Topical foam as a promising carrier system for active pharmaceutical ingredients: review of clinical studies.

Skin disorders are preferentially treated by topical administration of medicines or cosmetics because of the possibility of local action. However, a great concern is the delivery of topical actives with effective penetration through the stratum corneum to ensure the desired effect. Considering the search for a carrier system that allows the penetration/permeation of active pharmaceutical ingredients through this structure, searching for effective topical pharmaceutical forms is needed. Foams have been widely studied over the years due to their high capacity to favor the active to overcome the cutaneous barrier and because this form of presentation has ease of application and high acceptability by users. The objective of this review was to analyze the potential of foam as a topical pharmaceutical form for treating skin disorders, upon clinical cases reported in the literature. Foam presents technical advantages when compared to other conventional topical pharmaceutical forms due to its fast action, high tolerance, and safety, with reduction or total remission of adverse events. Regarding the patient, foam increased the rate of adherence to the treatment. Therefore, it is concluded that foam is an effective, secure, and stable topical presentation form for carrying active pharmaceutical ingredients and widely accepted by patients.

Involvement of the PKA pathway and inhibition of voltage gated Ca2+ channels in antihyperalgesic activity of Lippia grata/ß-cyclodextrin.

Neuropathic pain (NP) is a difficult condition to treat because of the modest efficacy of available drugs. New treatments are required. In the study we aimed to investigate the effects of the essential oil from Lippia grata alone or complexed in ß-cyclodextrin (LG or LG-ßCD) on persistent inflammatory and neuropathic pain in a mouse model. We also investigated Ca2+ currents in rat dorsal root ganglion (DRG) neurons. Male Swiss mice were treated with LG or LG/ß-CD (24 mg/kg, i.g.) and their effect was evaluated using an acute inflammatory pleurisy model and nociception triggered by intraplantar injection of an agonist of the TRPs channels. We also tested their effect in chronic pain models: injection of Freund's Complete Adjuvant and partial sciatic nerve ligation (PSNL). In the pleurisy model, LG reduced the number of leukocytes and the levels of TNF-α and IL-1ß. It also inhibited cinnamaldehyde and menthol-induced nociceptive behavior. The pain threshold in mechanical and thermal hyperalgesia was increased and paw edema was decreased in models of inflammatory and neuropathic pain. PSNL increased inflammatory protein contents and LG and LG-ßCD restored the protein contents of TNF-α, NF-κB, and PKA, but not IL-1ß and IL-10. LG inhibited voltage gated Ca2+ channels from DRG neurons. Our results suggested that LG or LG-ßCD produce anti-hyperalgesic effect in chronic pain models through reductions in TNF-α levels and PKA, and inhibited voltage-gated calcium channels and may be innovative therapeutic agents for the management of NP.

Central nervous system and analgesic profiles of Lippia genus

Abstract Many people use medicinal plants to relieve disorders related to the central nervous system, such as depression, epilepsy, anxiety and pain, even though the effectiveness of most of them has not yet been proven through scientific studies. Plants of the Lippia genus, Verbenaceae, are widely used in ethnobotany as a food, for seasoning and in antiseptic remedies. They are also marketed and used for the treatment of different types of pain, including stomach ache, abdominal pain and headache, as well as being used as sedatives, anxiolytics and anticonvulsants. Despite their widespread use, there are no reviews on the central nervous system profile of plants of this genus. Therefore, the databases Medline-PubMed, Embase, Scopus and Web of Science were searched using the terms Lippia and biologic activity. Thirty-five papers were found. Eleven species of Lippia showed central nervous system activity, with leaves and the aerial parts of plants being the most commonly used, especially in aqueous and ethanol extracts or volatile oil. The species are composed mainly of terpenoids and phenylpropanoids, including polyketides, flavonoids and in less quantity some alkaloids. Although several species of Lippia present analgesic activity, most studies have not explored the mechanisms responsible for this effect, however, there is some evidence that volatile oils and constituents of the extracts may be responsible for the relief of some CNS disorders, but the effects on pain modulation seem to be the most exploited so far.

Chemical composition and antibacterial activity of essential oil from leaves of Croton heliotropiifolius in different seasons of the year

ABSTRACT This paper reports the first study of the variation of the chemical composition and abundance of the essential oil of Croton heliotropiifolius, in four seasons, and the evaluation of its antibacterial activity. Essential oil obtained from leaves of C. heliotropiifolius were analyzed by GC/MS and evaluated against eight bacteria strains by broth microdilution method. The chemical constituents identified were the same in all samples, but with different proportions. The total percentages identified were 96.58% in summer, 92.08% in autumn, 98.44% in winter and 90.78% in spring. The majors constituents are β-caryophyllene, bicyclogermacrene, germacrene-D, limonene and 1,8-cineole. β-Caryophyllene was the major compound in all samples. The results of the antibacterial evaluations showed weak to moderate activity against the analyzed strains. In all analyzes was observed that essential oil sample collected in summer stands out from the others, displaying stronger activity against Gram-positive as Gram-negative bacteria.

Inclusion of terpenes in cyclodextrins: Preparation, characterization and pharmacological approaches.

Terpenes constitute the largest class of natural products and are important resources for the pharmaceutical, food and cosmetics industries. However, due to their low water solubility and poor bioavailability there has been a search for compounds that could improve their physicochemical properties. Cyclodextrins (natural and derived) have been proposed for this role and have been complexed with different types of terpenes. This complexation has been demonstrated by using analytical techniques for characterizing complexes such as DSC, NMR, XRD, FTIR, and TGA. The formation of inclusion complexes has been able to improve drug characteristics such as bioavailability, solubility and stability; and to enhance biological activity and efficacy. This review shows strong experimental evidence that cyclodextrins improve the pharmacological properties of terpenes, and therefore need to be recognized as being possible targets for clinical use.

ß-cyclodextrin complex containing Lippia grata leaf essential oil reduces orofacial nociception in mice - evidence of possible involvement of descending inhibitory pain modulation pathway.

The treatment of orofacial pain remains a major challenge for modern medicine. Thus, we prepared and physicochemically characterized a new ß-cyclodextrin complex containing Lippia grata leaf essential oil (ß-CD/EO) to investigate their possible antinociceptive activity in animal models of orofacial pain. The results of Differential scanning calorimeter (DSC) and Thermogravimetry/derivative thermogravimetry (TG/DTG) showed that the products prepared by Slurry complexation (SC) method were able to incorporate greater amounts of EO. In the X-ray diffractogram, it was shown that complex between EO and ß-CD was formed. Male Swiss mice were pre-treated with ß-CD/EO (6, 12 or 24 mg/kg, per os, gavage, p.o.), morphine (5 mg/kg, i.p.) or vehicle (distilled water, p.o.) 1 hr before treatment with formalin (20 µL, 2%), capsaicin (20 µL, 2.5 µg) or glutamate (40 µL, 25 µM) into the right upper lip. Our results demonstrated that p.o. treatment with ß-CD/EO was significantly (p < 0.05 or p < 0.001) capable of reducing the nociceptive face-rubbing behaviour in both phases of the formalin test. ß-CD/EO-treated mice were also significantly (p < 0.05 or p < 0.001) protected against nociception induced by capsaicin and glutamate. For the action in the central nervous system (CNS), ninety minutes after the treatment, the mice were perfused, the brains collected, crioprotected, cut in a criostate and submitted to an immunofluorescence protocol for Fos protein. The immunofluorescence protocol demonstrated that the ß-CD/EO significantly activated (p < 0.05; p < 0.01 or p < 0.001) the motor cortex, the Locus ceruleus, the nucleus raphe magnus and the periaqueductal gray of the CNS. These effects apparently did not alter, in tested doses, the motor coordination of mice in the rota-rod test. Our results proposed that ß-CD/EO might present an important draft of drug to the study of new compounds for the treatment of orofacial pain.

Chemical composition and antibacterial activity of essential oils from Myrcia alagoensis (Myrtaceae).

The chemical composition and antibacterial activity of essential oils obtained from fresh and dried leaves of Myrcia alagoensis O. Berg, collected in a secondary forest remnant in north-eastern Brazil, was compared. The essential oils were obtained by hydrodistillation from fresh and dried leaves, and analysed by GC/FID and GC/MS. The antimicrobial properties of the oils were investigated against five bacteria by determination of the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). The essential oils were rich in cyclic sesquiterpenes, such as germacrene B, with antibiotic action against Gram-positive and Gram-negative bacteria. The drying process after collection interfered with the chemical composition and antibacterial activity of the assessed samples.

[Annual cost of ischemic heart disease in Brazil. Public and private perspective]. / Custo anual do manejo da cardiopatia isquêmica crônica no Brasil. Perspectiva pública e privada.

OBJECTIVE: To estimate the annual cost of coronary artery disease (CAD) management in Public Health Care System (SUS) and HMOs values in Brazil. METHODS: Cohort study, including ambulatory patients with proven CAD. Clinic visits, exams, procedures, hospitalizations and medications were considered to estimate direct costs. Values of appointments and exams were obtained from the SUS and the Medical Procedure List (LPM 1999) reimbursement tables. Costs of cardiovascular events were obtained from admissions in public and private hospitals with similar diagnoses-related group classifications in 2002. The price of medications used was the lowest found in the market. RESULTS: The 147 patients (65 +/- 12 years old, 63% men, 69% hypertensive, 35% diabetic and 59% with previous AMI) had an average follow-up of 24 +/- 8 months. The average estimated annual cost per patient was R$ 2,733.00, for the public sector, and R$ 6,788.00, for private and fee-for-service plans. Expenses with medications (R$ 1,154.00) represented 80% and 55% of outpatient costs, and 41% and 17% of total expenses, in public and non-public sectors, respectively. The occurrence of cardiovascular event had a great impact (R$ 4,626.00 vs. R$ 1,312.00, in SUS, and R$ 13,453.00 vs. R$ 1,789.00, for HMOs, p<0.01) on the results. CONCLUSION: The average annual cost of CAD management was high, being the pharmacological treatment the main determinant of public costs. Such estimates may subsidize economical analyses in this area, and foster related healthcare policies.

Custo anual do manejo da cardiopatia isquêmica crônica no Brasil: perspectiva pública e privada / Annual cost of ischemic heart disease in Brazil: public and private perspective

OBJETIVO: Estimar o custo anual do manejo da doenca arterial coronária (DAC) em valores do SUS e convênios. MÉTODOS: Estudo de coorte, incluindo pacientes ambulatoriais com DAC comprovada. Considerou-se para estimar custos diretos: consultas, exames, procedimentos, internacões e medicamentos. Valores de consultas e exames foram obtidos da tabela SUS e da Lista de Procedimentos Médicos (LPM). Valores de eventos cardiovasculares foram obtidos de internacões em hospital público e privado com estas classificacões diagnósticas em 2002. O preco dos fármacos utilizado foi o de menor custo no mercado. RESULTADOS: Os 147 pacientes (65n12 anos, 63 por cento homens, 69 por cento hipertensos, 35 por cento diabéticos e 59 por cento com IAM prévio) tiveram acompanhamento médio de 24n8 meses. O custo anual médio estimado por paciente foi de R$ 2.733,00, pelo SUS, e R$ 6.788,00, para convênios. O gasto com medicamentos ($ 1.154,00) representou 80 por cento e 55 por cento dos custos ambulatoriais, e 41 por cento e 17 por cento dos gastos totais, pelo SUS e para convênios, respectivamente. A ocorrência de evento cardiovascular teve grande impacto (R$ 4.626,00 vs. R$ 1.312,00, pelo SUS, e R$ 13.453,00 vs. R$ 1.789,00, para convênios, p<0,01). CONCLUSAO: O custo médio anual do manejo da DAC foi elevado, sendo o tratamento farmacológico o principal determinante dos custos públicos. Essas estimativas podem subsidiar análises econômicas nesta área, sendo úteis para nortear políticas de saúde pública.