf life and prevent microbial contamination of the formulation), stabilizers, acids (for pH control and balance), bases (for pH control and balance), buffers (for pH control and balance), surfactants (such as steviol glycosides, food-grade surfactants), diluents (such as water, glycerin, propylene glycol), or combinations thereof.

[0207] The terms "further addition," "further added," "further adding," "further additive," and similar terms refer to the act of adding something extra, e.g., adding a further component, additive, or material (i.e., adding an add-on) to an existing intermediate base formulation in excess of or in addition to 100% by weight of the base formulation. The further added element, such as an ingredient or additive, can contribute more than 100% by weight; for example, a further addition of 1-10% by weight can produce a composition or final formulation having 101-110% total weight. The base formulation, including the antimicrobial compound, peroxide source compound, and gel agent, totals 100% by weight, and the further additive can be, for example, one or more components, additives, or materials, or a combination thereof, with or without other further additives. The further additive can be present in or further added to the base formulation, e.g., from about 1 to about 100% by weight, in addition to the 100% by weight base formulation.

[0208] "Peroxide source" and like terms refer to a compound or composition containing a peroxide or peroxide precursor (i.e., a "preperoxide") that can provide or liberate biocidal peroxide species, oxygen species, or both. The peroxide source is preferably inexpensive; stable; safe; and / or commercially available. Peroxide sources can include, for example, hydrogen peroxide, adducts such as urea peroxide, salts such as sodium percarbonate, organic peracids of the formula RC(=O)-O-OH (where R can be, for example, an alkyl substituent having 1 to 10 carbon atoms or an aromatic group, or an aromatic or aryl substituent having 6 to 10 carbon atoms, such as peroxyacetic acid or peroxybenzoic acid), stable organic perperoxides of the formula RC(=O)-OOC(=O)-R (where R can be, for example, an aromatic or aryl substituent having 6 to 10 carbon atoms, such as benzoyl peroxide), stable peresters of the formula RC(=O)-OO-R' (where R can be, for example, an alkyl, aromatic, or aryl substituent having 1 to 10 carbon atoms, and R' can be the same as or different from R), and metal oxides such as zinc dioxide or zinc peroxide (A. Takashi, et al., "Sodium Percarbonate" (SPC) as a Hydrogen Peroxide Source for Organic Synthesis", Chem Letters 1986, Vol. 15, No. 5, pp. 665-666; metal oxides can be a source of peroxides that have biocidal activity when the metal oxide decomposes or dissociates; see "Organic Peroxide" en.wikipedia.org; see Y. Wolanov, et al., "Zinc Dioxide Nanoparticulates: A Hydrogen Peroxide Source at Moderate pH", Environ. Sci. Technol. 2013, 47, 15, 8769-8774). Without wishing to be limited by theory, it is believed that the peroxide source contributes to the effectiveness of the disclosed formulations by generating at least one of free radical species, dioxygen species, oxygenated species, oxygen source species, and similar species, or mixtures thereof.

[0209] In an embodiment, at least one peroxide source compound is urea peroxide. Other names include, for example, urea hydrogen peroxide, urea peroxide, and percarbamide. Urea peroxide is a water-soluble, white, crystalline solid compound or pasty semi-solid composed of hydrogen peroxide and urea. A commercial product known as Glyoxide® (available from prestigebrands.com) contains 10% urea peroxide. The active ingredient in Glyoxide® is 10% urea peroxide. The inactive ingredients in Glyoxide® are citric acid, flavor, glycerin, propylene glycol, sodium lauroyl sarcosinate, and water. Glyoxide® is used as an oral debridement agent and oral wound cleaner. Glyoxide® is also an antiseptic oral cleaner used to treat specific dental problems (such as oral inflammation or wounds) and to improve daily oral hygiene.

[0210] In embodiments, the at least one antimicrobial compound may be selected from any of the antimicrobial compounds previously mentioned, such as, for example, tetracyclines and tetracycline itself, a salt thereof, a prodrug thereof, or a combination thereof.

[0211] In an embodiment, the at least one antimicrobial compound is tetracycline, a salt thereof, or a prodrug thereof, which is 10-40% by weight of the total weight of the formulation.

[0212] In an embodiment, the at least one antimicrobial compound is tetracycline, a salt thereof, or a prodrug thereof, which is 25-30% by weight of the total weight of the formulation.

[0213] In embodiments, the formulation is formulated as a gel, paste, toothpaste, mouthwash, rinse, dental floss coating, chewing gum, oral care strip or film for direct application or adhesion to oral surfaces, lozenge, or combinations thereof, without the need for any Schedule I-V analgesic narcotic.

[0214] In embodiments, the present disclosure provides a method of treating or preventing at least one of bleeding; swelling; pain; receding gums; receding tooth-supporting bone; tooth-supporting bone loss; or a combination thereof in the oral cavity of a subject, comprising applying an effective amount of the disclosed topical dental pharmaceutical formulation comprising at least one peroxide source compound; at least one antimicrobial compound; and at least one gel agent.

[0215] The periodontal tissue is the periodontal attachment apparatus, including the periodontal ligament, which secures the tooth and tooth root to the bone; and the tooth-gingival functional unit, which includes the epithelial and connective tissue attachment of the gums. Both the periodontal ligament and the tooth-gingival functional unit provide biological protection. The attachment applicable to implants is the junctional epithelium to the bone via the gingival tissue, hemidesmosomes, and the implant surface.

[0216] Receding gums, recessed tooth-supporting bone, and loss of tooth-supporting bone mass are examples of what is also known as "clinical attachment loss" or "clinical periodontal attachment loss" of periodontal disease.

[0217] In an embodiment, the present disclosure provides a method of treating oral anatomical structures comprising administering to a patient in need of such administration an effective amount of a topical dental pharmaceutical formulation comprising: at least one antimicrobial compound in an effective amount of 5-90% by weight of the total weight of the formulation; at least one peroxide source compound in an effective amount of 1.5-44% by weight of the total weight of the formulation; and at least one gel agent in an effective amount of 1.0-90% by weight of the total weight of the formulation, wherein at least one symptom is minimized or eliminated compared to the patient without administration of the topical dental pharmaceutical formulation, the symptom being selected from: the patient's bleeding gums; the patient's swelling of the gums; the patient's experiencing pain in the gums or teeth; the patient's gum recession; the patient's tooth-supporting bone recession; the patient's loss of tooth-supporting bone mass; or a combination thereof.

[0218] "Administering," "administration," "administered," and similar terms, such as "treatment," "treating," and similar terms, refer to "contacting" at least the sides or structures of the oral cavity, i.e., the oral anatomical structures of a patient, particularly the teeth and gums, with an effective amount of the disclosed formulations.

[0219] In embodiments, the method of treating an oral anatomical structure may further comprise applying any suitable amount of anesthesia to the root of at least one of the patient's teeth before, during, after, or a combination thereof, administration of the topical dental pharmaceutical formulation. Application of any suitable amount of anesthesia may be accomplished by any suitable manner of contacting the anesthesia with the root of the patient's tooth, such as, for example, direct or indirect methods, such as coating, planing, local gingival injection, and the like.

[0220] In embodiments, the method for treating oral anatomical structures may further comprise topically administering to the patient an effective amount of at least one growth factor-enhanced matrix material (e.g., GEM 21S®) comprising human growth factors and an osteoconductive matrix, wherein the topical administration of the matrix material is accomplished before, during, after, or a combination thereof, administration of the topical dental pharmaceutical formulation. Application of any suitable amount of the at least one growth factor-enhanced matrix material may be accomplished in any suitable topical manner.

[0221] In embodiments, the method of treating oral anatomical structures may further comprise systemically administering to the patient an effective amount of at least one antimicrobial compound, wherein the systemic administration of the at least one antimicrobial compound is accomplished before, during, after, or a combination thereof, administration of the topical dental pharmaceutical formulation.

[0222] In embodiments, bleeding, swelling, pain, or a combination thereof may be minimized.

[0223] In embodiments, bleeding, swelling, pain, or a combination thereof may be eliminated.

[0224] In embodiments, recession of the patient's gums, recession of the patient's tooth-supporting bone, loss of the patient's tooth-supporting bone mass, or a combination thereof may be minimized.

[0225] In embodiments, the recession of the patient's gums, the recession of the patient's tooth-supporting bone, the loss of tooth-supporting bone mass in the patient, or a combination thereof may be reversed or eliminated (i.e., the progression or course of the symptoms of "clinical periodontal attachment loss" is halted or prevented).

[0226] In embodiments, a significant benefit of the disclosed formulations and their administration to subjects in need thereof is minimizing or halting dental caries.

[0227] In embodiments, the step of administering an effective amount of a topical dental pharmaceutical formulation to a patient includes: an amount of formulation administered to a patient in a treatment session (e.g., an amount of formulation sufficient to cover or coat at least one of the following: an active ingredient administered by a trained dental professional or by informed patient self-administration in home care; an amount of formulation sufficient to cover or coat at least one of the patient's anatomical structures: a portion of the patient's gums; a portion of the patient's teeth; a portion of the patient's wound; any portion of the patient's perioral tissues; or a combination thereof); an amount of formulation administered to an oral anatomical structure of a patient with at least one symptom; The duration of agent contact (e.g., initial and subsequent treatment sessions, e.g., 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, etc., of in-clinic patient care, patient home care, or both); patient home care can include, for example, a gel containing the ingredients recited in one or more of the disclosed formulations, and administration of the formulation according to the disclosed methods of treatment); the frequency with which the formulation is administered to the affected patient's oral region (e.g., daily, twice daily, weekly, biweekly, monthly, twice monthly, etc.); the dosage formulation administered, or a combination thereof. Without being limited by theory, it is believed that the effective amount of a topical dental pharmaceutical formulation and the efficacy of treatment with a topical dental pharmaceutical formulation can depend, for example, on the amount of formulation administered in a treatment session, the duration of contact of the formulation with the patient's oral anatomical structures, and the frequency with which the formulation is administered in one or more treatment sessions.

[0228] In embodiments, administering an effective amount of the topical dental pharmaceutical formulation to a patient is accomplished without one or more of general anesthesia, local anesthesia, or an analgesic, i.e., one or more or all of the treatments can be accomplished without one or more of general anesthesia, local anesthesia, or an analgesic because the formulation itself has analgesic properties, i.e., pain relief, for the patient during and after the treatment in the clinic or at home care treatment.

[0229] In embodiments, the method may further include at least one of rinsing the patient's mouth with one or more rinses (e.g., with water or a similar aqueous liquid) to remove excess or residual topical dental pharmaceutical preparation; preventing the patient from swallowing the topical dental pharmaceutical preparation; or both.

[0230] In embodiments, a significant benefit and aspect of the disclosed formulations and their administration to subjects in need thereof is that the disclosed topical treatment methods appear to be free of any allergic reactions in patients.

[0231] In embodiments, administering an effective amount of a topical dental pharmaceutical preparation to a patient provides better wound healing to a patient who has undergone oral surgery compared to a patient who has not received the topical dental pharmaceutical preparation.

[0232] In embodiments, administering the topical dental pharmaceutical formulation to a patient in need of such administration provides synergistic results including one or more of: reduction or halt of gum recession; reduction or halt of tooth-supporting bone recession; reduction or halt of tooth-supporting bone loss; reduction or elimination of bleeding in oral anatomical structures; reduction or elimination of swelling in oral anatomical structures; reduction or elimination of pain in oral anatomical structures; enhanced bone regeneration; enhanced soft tissue repair; or combinations thereof.

[0233] In embodiments, other features of the disclosed evidence of treatment and benefits may include, for example: improved periodontal clinical attachment; reduction of pocket depth through new connective tissue and epithelial attachment; coronal movement of attachment; reversal of gingival recession, particularly over the course of several years of treatment, with coronal movement of the gingival margin; and favorable bone repair as measured by radiographic remodeling. One or more of the disclosed benefits may be available to patients in need of such administration who have problems with their own teeth, gums, and bone support, or to implant patients.

[0234] In embodiments, administering an effective amount of a topical dental pharmaceutical formulation to a patient can provide oral prophylaxis to the patient. For example, for dental patients who have no or minimal oral symptoms but are in a susceptible age group, such as 40-50 years of age or older, or who have a genetic or familial predisposition history, administration of the topical dental pharmaceutical formulation can provide, for example, a reduction or halt of gum recession, a reduction or halt of bone recession, a reduction or halt of bone loss, or a combination thereof. In another example, for dental patients with one or more dental implants, administration of the topical dental pharmaceutical formulation can provide, for example, a reduction or halt of gum recession, a reduction or halt of bone recession, a reduction or halt of bone loss, or a combination thereof. Evidence of these results can be provided, for example, by radiographic results and clinical findings. Additional evidence of these results can be provided, for example, by patient charts and x-ray records showing no further periodontal "attachment loss" or tooth loss. example

[0235] Example 1 Dental preparation 25% gel

[0236] Ingredients: Tetracycline hydrochloride USP 3.75g (each g contains 0.25g or 25%); Polysorbate 80NF 0.3ml (each g contains 0.02ml or 2%); Steviol glycosides 95% powder 0.04g (each g contains 0.00267g or 0.267%); Flavor, peppermint oil 0.3ml (each g contains 0.02ml or 2%); Hydroxyethylcellulose NF (4500-6500cps, 2%, 25c) powder 0.15g (each g contains 0.01g or 1%); and Glyoxide Gel 15g (each g contains 1g or 100%).

[0237] Preparation: 1. Weigh out the relative amounts of tetracycline powder, steviol glycosides, and hydroxyethylcellulose powder; 2. In an appropriately sized beaker, pour approximately 80% of the final volume of Glyoxide® gel; 3. Add the tetracycline powder to the Glyoxide® gel from step 2 and stir with a glass rod to dissolve; 4. Add the polysorbate and flavor to the mixture of tetracycline and Glyoxide® gel from step 3; 5. Add the remaining Glyoxide® gel to the mixture to make up to the final volume, or as needed (QS), to achieve a complete solution at ambient temperature (e.g., 25°C).

[0238] Example 2 Dental preparation 25% gel

[0239] Ingredients: Tetracycline Hydrochloride USP 0.03g (each g contains 0.25g or 25%); Steviol Glycosides 95% Powder 0.1g (each g contains 0.002g or 0.2%); Acesulfame Potassium FCC Powder 0.15g (each g contains 0.00667g or 0.667%); Hydroxyethylcellulose NF (4500-6500cps, 2%, 25c) Powder (each g contains 0.01g or 1%); Flavoring, Pepper - 0.3 ml mint oil (each g contains 0.02 ml or 2%); 0.075 ml polysorbate 20NF liquid (each g contains 0.005 ml or 0.5%); 1 drop food coloring, green (liquid) (each g contains 0.0667 drops or 0.333%); sodium hydroxide 5% (w / v) aqueous solution; and 15 g glyoxide® gel (each g contains 1 g or 100%) (all g and gs added: 19.03 g).

[0240] Preparation: 1. Weigh and combine the solid ingredients: tetracycline, steviol glycosides, acesulfame potassium, and hydroxyethylcellulose, then grind to a fine powder. 2. In an appropriately sized beaker, pour approximately 80% of the final volume of Glyoxide® Gel. 3. Pour the powder from step 1 into the Glyoxide® Gel containing beaker and dissolve the solids by stirring with a glass stir rod. 4. Add polysorbate, food coloring, and flavoring to the beaker. 5. Add the remaining Glyoxide® Gel to the mixture to make up to the final volume, or as needed (QS), to achieve a complete solution at ambient temperature (e.g., 25°C). The pH should be approximately 3.5-6.0. The pH can be adjusted using 5% aqueous sodium hydroxide. The pH should be tested after each drop of aqueous sodium hydroxide is added.

[0241] Example 3 Dental preparation 25% gel

[0242] Ingredients: Tetracycline Hydrochloride USP 3.75g (each g contains 0.25g or 25%); and Glyoxide® Gel 15g (each g contains 1g or 100%) (all g and gs added: 18.75g).

[0243] Preparation: 1. Weigh out tetracycline and grind to a powder. 2. In an appropriately sized beaker, pour approximately 80% of the final volume of Glyoxide® gel. 3. Pour the tetracycline powder into the Glyoxide® gel containing beaker and dissolve the solids by stirring with a glass stir rod. 4. Add the remaining Glyoxide® gel to the mixture to make up to the final volume, or as needed (QS), to achieve a complete solution at ambient temperature (e.g., 25°C).

[0244] Example 4 Dental (viscous) 25% gel

[0245] Ingredients: Tetracycline Hydrochloride USP 3.75 g (each g contains 0.25 g or 25%); Krisgel 100™ Gel 1 ml (each g contains 0.0667 ml or 6.67%); and Glyoxide® Gel 15 g (each g contains 1 g or 100%) (all g and g added together: 18.75 g).

[0246] Preparation: 1. Weigh out and grind tetracycline to a powder. 2. In an appropriately sized beaker, pour approximately 80% of the final volume of Glyoxide® gel. 3. Pour the tetracycline powder into the Glyoxide® gel containing beaker and dissolve the solids by stirring with a glass stir rod. 4. Add the Krisgel to the mixture and mix thoroughly. 5. Add the remaining Glyoxide® gel to the mixture to make up to the final volume, or as needed (QS) to achieve a complete solution at ambient temperature (e.g., 25°C).

[0247] Example 5 Patient #1 This patient was treated with any of the formulations in Examples 1-4 above, or a combination thereof, according to the disclosed chemical curettage method, with the following results:

[0248] Reduction or cessation of further gum recession and regeneration of new gum tissue during Phase I periodontal therapy through the use of the disclosed chemical curettage method and the use of the disclosed topical antimicrobial gel formulation.

[0249] Strengthening and augmentation of new periodontal tooth-supporting periodontal tissue with enhanced regeneration of new periodontal attachment organs, accompanied by a reduction in periodontal probing depth to a more normal probing sulcus depth of 1-3 mm, without bleeding on periodontal probing of the sulcus.

[0250] Phase II periodontal surgery on the left mandibular first molar and second premolar followed by an increase in new periodontal tooth-supporting bone with enhanced regeneration of bone and new periodontal attachment apparatus, accompanied by a reduction in periodontal probing depth to a more normal probing sulcus depth of 1-3 mm, without bleeding on periodontal probing of the sulcus.

[0251] Increased tooth-supporting bone mass.

[0252] Reduction and elimination of bleeding in oral anatomical structures related to periodontium.

[0253] Elimination of swelling of oral anatomical structures related to periodontal tissues.

[0254] Elimination of pain sensation in oral anatomical structures during procedures using topical antimicrobial gel formulations, including anesthetizing tooth roots during scaling and root planing.

[0255] Enhanced bone regeneration following the method and use of a topical antimicrobial gel formulation.

[0256] Enhanced soft tissue repair.

[0257] Complete restoration of periodontal health.

[0258] The above results were supported by radiological images (see, for example, Figures 5A and 5B; not all others are shown). Therapist's description: Following infiltration anesthesia with 2% xylocaine 1:100,000 epinephrine (1 1 / 2 capsules) (without mandibular block), bone surgery was performed on teeth #19-medial and #20-distal, mostly interdentally. In #19-medial, bone defect debridement and root planing to the root tip were performed, and root planing was also performed on #18-D, with topical antimicrobials used on both. Severe two-walled BL craters (buccolingually) were noted on the proximal surfaces of teeth #18-19, with furcations noted mid-root and Gem to the top of the apical wall. Filled with 21S®, #20-distal, bone apical 1 / 3, wide wall 3; mostly #19-medial; filled to the apex using Gem21S®, used two interrupted mattress sutures (not one) to attempt primary closure, periodontal dressing, and written and verbal postoperative instructions. Doxycycline already prescribed, one Motrin 600 mg tablet prescribed as needed (prn). Administered "PO" (orally) for pain, and prescribed Peridex.

[0259] Example 6 Patient #2: This patient was treated with any of the formulations in Examples 1-4 above, or a combination thereof, administered according to the disclosed chemical curettage method with the following results:

[0260] During Phase I periodontal treatment, further gum recession was reduced or halted, and overall gingival tissue regeneration was achieved. Peri-implantitis was treated due to the patient's complaint of severe pain for at least 10 months. An oral surgeon placed an implant in the left mandibular molar region, and a general dentist placed a crown. Initial examination by a curettage specialist revealed a non-effusion fistula, but the patient presented with "jaw pain on the right side of the face, popping sounds when opening and closing the mouth, and pain extending to the left temporomandibular joint" as well as the right side of the face in the right temporomandibular joint capsule. Patient #2's past dental history for ongoing implant abscess treatment included receiving systemic antibiotics three times in the previous 10 months for pain and swelling, with recurrence of clinical signs and symptoms. Patient #2's past dental history included teeth grinding and smoking 8 to 10 cigarettes per day. An initial clinical examination by the curettage specialist revealed intraoral swelling, suppuration, and an acute abscess, as well as acute swelling and a 2mm fistula on the distal-facial aspect. Patient #2 also reported "white pus erupting and then draining." Patient #2 had generalized moderate to severe periodontitis, but the abscessed implant site required immediate emergency care and had a long history of severe pain corresponding to the location of a previous extraction of the left mandibular first molar and placement of a crowned implant. At the second visit, 19 days after the initial examination, the patient reported a hard object in the gums on the facial side of the mandibular left first molar implant site. Patient #2 did not recall having any food or material lodged under the gums on the facial side. A topical medicinal gel formulation selected from Examples 1-4 above was administered into the pocket, and the area was anesthetized. The curettage specialist palpated the hard object, removed it, and sent it to the pathology laboratory. Along with limited occlusal adjustments with selective grinding on the implant and opposing teeth, within a few hours of the second visit, patient #2 unexpectedly noticed complete relief of pain in his face and jaw for the first time in the past 10 months.

[0261] Patient #2 also noted an increase in new periodontal tooth and implant supporting clinical attachment of combined connective tissue and long junctional epithelium, accompanied by enhanced regeneration and new periodontal attachment apparatus, with no bleeding on periodontal probing in the sulcus at the site of failed implant #19, and a reduction in periodontal probing pocket depth to a more normal probing sulcus depth of 1-3 mm following removal of the osteonecrotic debris. The pathology report after removal of a nonviable osteonecrotic fragment of lamellar bone (approximately 0.6 x 0.2 x 0.1 mm, tan in color, irregular in shape, submitted as a single block) noted loss of bone cells from the bone lacuna, peripheral resorption, and bacterial colonization.

[0262] The previous 8 mm pocket depth on the facial side of the mandibular left first molar site implant was now 3 mm, with no bleeding on periodontal probing, no facial swelling, and no pain anywhere on the patient's face or jaw. The implant's pain on percussion was alleviated at the second visit with selective grinding and occlusal adjustment with the application of a topical gel formulation. Patient #2 reported being pain-free almost immediately from the second visit until his most recent third treatment visit (approximately 50 days after the second examination visit). No local anesthesia or pain medication was recommended or required for Patient #2.

[0263] Loss and cessation of tooth-supporting bone mass.

[0264] Reduction and elimination of bleeding in oral anatomical structures related to periodontium.

[0265] Elimination of swelling of oral anatomical structures related to periodontal tissues.

[0266] Elimination of pain sensation in oral anatomical structures during procedures using topical antimicrobial gel formulations, including anesthetizing tooth roots during scaling and root planing.

[0267] Methods and enhancement of soft tissue repair following use of a topical antimicrobial gel formulation.

[0268] The above results were supported by radiological images (not shown).

[0269] Example 7 Patient #3 This patient was treated with any of the formulations in Examples 1-4 above, or a combination thereof, according to the disclosed chemical curettage method, with the following results:

[0270] Patient #3 initially presented with the chief complaints of "visible gaps in the upper front teeth, movement of all upper right teeth, gum recession, and sensitivity to cold." Patient #3 reported that he began clenching his teeth during the onset of his COVID-19 infection period. Patient #3 reported heavy mouth breathing. Patient #3 reported recently starting to use an electric toothbrush three times per day and floss all teeth in the morning. Patient #3 has used a Waterpik approximately three times per week for several years. Patient #3's comprehensive periodontal examination included findings of generalized periodontal pockets measuring 5 to 8 mm deep. Generalized gum recession and increased tooth mobility, particularly in the maxillary and mandibular incisors, were noted. The diagnosis was one of severe periodontitis of multiple incisors, particularly the maxillary central incisors, with pathological migration and occlusal trauma. Full mouth radiographs provided by Patient #3's general dentist showed progressive periodontal bone loss and tooth movement, and increasing gap formation in the incisors. Full mouth radiographs by Patient #3's general dentist were obtained at 3 intervals over a 6-year period (not included).

[0271] Phase I treatment involved administering any of the above gel formulations of Examples 1-4 according to the disclosed methods over five or more visits over a period of five to six months, consisting of an initial periodontal evaluation and diagnosis; in-person preventive dental care training; five visits for formulation administration and procedures described for scaling and root planing; occlusal (bite) adjustments; and periodontal health reassessment. Phase I was completed after three months.

[0272] Phase II treatment included periodontal surgery as needed to restore periodontal health and resolve any remaining areas with persistent edema, bleeding on periodontal probing, altered gingival architecture, and significant pocket depth and pocket type (e.g., 4 mm or greater; in combination with gingival, periodontal, or subbony defects). Pockets demonstrated clinical signs of active periodontal disease. Phase II treatment was continuous, and 3 months and 10 days after completion of Phase I, the patient selected and completed periodontal surgery on the maxillary right quadrant only, as well as on the maxillary left incisors and canines to address the above-mentioned chief complaint of Patient #3.

[0273] The above results were supported by radiographic images (not shown). Initial radiographs of the maxilla and subsequent radiographs of the mandibular incisors 6 months later showed favorable changes in crestal bone height and bone density. Radiographic and clinical analysis also showed no further gingival recession. Periodontal probing depths were within the normal 1-3 mm range, with new bone formation, new periodontal attachment apparatus, new connective tissue, and new epithelial attachments, and no clinical signs of active periodontal disease. Closure of the dental space between the maxillary central incisors was also visible both radiographically and clinically, which was related to the chief complaint of Patient #3.

[0274] Example 8 Patient #4 Patient #4 presented for periodontal care and the first comprehensive periodontal examination. Patient #4's chief complaint was "intermittent bleeding gums, tooth movement, and sensitivity to cold."

[0275] Patient #4 reported grinding or clenching his teeth during the day, which contributed to the tooth mobility and supported the report of tooth movement. The teeth were significantly mobile overall, with some appearing to have a bleed-out prognosis. Overall, pocket depths ranged from 7 to 8 mm, with generally severe bleeding on probing. The maxillary incisor and periodontal pockets were 8 to 9 mm deep.

[0276] Patient #4's periodontal symptoms included chronic inflammatory disease with gingival hyperplasia and swelling. Patient #4 had an anterior open bite and adult tongue protrusion. Patient #4 had previously smoked 1.5 packs of cigarettes per day for 13 years, although he had quit smoking two years earlier.

[0277] Approximately 3 months after the first examination date, a full-mouth intraoral radiograph was obtained (not shown).

[0278] The periodontal diagnosis for patient #4 was confirmed as generalized severe periodontitis with primary and secondary occlusal trauma.

[0279] Patient #4 was treated with any of the formulations of Examples 1-4 above, or a combination thereof, administered according to the disclosed chemical curettage method.

[0280] At Patient #4's first Phase I treatment appointment, approximately 4 months after the first examination date, during scaling and root planing with topical antimicrobial gel, significant, severe, and intense inflammation of the gums was observed, accompanied by severe, profuse bleeding during scaling and root planing. Topical and systemic antimicrobials were applied and prescribed for immediate use. Photographs of the oral cavity were taken.

[0281] Patient #4 returned 12 days later and had much less bleeding during periodontal probing and scaling and root planing. Patient #4's clinical signs of inflammation throughout the periodontal tissues were much less, and the patient was very aware of this significant improvement. Photographs were also taken for comparison with the first visit. This time, it was clear that the bleeding intensity was much less.

[0282] Patient #4's next three visits were staggered over a period of approximately 72 days. Further improvement was noted during the first of these three visits as the periodontal treatment progressed, but less improvement was noted during the following two visits. The therapist hypothesized that Patient #4 may have an underlying medical condition affecting his healing rate and tissue repair. The therapist consulted with Patient #4's physician to perform clinical and laboratory tests, including metabolic testing, to help determine whether there was a systemic medical condition that affected the oral findings and the severity of his active periodontal disease. Patient #4's physician's examination confirmed a systemic illness, including hypothyroidism and diabetes with elevated blood sugar levels. Given these medical findings, the therapist recommended that Patient #4 seek immediate medical care for his condition, as oral modifications and planned periodontal therapy could increase the likelihood of improvement and complete restoration of periodontal health. The therapist planned to see Patient #4 every three months for Phase III periodontal maintenance for the foreseeable future while Patient #4 remains under the physician's care.

[0283] The ongoing interim treatment results for patient #4 are summarized below.

[0284] Reduction or cessation of further gum recession and significant reduction in bleeding on periodontal probing and scaling and root planing, although there was no complete elimination of bleeding on periodontal probing in the molar teeth where the periodontal pocket depths had now been reduced to a depth of 5-6 mm.

[0285] Increase in new periodontal attachment apparatus of the teeth without bleeding on periodontal probing of the sulci, with a general reduction in periodontal probing depth to more normal probing sulci of 1-3 mm, except for the left maxillary and mandibular first and second molars and the maxillary right first and second molars, where the periodontal probing depth was 5-6 mm.

[0286] Reduced bleeding of oral anatomical structures related to periodontal tissues.

[0287] Elimination of swelling of oral anatomy related to periodontal tissues. Reduction of gingival edema and congestion with establishment of better tissue tonicity for future surgical management, if necessary, as part of Phase II periodontal therapy.

[0288] Elimination of pain sensation in oral anatomical structures during procedures using topical antimicrobial gel formulations, including anesthetizing tooth roots during scaling and root planing.

[0289] Enhanced regeneration of healthy periodontal tissue following the method and use of a topical antimicrobial gel formulation.

[0290] Enhanced soft tissue restoration or a combination thereof and restoration of periodontal health for most of Patient #4's teeth.

[0291] Example 9 Patient #5 Patient #5 presented to a second clinic for first periodontal care and a first comprehensive periodontal examination. Patient #5 reported a chief complaint of "bleeding gums, sensitivity, and teeth that felt cold, hot, 'sweet,' and sensitive to metal." Patient #5 had previously undergone periodontal therapy using scaling and root planing by a first periodontist specialist at a different first clinic four years prior. Patient #5 also reported that "the general dentist later used a laser to treat the periodontal disease, which was very painful."

[0292] Patient #5 reported daytime bruxism and jaw clenching (which may contribute to the tooth mobility pattern) and reported that his teeth were moving. An occlusal night guard was recommended to help mitigate destructive forces that could exacerbate tooth mobility and potentially act as co-destructive forces, accelerating periodontal bone loss. Patient #5's teeth were generally significantly mobile, with some, particularly the maxillary incisors, appearing to be in a dire state. Overall, pocket depths ranged from 7 to 8 mm, with generally severe bleeding on probing. The maxillary incisors had periodontal pockets ranging from 6 to 9 mm deep. Furcation involvement was noted on teeth #3, #14, #30, and #31. Tooth mobility patterns also increased, becoming significantly more severe on teeth #12, #13, and #14. Other teeth were also mobile, but to a lesser extent. Along these deeper pocket depths there was generalized periodontal bleeding on probing and heavy buildup of calculus and biofilm.

[0293] Occlusal analysis showed a Class II angular relationship with a 7mm overbite and zero overjet. The incisors had immature centric occlusion contacts, and patient #5's years of clenching and grinding contributed to their mobility, movement, and pathological migration.

[0294] Patient #5's periodontal symptoms indicated a chronic inflammatory disease with gingival hyperplasia and swelling of the gums. Patient #5 had "smoked only one pack of cigarettes per week for over 30 years." Patient #5 "had nightmares about his teeth falling out." Patient #5 noticed dental caries and realized the need for root canal treatment on his lower right second molar. Patient #5 also had caries in other teeth that needed to be treated.

[0295] A full-mouth intraoral radiograph was taken 12 days after the first visit.

[0296] The periodontal diagnosis for patient #5 was confirmed as generalized severe periodontitis with primary and secondary occlusal trauma.

[0297] At Patient #5's first Phase I treatment appointment, 49 days after the first visit, it was observed that during scaling and root planing with the disclosed topical antimicrobial gel, there was a significant amount of severe, intense inflammation in the gums with severe, profuse bleeding during scaling and root planing. A topical and systemic antimicrobial was applied and prescribed for immediate use during scaling and root planing, followed by systemic application over the next 7 days.

[0298] Patient #5's next visit was 285 days after the first visit, and there was much less bleeding during periodontal probing and scaling and root planing. Clinical signs of inflammation throughout the periodontal tissues were much less, and the patient was very aware of this significant improvement. New photographs were taken (not included) for comparison with the first visit to document the significantly reduced intensity of bleeding.

[0299] Patient #5's next three visits, alternated over a period of approximately 72 days, documented further improvement with the progression of periodontal treatment, although these subsequent visits showed less improvement than expected. The therapist hypothesized that Patient #5 had an underlying medical condition that could be affecting his healing rate and tissue repair. The therapist consulted with Patient #5's physician to perform clinical and laboratory tests, including metabolic testing, to help determine whether there was any systemic medical disease that was affecting the oral findings and the severity of his active periodontal disease. Patient #5's physician's examination confirmed systemic disease, including hypothyroidism and diabetes with elevated blood sugar levels. Given these medical findings, the therapist recommended that Patient #5 seek immediate medical care for his condition, as oral modifications and planned periodontal therapy could increase the likelihood of improvement and complete restoration of periodontal health. The therapist planned to see Patient #5 every three months for Phase III periodontal maintenance for the foreseeable future while Patient #5 remains under the physician's care.

[0300] Treatment of Patient #5 with any of the formulations of Examples 1 to 4 above was accomplished according to the disclosed chemical curettage method, providing the following recited results for Patient #5:

[0301] Reduction or cessation of further gum recession and new regrowth of firmer, healthier gum tissue without swelling, inflammation, or edema.

[0302] Enhanced opportunity for bone regeneration and an increase in new periodontal tooth-supporting periodontal tissue with an overall new periodontal attachment apparatus, accompanied by a reduction in periodontal probing depth to a more normal probing sulcus depth of 1-3 mm, and no bleeding upon periodontal probing of the sulcus.

[0303] Increased bone mass and halt of tooth-supporting bone loss, and new attachment of connective tissue and epithelial attachment to the root surface, restoring 1-3 mm of healthy periodontal sulcus.

[0304] Resolution of bleeding in oral anatomical structures associated with periodontal tissues, with restoration of healthy periodontal tissues.

[0305] Resolution of swelling of oral anatomical structures related to periodontal tissues. Gingival edema and congestion were reduced by repeating Phase I periodontal therapy, involving scaling and root planing and repeated application of topical antimicrobial gel, periodically in all four quadrants of Patient #5's mouth, six times over the next five months, according to the described formulation and method. This repeated approach was discontinued as necessary in each remaining active periodontal disease pocket site that had not yet recovered to a 1-3 mm sulcus, throughout the course of an additional five to six months of Phase I periodontal therapy. Each treatment visit with the disclosed formulation and method restored health with minimal or no periodontal tissue loss, while establishing better tissue tone for possible additional surgical work. At the final reevaluation of Phase I periodontal treatment, the maxillary incisors and canines were carefully examined.

[0306] Elimination of pain sensation in oral anatomy during procedures, including anesthetizing tooth roots during scaling and root planing, using a topical antimicrobial gel formulation.

[0307] Enhanced bone regeneration following the use and application method of a topical antimicrobial gel formulation.

[0308] Enhanced soft tissue repair and restoration of periodontal health.

[0309] Reduction and elimination of bleeding in oral anatomical structures related to periodontium.

[0310] Resolution of swelling of oral anatomical structures related to periodontal tissues. Treatment with the disclosed formulations and methods reduces gingival edema and congestion, accompanied by less periodontal tissue loss and recession, along with establishing better tissue tone for better surgical handling. This Phase I approach has been shown to be predictable, with any necessary periodontal plastic surgery regeneration procedures and GEM21S® bone graft material conditionally followed in Phase II periodontal therapy. Phase II periodontal surgery was typically performed conditionally on the maxillary arch only. However, periodontal surgery may still need to be performed on multiple teeth in the mandibular incisor-canine region. If the need for corrective periodontal surgery remains, re-evaluation is assessed at future Phase III periodontal maintenance visits.

[0311] As described below, widespread in vivo administration of viscous tetracycline antimicrobials and solutions containing 10% urea peroxide, such as Glyoxide®, together provided enhanced treatment, healing, and management of gum disease, including advanced periodontal disease. As will be appreciated, the length of time for treating periodontitis in its maintenance phase can be, for example, lifelong, similar to diseases such as diabetes. Thus, the treatment population included thousands of subjects monitored for over 30 years to confirm the effectiveness of treatment. Each subject may have up to six or more documented pocket sites and up to 32 records of teeth and other periodontal disease parameters and health records in their patient records. Treatment was applied repeatedly throughout the course of Phase I, Phase II, and Phase III treatment, without complications (e.g., true allergic reactions). Patients reported no adverse issues and used these products primarily at home daily as part of their oral hygiene routine. Complaints about tetracycline paste in the clinic were related to taste, not pain, and patients rinsed the paste off with tap water in a cup and continued their chemotherapy treatment routine during treatment.

[0312] During Phase I treatment of periodontitis, a gel solution containing 10% urea peroxide was applied directly to the periodontal pockets and pocket areas, and immediately after or before, 30 to 600 mg or more of pure topical tetracycline in powder or paste form was also applied directly to the pockets and pocket treatment areas along with the gel solution. The gel solution and tetracycline were also applied directly to the teeth. Tetracycline was added at intervals throughout the treatment. Treatment was performed for pockets from 3 mm to 10 mm and deeper.

[0313] When the pocket tissue was swollen, 10% urea peroxide was penetrated into the deep pockets below the gum line. The 10% urea peroxide was in the form of a viscous gel and applied to the wound site or pocket using a periodontal probe, for example, or a curette or scaler. For example, one or two drops from a squeeze bottle applicator was applied to the tip of a curette or the end of a scaler, or using periodontal pocket measurement probing. Peroxide gel was also applied under artificial teeth and implants, whether implants or natural teeth, and under restorative bridges, such as the pontic area. As described above, peroxide was found to be effective as an anesthetic, even when applied as little as one or two drops to the treatment area, allowing for deeper mechanical debridement during the procedure without the need for additional anesthesia. Tray application was also not required.

[0314] This beneficial effect was enhanced by the use of mechanical debridement tools with optimized cutting edges. For example, sharpening tools that optimize the blade angle are described in U.S. Patent Nos. 6,074,293, 6,361,408, and 6,949,018, U.S. Patent Application No. 15 / 241,252, and International Patent Application No. PCT / US2015 / 041998, each of which is incorporated herein by reference in its entirety. Sharpening the working edges of dental tools, such as curettes and other scalers, prior to treatment further reduced the need for anesthesia. A sharp, polished cutting edge reduces the torque and pressure required on the tooth root, reducing the likelihood of slippage. Mechanical debridement could be performed on subjects without other topical anesthesia, such as lidocaine, or injectable forms of anesthesia (e.g., novocaine), and tool penetration into the pocket and instrument well was significantly greater than 5 mm, reaching 7-10 mm or greater.

[0315] It has been found that when administered in conjunction with appropriately sharpened cutting tools, the root surface can be smoothed to 1–5 microns, down to 1 micron. Root preparation to this degree of smoothness renders the root unviable for bacteria and pathogens because bacteria are unable to attach to it. Thus, chemical debridement with gels has made it possible to treat pockets nonsurgically, without surgery, to depths of 5 mm and deeper than 10 mm for instrumented wells. Repeated treatments over 4–6 months or longer, as needed, allow for gradual reduction in pocket probing depth due to proliferation and reattachment of epithelial and fibroblast cells. Minimal gingival recession was also recorded during the healing and long-term Phase III maintenance periods, even over years or a lifetime.

[0316] Chemical debridement of the pocket site soft tissue walls and root surface preparation using agents such as tetracycline with viscous peroxide gel were observed to allow for more rapid and thorough root planing enhancement. Findings included enhanced wound repair with new soft tissue attachment to the root surface and a gradual reduction in pocket depth, with pockets over 10 mm reduced to only 1–3 mm over the course of therapy without surgical intervention. Probing pocket depths that appeared hopelessly advanced at the start of treatment were reduced with reduced tooth mobility, making limited surgical intervention manageable when necessary. Furthermore, follow-up use of 10% urea peroxide gel at home by patients, as per treatment guidelines, aided in biofilm control and chemical curettage of the pocket site, reducing pocket depth to control biofilm regrowth and, therefore, clinical inflammatory disease.

[0317] Tetracycline has also been applied to the treatment area using a periodontal probe or curette, or in some cases, directly into the pockets and surrounding tissues from a capsule or medicine dish during mechanical root planing and scaling. Tetracycline was administered as a full-strength powder or paste of pure topical tetracycline. Tetracycline was placed on the curette by moistening the cutting edge of the curette with sterile saline and placing the moistened curette tip into a plastic medicine cup containing tetracycline powder, allowing it to adhere to the curette tip. For peroxide gel and 10% urea peroxide gel, the viscous solution was picked up simply by placing the curette in a plastic medicine cup containing the peroxide gel. Various other surgical instruments have been used in a similar manner, for example, periosteal scrapers at tooth extraction sites. In the case of powders, 30 to 600 mg (milligrams) or more of tetracycline HCl powder was used during the course of nonsurgical treatment, depending on the number and severity of the pockets being treated. Careful sterilization procedures allowed the caregiver to place tetracycline into a medicine cup approximately 20 ml in size, but much smaller doses of the medication were used. Tetracycline was present in the treatment area for up to 10 minutes or longer during mechanical (and chemical) debridement. Tetracycline was not used in irrigation; therefore, it was diluted only through the subject's gingival crevicular fluid and that present in the debridement peroxide solution, which was sufficient to give the tetracycline a paste-like consistency when applied. When topical tetracycline was used topically, most of the topical treatment was washed away after treatment.

[0318] Based on the treatments described herein, tetracycline is believed to kill bacteria, soften the primarily bacterial biofilm, and help condition and clean the tooth root. During mechanical debridement, a high-pitched ringing sound was heard as the tooth was worked. The tooth literally became clean with a high-pitched ringing sound. The combination of a gel solution containing 10% urea peroxide and viscous tetracycline biologically cleansed the treatment area, including the tooth root. The peroxide gel solution and antimicrobial agent are believed to perform a "chemical curettage" to remove toxins and bacteria that normally adhere and reattach to the tooth root, remove inflamed or diseased tissue, remove foreign pathogens, and remove foreign and extraneous material trapped in the tooth, such as food particles. As noted above, tetracycline was not used with a irrigation and was therefore in a viscous or paste-like form when applied to pockets to a depth of 10 mm or more. Because biofilms can increase with gingival crevicular fluid and more fluid, the use of powders, pastes, or other low aqueous viscosity forms of tetracycline may be beneficial in periodontal therapy and reduce the disease threshold.

[0319] Additionally, the majority of subjects, even those with severe periodontitis, reported no visible bleeding during rinsing and reduced tenderness. Glyoxide® gel is believed to cause dissolution of blood, blood products, and inflammatory exudates found in the periodontal pockets, producing a visible "white foam," which patients preferred to see during rinsing rather than expelling visible blood onto the cuspidor of the dental chair. After using 10% urea peroxide gel as instructed and following the oral hygiene patient home care protocol, patients reported that their gums were no longer bleeding by the second treatment appointment.

[0320] After treatment, subjects had favorable pocket depth reduction through tissue reattachment, re-epithelialization, fibroblast repopulation at the infected site, collagen fiber regrowth, new bone proliferation, pocket depth reduction, and favorable wound healing, with healing evident during the active phase of the disease.

[0321] During the active phase of the disease, treatment was repeated multiple times. For Phase III maintenance visits, the preferred frequency was every three months after the initial active Phase I and Phase II treatments. No true allergic reactions were observed in the patient population due to topical use of tetracycline or 10% urea peroxide gel. For example, tetracycline was used in all office dental procedures, both postoperative and nonoperative, either in conjunction with peroxide gel or applied separately on different days. When applied to extraction sockets or pockets or dental implant sites, patients reported no bleeding, little to no pain, no swelling, and rapid healing without morbidity or complications. Motrin® and Tylenol were used exclusively as analgesics during the procedure as needed. Subjects also experienced cessation of bone loss and, in some cases, a 90% improvement in bone regeneration. Patients also experienced, among other patient findings, enhanced gingival repair and comfort, and elimination of bleeding on probing. Clinically, migration of the epithelial attachment to the crown of the tooth may also be observed. Patients whose teeth initially showed radiological evidence of as much as 90% bone loss have been routinely treated with high success rates and lifelong tooth retention.

[0322] Management of tooth mobility in these cases of advanced periodontal bone loss consists of reducing tactile vibration and centric occlusion immaturity and pursuing group function. Minimizing occlusal trauma, whether primary or secondary, aids in healing and repair of periodontal tissues.

[0323] Additionally, 10% urea peroxide gel and tetracycline treatments were administered as needed in conjunction with the Phase II treatments described herein, including endodontic-periodontal lesions with concurrent root canal therapy, extractions, implants, etc.

[0324] Additionally, 10% urea peroxide gel and tetracycline treatment was administered after both non-surgical (Phase I) and surgical treatment (Phase II) in conjunction with a maintenance phase (Phase III).

[0325] Treatment was applied using a mechanical debridement tool with a cutting edge that was optimized, for example, using the sharpening tools described in U.S. Patent Nos. 6,074,293, 6,361,408, 6,949,018, U.S. Patent Application No. 15 / 241,252, and International Patent Application No. PCT / US2015 / 041998, each of which is incorporated herein by reference in its entirety.

[0326] The oxidizing and foaming effects of urea peroxide gel have been found to flush away dead and live cells. It is believed to help create or maintain an aerobic environment in periodontal tissues. Because urea peroxide is not acidic, it is believed to avoid the need for traditional acidic agents that can be used to kill and flush away necrotic or unwanted tissue, but which can also damage enamel and cementum.

[0327] One advantage of peroxide gel used with pure viscous tetracycline is that debridement occurs with minimal aqueous or liquid dilution, which advantageously enhances the therapeutic effect and results in "chemical curettage" that enhances mechanical debridement, root planing, and scaling, and root surface preparation and removal of diseased granulation tissue in and around the pocket walls. During enhanced root planing, whether during Phase I, Phase II, or Phase III treatment using peroxide gel, there was little or no visible red blood in the mouth due to inflammation and infected tissue. This is thought to be due to the release of red blood cells, immune-inflammatory cell types, and the breakdown of blood clots due to degenerative epithelial changes in the periodontal pocket walls in chronic destructive periodontitis.

[0328] The application of the disclosed topical antibacterial, antiviral, antifungal, disinfectant, antimicrobial agent, and antibiotic is believed to have a similar effect to tetracycline by direct topical application to the site in a viscous form.

[0329] Tetracycline and doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, amoxicillin and clavulanic acid combinations, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifen The combination of loxacin, norfloxacin, ofloxacin, metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and the combination of minocycline, metronidazole and ciprofloxacin act as systemic antibiotics and are believed to produce multiple beneficial effects in periodontal tissues without their systemic administration and in accordance with the present disclosure.

[0330] Similarly, each of the topical antibacterial agents, topical antiviral agents, topical antifungal agents, topical antiseptic agents, and topical antimicrobial interaction agents is considered to act as a topical bacteriostatic or bactericidal agent in accordance with the present disclosure.

[0331] The flow of intracervical fluid, which naturally circulates the viscous tetracycline, may improve healing without overly diluting its antibiotic effect on the treated area. Tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, metronidazole Topical antibacterial, antiviral, antifungal, antiseptic, antimicrobial, and antibiotic agents, including combinations of cefaxil and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and minocycline, metronidazole, and ciprofloxacin combinations, are also thought to kill bacteria in the pocket and are also thought to have a fast-acting effect since the pocket wall tissue looks different immediately after use.One guess is that tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, Topical antibacterial, antiviral, antifungal, antiseptic, antimicrobial, and antibiotic agents, including loxacin, ofloxacin, combinations of metronidazole and amoxicillin, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and combinations of minocycline, metronidazole, and ciprofloxacin, have beneficial effects on tissue proteins, which may contribute to advanced healing. Tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, amoxicillin and clavulanic acid combinations, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin Topical antibacterial agents, topical antivirals, topical antifungals, topical antiseptics, topical antimicrobial agents, and topical antibiotics, including fluoxacin, ofloxacin, metronidazole and amoxicillin combinations, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, and minocycline, metronidazole and ciprofloxacin combinations, may contribute to an aerobic environment hostile to anaerobic pathogens.

[0332] The topical antimicrobial effect of tetracycline when applied as a viscous agent is also believed to be useful in preventing implant failure through early recognition and intervention of peri-implant disease. Additionally, the use of viscous peroxide, e.g., 10% urea peroxide, by the patient as a co-therapist similarly prevents implant failure. In the case of implants, viscous tetracycline is applied around the implant and "painted" into the pocket, creating a treatment similar to that in the case of periodontitis, involving treatment of natural teeth and periodontitis using a periodontal probe, whether in Phase I, Phase II, or Phase III.

[0333] Tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, a combination of amoxicillin and clavulanic acid, clavulanic acid, metronidazole, ciprofloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, a combination of metronidazole and amoxicillin Other possible beneficial effects of the use of topical antibacterial, antiviral, antifungal, antiseptic, antimicrobial, and antibiotic agents, including cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cephalexin, cefepime, ceftriaxone, or combinations of minocycline, metronidazole, and ciprofloxacin, are due to demineralization of the dentin surface, removal of the smear layer, additional beneficial effects on cementum, exposure of dentinal tubules, and reduced tissue destruction, all of which result in improved periodontal regeneration.

[0334] Although this disclosure has been described with reference to various specific embodiments and techniques, many other variations and modifications are possible while remaining within the scope of this disclosure.

Claims

1. 1. A pharmaceutical formulation for wound debridement comprising: an effective amount of at least one antimicrobial compound in an amount of 5 to 90% by weight of the total weight of the formulation; an effective amount of at least one peroxide source compound in an amount of 1.5 to 44% by weight of the total weight of the formulation; and an effective amount of at least one gel agent in an amount of 1.0 to 90% by weight of the total weight of the formulation; A pharmaceutical formulation comprising:

2. 10. The pharmaceutical formulation of claim 1, further comprising at least one carrier present as a further addition in an amount of 1 to 10% by weight relative to the total weight of the formulation.

3. 10. The pharmaceutical formulation of claim 1, further comprising 1 to 10% by weight of at least one additive selected from sweeteners, flavors, colorants, fragrances, preservatives, stabilizers, acids, bases, buffers, surfactants, diluents, or combinations thereof as a further addition based on the total weight of the formulation.

4. 10. The pharmaceutical formulation of claim 1, wherein the at least one peroxide source compound is urea peroxide.

5. The at least one antimicrobial compound may be selected from the group consisting of tetracycline, doxycycline, chlortetracycline, clomocycline, demeclocycline, lymecycline, meclocycline, methacycline, omadacycline, oxytetracycline, penimepicycline, rolitetracycline, sarecycline, minocycline, clindamycin, azithromycin, amoxicillin, clavulanic acid, metronidazole, ciprofloxacin, gemiflo 2. The pharmaceutical formulation of claim 1, wherein the active ingredient is selected from the group consisting of ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, metronidazole, cephalexin, clarithromycin, cefazolin, cefaclor, cefdinir, cefuroxime, cefadroxil, cefepime, ceftriaxone, or a combination of minocycline, metronidazole, and ciprofloxacin, salts thereof, prodrugs thereof, or combinations thereof.

6. 10. The pharmaceutical formulation of claim 1, wherein the at least one antimicrobial compound is tetracycline, a salt thereof, or a prodrug thereof in an amount of 10-40% by weight of the total weight of the formulation.

7. 10. The pharmaceutical formulation of claim 1, wherein the at least one antimicrobial compound is tetracycline, a salt thereof, or a prodrug thereof in an amount of 25-30% by weight of the total weight of the formulation.

8. 10. The pharmaceutical formulation of claim 1, wherein the formulation is formulated as a gel, paste, toothpaste, mouthwash, rinse, dental floss coating, chewing gum, oral care strip or film applied directly to or adhered to oral surfaces, lozenge, or combinations thereof, without any Schedule IV analgesic narcotics.

9. 9. The method of claim 1, wherein the topical dental pharmaceutical preparation is applied to the dental tissue. In the subject's oral cavity, bleeding; swelling; pain; Gum recession; recession of tooth-supporting bone; Loss of tooth-supporting bone mass; or a combination thereof A method for treating or preventing at least one of the following:

10. an effective amount of at least one antimicrobial compound in an amount of 5 to 90% by weight of the total weight of the topical dental pharmaceutical formulation; an effective amount of at least one peroxide source compound in an amount of 1.5 to 44% by weight of the total weight of the formulation; and an effective amount of at least one gel agent in an amount of 1.0 to 90% by weight of the total weight of the formulation; administering to a patient in need of such administration an effective amount of a topical dental pharmaceutical formulation comprising Equipped with wherein at least one symptom is minimized or eliminated compared to said patient without said administration of said topical dental pharmaceutical formulation, said symptom being: bleeding gums of said patient; swelling of the patient's gums; the patient experiences pain in the gums or teeth; said patient's gum recession; recession of said patient's tooth-supporting bone; loss of tooth-supporting bone mass in said patient; or a combination thereof.

1. A method of treating an oral anatomical structure selected from:

11. 11. The method of claim 10, further comprising applying anesthesia to the root of at least one of the patient's teeth before, during, after, or a combination thereof, the administration of the topical dental pharmaceutical preparation.

12. 11. The method of claim 10, further comprising topically administering to the patient an effective amount of at least one growth factor-enhanced matrix material comprising human growth factors and an osteoconductive matrix, wherein the topical administration of the growth factor-enhanced matrix material is accomplished before, during, after, or a combination thereof, of the administration of the topical dental pharmaceutical preparation.

13. 11. The method of claim 10, further comprising systemically administering to the patient an effective amount of at least one antimicrobial compound, wherein the systemic administration of at least one antimicrobial compound is accomplished before, during, after, or a combination thereof, of the administration of the topical dental pharmaceutical formulation.

14. 11. The method of claim 10, wherein the recession of the patient's gums, the recession of the patient's tooth-supporting bone, the loss of tooth-supporting bone mass in the patient, or a combination thereof is eliminated.

15. Administering an effective amount of the topical dental pharmaceutical formulation to a patient comprises: the amount of the formulation administered to the patient in a treatment session; the duration of time that the formulation is in contact with the oral anatomical structures of the patient having at least one symptom; the frequency with which the formulation is administered to the affected oral area of ​​the patient, or a combination thereof. The method of claim 10 , comprising at least one of:

16. 11. The method of claim 10, wherein administering an effective amount of the topical dental pharmaceutical formulation to the patient is accomplished without one or more of general anesthesia; local anesthesia; or an analgesic.

17. 11. The method of claim 10, further comprising at least one of: rinsing the patient's mouth with one or more rinses to remove excess or residual topical dental pharmaceutical preparation; preventing the patient from swallowing the topical dental pharmaceutical preparation; or both.

18. The method of claim 10, wherein administering an effective amount of the topical dental pharmaceutical preparation to a patient provides better wound healing to the patient who has undergone oral surgery compared to the patient without the administration of the topical dental pharmaceutical preparation.

19. The step of administering the topical dental pharmaceutical preparation to a patient in need of such administration comprises: Reduction or cessation of gum recession; Reduction or cessation of tooth-supporting bone recession; Reduction or cessation of tooth-supporting bone loss; Reduction or elimination of bleeding of said oral anatomical structures; Reduction or elimination of swelling of said oral anatomical structures; Reduction or elimination of pain sensation in said oral anatomical structures; Enhanced bone regeneration; Enhanced soft tissue repair; or a combination thereof Providing synergistic results, including The method of claim 10.

20. 11. The method of claim 10, wherein oral prophylaxis is provided to a patient by administering to the patient an effective amount of the topical dental pharmaceutical preparation.

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