Topical Medicines Research Articles

Effect of coded Unani formulation Unim-401 and Soranil with NB-UV-B therapy in a case of chronic palmo-plantar plaque psoriasis- A Case Study.

Da’ al-Sadaf (Plaque psoriasis) is the most common form of the psoriasis in which raised, red patches covered with a silvery white buildup of dead skin cells. These patches or plaques most often show up on the scalp, knees, elbows and lower back. Sometimes it is itchy and painful and, may cracked and bleed. Unani oral and topical medicines along with Narrow Band Ultra-Violet (NB-UV-B) therapy is used here for treatment. Unani coded formulation UNIM-401 containing Barg Shahtra (Fumaria parviflora Linn.), Chiraita Talkh (Swertia chirata Buch.), Babchi (Psoralea corylifolia Linn.) and Haleela Siyah (Terminalia chebula Retz.) in the ratio of 5:5:5:2, in a dose of 2 capsules (500 mg each) orally with lukewarm water twice a day in empty stomach for a period of three months are given and Soranil ointment mixed with clarified butter in 1:1 ratio was applied on the affected part and exposed to the NB-UVB light for 10 minutes. Plaques of psoriasis getting shade off after one month of treatment and almost disappeared from the site of lesion after three months. The skin of patient almost become normal. It may be concluded that Unani drugs (oral & topical) along with NB-UVB therapy is beneficial for controlling and treating plaque psoriasis.

Topical cannabis-based medicines - A novel adjuvant treatment for venous leg ulcers: An open-label trial.

Venous leg ulcers are highly prevalent lower limb integumentary wounds that remain challenging to heal despite the use of evidence-based compression therapies. A multitude of adjuvant treatments has been studied but none have demonstrated enough efficacy to gain adoption into treatment guidelines. Global attention on Cannabis-Based Therapies is increasing and has been driven by quantum scientific advancements in the understanding of the endocannabinoid signalling system. Topical Cannabis-Based Medicines represent a novel treatment paradigm for venous leg ulcers in terms of promoting wound closure. Fourteen complex patients with sixteen recalcitrant leg ulcers were treated with Topical Cannabis-Based Medicines in conjunction with compression bandaging, every second day, to both wound bed and peri-wound tissues. The cohort had a mean age of 75.8years and was medically complex as reflected by a mean M3 multimorbidity index score of 2.94 and a mean Palliative Performance Scale score of 67.1%. Complete wound closure, defined as being fully epithelialized, was achieved among 11 patients (79%) and 13 wounds (81%) within a median of 34days. All three remaining patients demonstrated progressive healing trends but were lost to follow-up. The treatments were well tolerated, and no significant adverse reactions were experienced. The rapid wound closure of previously non-healing venous leg ulcers among elderly and highly complex patients suggests that Topical Cannabis-Based Medicines may become effective adjuvants in conjunction with compression therapy. This may also indicate that they may have an even broader role within integumentary and wound management. Therefore, this treatment paradigm warrants being subjected to controlled trials.

Difficulties in therapy of aerobic vaginitis and ways to overcome them

Pathological discharge from the genital tract and other signs of discomfort of the external genitalia are a common cause of a visit to the gynecologist. The cause of these disorders in most cases is vulvovaginal infection, accompanied (vaginitis) or not accompanied (vaginosis) by leukocyte reaction. Methods for treating vulvovaginal infection are predominantly local therapy or systemic agents with highly selective antimicrobial activity. Since a significant part of the vaginitis is of mixed polymicrobial origin, treatment should be complex, which determines the possibility of prescribing topical medicines containing several components of a wide spectrum of action. At the same time, the complexity of diagnosis and the time spent on it allow one to talk about the advisability of empirical therapy of vulvovaginitis, accompanied by severe clinical symptoms.

Topical Chinese patent medicine for knee osteoarthritis pain

Purpose: Topical non-steroidal anti-inflammatory drugs (NSAIDs) are currently strongly recommended for individuals with osteoarthritis (OA), according to 2019 American College of Rheumatology Guideline. However, topical Chinese Patent Medicine (CPM), which has been widely used to improve clinical symptoms for OA in eastern countries is less defined. A comprehensive review of the literature is an important step for understanding its benefits for OA. We systematically reviewed the literature on the clinical efficacy of topical CPM in patients with knee OA to inform clinical practice.

Dense nanolipid fluid dispersions comprising ibuprofen: Single step extrusion process and drug properties

Dense nanolipid fluid (DNLF) dispersions are highly concentrated aqueous dispersions of lipid nanocarriers (LNCs) with more than 1015 lipid particles per cubic centimeter. Descriptions of dense nanolipid fluid dispersions in the scientific literature are rare, and they have not been used to encapsulate drugs. In this paper we describe the synthesis of DNLF dispersions comprising ibuprofen using a recently described twin-screw extrusion process. We report that such dispersions are stable, bind ibuprofen tightly and yet provide high transdermal drug permeation. Ibuprofen DNLF dispersions prepared according to the present study provide up to five times greater flux of the pharmacologically active S-ibuprofen isomer through human skin than a commercially available racemic ibuprofen emulsion product. We demonstrate scaling up the twin-screw extrusion method to pilot production for a stable, highly permeating ibuprofen DNLF composition based on excipients approved by the US FDA for use in topical products as a key step towards development of a commercially viable, FDA approvable topical ibuprofen medicine to treat osteoarthritis, which has never before been accomplished.

TO ASSES THE EFFICACY OF MOMETASONE AND HYDROXYPROPYLMETHYLCELLULOSE NASAL SPRAY TO CONTROL SYMPTOMS OF ALLERGIC RHINITIS: A COMPARATIVE STUDY

Allergic rhinitis is very common disorder. It significantly effects patient's daily life. So many drugs are in use for the control of symptoms of allergic rhinitis.Steroid nasal spray was the mainstay of topical medicine for long.Hpmc powder nasal sprayis not so old medication used now a days.In our study we try to find out the effictiveness of mometasone and HPMC powder nasal spray to control the symptoms of allergic rhinitis.In each group we had 60 nos of patient receiving the medication as stated. Evaluation was done at 14th days and 28th days of starting the drugs. At day 14th The chisquare statistic was 1.8682. The p value was 0.602. The result was not significant as p more than o.5. there was same response for both drugs at 14th day of starting treatment.At day 28h The chi-square statistic was 14.8428.The p value was 0.005039.The result was significant as p less than o.5.there was same response for both drugs at 28th day of starting treatment. There was more relief of major symptoms and complete relief of symptoms with HPMC powder nasal spray at 28th day of treatment.The value of z (two proportion test ) is -3.7158 .The value of p is 0.0001.There was minimal side effects for both drugs.only 7 nos of patients said that three times daily dosage of HPMC is not convenient

Human Nails Permeation of an Antifungal Candidate Hydroalcoholic Extract from the Plant Sapindus saponaria L. Rich in Saponins.

We evaluated a hydroalcoholic extract of Sapindus saponaria L. pericarps (ETHOSS), as a candidate to a topical antifungal medicine for onychomycosis. ETHOSS was produced by extracting the crushed fruits in ethanol. The saponin contents were identified and characterized by electrospray ionization mass spectrometry. We measured the in vitro antifungal activity against three dermatophyte fungi, isolated from onychomycosis: Trichophyton rubrum, T. mentagrophytes, and T. interdigitale, using broth microdilution tests. The minimum fungicide concentration of ETHOSS ranged from 195.31 to 781.25 μg/mL. The cytotoxicity of the crude extract was tested on the HeLa cell line, and its ability to permeate into healthy human nails by photoacoustic spectroscopy and Fourier transformation infrared spectrometer (FTIR) spectroscopy by attenuated total reflection. Besides its strong antifungal activity, ETHOSS showed low cytotoxicity in human cells. It was able to permeate and reach the full thickness of the nail in one hour, without the aid of facilitating vehicles, and remained there for at least 24 h. These results suggest that ETHOSS has great potential for treating onychomycosis.

Dermatology and Randomized Control Trials.

Well-designed and rigorously conducted randomized controlled trial (RCT) can produce most valid and precise scientific evidence. Any intervention, be it systemic or topical medicine, dermatology procedure needs to be tested for its efficacy in improving particular disease condition and RCT should come into mind of investigator. The biggest strength of RCT lies in two self-explanatory factors; they are randomized and controlled. Randomization of study subjects eliminates selection and confounding bias and controlling of study condition improves the internal and external validity of findings. “Blinding” eliminates assessment bias. If one starts a comparative study without stating proper hypothesis, he/she would end up collecting lots of data which does not make sense. PICOT format helps in formulating research question. Writing a detailed protocol based on hypothesis describing in detail methodology, sample size calculation, randomization method, and blinding procedure up to statistical analysis plan is very important step in planning of RCT. Trials registered prospectively contribute to transparency of the trial and are considered to reduce the publication bias by reducing selective publication of positive outcomes. Adverse events can occur at any time during conduct of an RCT and should be reported and kept track of. Physical injury resulting from clinical trial participation is entitled to financial compensation. During preparation of final manuscript of study, the CONSORT guidelines must be followed to improve the quality of reporting of RCTs. Clinical trials provide evidence-based approach in medicine and a designed and well-implemented trial can alter clinical dermatology practice for a healthier tomorrow.

EVALUASI PERESEPAN OBAT PASIEN RAWAT JALAN PUSKESMAS SUNGAI TABUK 1 KALIMANTAN SELATAN TERHADAP FORMULAIRUM KABUPATEN

Drug formularies are a guide for health workers in choosing drugs rationally. One of the benefits of formularies is controlling quality and optimizing services for patients. The conformity of prescription drugs to formularies is important to improve the quality of service. The purpose of this study was to assess the conformity of prescription drugs at Sungai Tabuk 1 Primary Health Care against the Banjar District Formulary for the period 2019. This retrospective descriptive study was conducted in January to February 2020 at the outpatient of Sungai Tabuk 1 Primary Health, South Kalimantan. Prescribing drugs at the outpatient of the 16 therapy classes, there are 13 therapy classes 100% according to the Banjar Regency Formulary for the period 2019. Meanwhile, 3 classes of less than 100% conformity therapy include anti-infection, topical medicines for the skin, and vitamins and minerals. The mean percentage of prescription drugs at the outpatient of Sungai Tabuk 1 in accordance with the Banjar Regency Formulary was 99.15.

Kampō medicine and Muro disease (Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex): Postscript and Historical Footnote.

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-dementia Complex (ALS/PDC) is a disappearing neurodegenerative disease in three former high-incidence foci of the U.S. territory of Guam, Papua-Indonesia (New Guinea) and Kii Peninsula, Honshu Island, Japan (Muro disease). We report additional data that associate medicinal use of cycad seed to Muro disease in the southern Kozagawa focus of ALS/PDC. In the other two ALS/PDC-affected populations, cycad seed was used as a traditional topical medicine in New Guinea and Guam and, additionally, for food on Guam.

The assessment and management of thermal burn injuries in a UK ambulance service: a clinical audit.

Background:Although burn emergencies are infrequently encountered, the ambulance service is often the first point of contact for patients in these situations. It is therefore important that these potentially devastating injuries are managed in accordance with the evidence base. Appropriate assessment and management of these patients in the pre-hospital phase will have a significant impact upon their long-term outcomes, such as scarring cosmesis and functionality.Aim and objectives:This audit was conducted to determine if patients presenting to one UK ambulance service with thermal burn injuries were managed safely, effectively and in a timely manner. Areas highlighted for improvement will assist in directing future pre-hospital research and educational requirements. Epidemiological data will also be provided.Results:278 thermal burn incidents occurring from June 2017 to May 2018 (inclusive) were included in this audit. A larger proportion of burn patients were paediatrics who fell into the 0–10 age category, most burn patients were injured at a home address and only nine of the overall sample were major burns. Only 35% of patients received adequate cooling of their burns, an essential first aid intervention. The assessment of pain (87%) and provision of analgesia (75%) showed a higher compliance rate. However, only 54% had pain reassessed after analgesia. There was a near 100% compliance rate for patients being managed without hydrogel dressings and topical medicines.Conclusion:The results indicate several areas for improvement within the ambulance trust. Of importance is the application of basic first aid, such as cooling. It is important not only to improve education among staff but also to understand non-compliance. It should be acknowledged that assessment of pain and provision of analgesia demonstrated far higher compliance compared to current pre-hospital evidence. Several points for education and research have been identified.

The efficacy and safety of using the topical medicine with combined action in patients with opportunistic vaginal infections

Relevance.Infections of the lower genital tract are one of the most common reasons for women to visit a gynecologist. According to various authors, among all vulvovaginitis, the highest percentage of patients visiting a doctor is bacterial vaginosis (2050%), vulvovaginal candidiasis (1739%), trichomoniasis (10%) and other genital infections (10%). In the management of patients with infectious processes of the genitals, the choice of the method of therapy is of great importance, which allows not only to influence the microbes-associates, detected in high concentrations in the womans vagina during the initial episode of the disease, but also to prevent the development of relapses.
 Aim.To evaluate the clinical and laboratory efficacy, adherence and long-term results of benzydamine use in patients with vulvovaginal candidiasis, aerobic vaginitis and bacterial vaginosis
 Materials and methods.The study included 31 women aged 18 to 49 years, who complained of abundant discharge from the genital tract, itching, burning, dyspareunia. A comprehensive clinical and laboratory examination was carried out, including the collection of anamnestic data, general and special gynecological examination, microscopy of vaginal smears, KOH test, determination of the pH of the vaginal environment, assessment of vaginal microbiocenosis by quantitative PCR in real time. All patients were prescribed benzydamine hydrochloride, which was used as monotherapy in the form of a vaginal solution according to the recommended treatment regimen specified in the instructions for medical use of the drug TantumRosa 1 (irrigation 2 times a day for 10 days).
 Results.In 1219 days after beginning treatment, 25 (80.6%) of 31 patients with laboratory signs of vaginal microflora alterations showed restoration of the normal vaginal biocenosis laboratory parameters. Of them, 8 patients initially had dysbiosis, 12 patients yeast-like fungi, 4 patients aerobic vaginitis and 1 patient a combination of dysbiosis and fungi. Herewith, all patients also noted clinical signs of improvement. In 1219 days after beginning treatment, 6 (1.4%) of 31 patients with laboratory signs of vaginal biocenosis alterations had unsatisfactory laboratory parameters; that is vaginal biocenosis alterations (a decrease in Lactobacillus spp. percentage). At the same time, there were no clinical signs of pronounced inflammation such as pathological discharge, hyperemia, vaginal swelling.
 Conclusion.Benzydamine hydrochloride can be widely used in gynecological practice due to its combined effects on inflammation of the vagina, good clinical and microbiological results. It is important to note that additional therapy with drugs which contain lactobacilli is required only in 19.4% of cases. The clinical and laboratory effectiveness of benzydamine hydrochloride (TantumRosa) was 96.8%, since the relapse rate after 3060 days of the study did not exceed 3.2%.

Topical Administration of Cannabidiol: Influence of Vehicle-Related Aspects on Skin Permeation Process.

Cannabidiol (CBD) is a non-psychoactive cannabinoid isolated from Cannabis sativa which, given its claimed beneficial properties and therapeutic potential, has lately aroused considerable attention from the scientific community. Starting from the little literature evidence, the main purpose of this study was to investigate the topical administration of CBD, with particular focus on the influence of vehicle-related aspects on the skin permeation process. This could provide useful information for the design of suitable drug delivery systems which could be used in developing topical medicines and cosmetics. In vitro human skin permeation studies were conducted using modified Franz diffusion cells to compare the performance of four solutions and two semisolid formulations. The Hildebrand solubility parameter was used to better understand the thermodynamic aspects implied in the partitioning process of the cannabinoid compound into the skin. It was interestingly found that a hydrophilic gel, mostly consisting of propylene glycol (79%, w/w), can be an optimal choice for the topical administration of CBD. Moreover, the feasibility of the preparation of CBD-loaded (trans)dermal patches, made with new printing technology, was also demonstrated.

Analgesic effects of Mathan Thylam- A pharmacognostic review

Mathan Thylam is a medicated oil which is widely used as a topical medicine. In native of Siddha system, this oil is prescribed to heal all types of ulcers and wounds. It is very effective in curing severe carbuncle ulcer of diabetes, diabetic foot ulcers. The oil has a wide variety of other therapeutic topical applications such as eczema, bedsores itches, weeping eczema, wounds, folliculitis, anal fistula, ear infections, per anal abscess, alopecia, non-healing of cut and burns wounds. The vital compositions of the mathan thylam are constituted with thurusu (copper sulphate), datura leaf and coconut oil. These active ingredients, present in mathan thylam acts to play a major role in healing ulcers. In this study, we aimed to prove the analgesic effect of mathan thylam. As a result of the presence of datura leaf, mathan thylam can be used as an unsurpassed analgesic than any other medicated oils. This oil is used to reduce pain as well as inflammation. The Phytochemical and GCMS analysis of a hydroalcoholic extract of the mathan thylam revealed the presence of coumarin, steroid, alkaloid, saponin, furan, quinine and triterpenoid. This comprehensive review includes information on botany, phytochemistry, pharmacology and ethnomedical uses of datura, which is the key ingredient in mathan thylam to be used as a topical analgesic.

A new treatment regime for facial angiofibromas in patients with tuberous sclerosis complex

British Journal of DermatologyVolume 183, Issue 4 p. e127-e127 Plain Language SummaryFree Access A new treatment regime for facial angiofibromas in patients with tuberous sclerosis complex First published: 04 October 2020 https://doi.org/10.1111/bjd.19438AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Tuberous sclerosis complex (TSC) is a genetic disorder affecting approximately one in every 6,000 to 10,000 people. The disease causes hamartomas, which are non-cancerous growths, to develop in many parts of the body. Facial growths that are composed of blood vessels and fibrous tissues, called facial angiofibromas (FAs), occur in up to 80% of TSC cases and cause significant distress to the patients. This study, from Taiwan, aimed to find out if a new treatment regime using two topical (applied to the skin) medicines, rapamycin and calcitriol, in combination would be an effective and safe treatment for TSC-related FAs. We enrolled 52 TSC patients with FAs who were assigned to apply either topical rapamycin (0.1%) or calcitriol (0.0003%) single-agent therapy (on its own) to one side of the face, and the two medicines as a combined treatment regime to the other side of the face, for 12 weeks. The patients were reassigned to use the ointment which worked best for another 12 weeks, and the treatment was then discontinued for 12 weeks. We evaluated the improvement of FAs by comparing the modified Facial Angiofibroma Severity Index (mFASI; score 0-10), which was calculated by the sum of erythema, meaning redness (0-3), papule (a raised area of skin tissue) size (0-3), papule elevation (0-3), and extent of lesions (0-1), at weeks 12 (used as the primary outcome), 24, and 36 from baseline (the start of the trial). We found that the mean reduction of mFASI at week 12 compared to baseline was -0.92 and -1.09 for rapamycin and rapamycin-calcitriol combination, respectively. Compared to rapamycin alone, extended use of the rapamycin/calcitriol combination regimen for 24 weeks showed more effectiveness in decreasing papule elevation and could maintain a longer improvement after stopping treatment. We concluded that topical rapamycin/calcitriol combination therapy is an effective and safe regimen for TSC-related FAs. Linked Article: Chen et al. Br J Dermatol 2020; 183:655–663. Volume183, Issue4October 2020Pages e127-e127 RelatedInformation

Nanophthalmos patient with a THR518MET mutation in MYRF, a case report

BackgroundNanophthalmos has a significant genetic background and disease-causing mutations have been recently been reported in the myelin regulatory factor (MYRF) gene. We report clinical features in a patient with nanophthalmos and a Thr518Met MYRF mutation.Case presentationA three-year-old male was discovered to have nanophthalmos after first presenting to the emergency department for a frontal headache, eye pain, emesis, and lethargy. Imaging studies (CT and MRI) were negative except for increased posterior fossa cerebrospinal fluid. Subsequent examinations revealed nanophthalmos (short axial eye lengths 18.1 mm OD and 18.3 mm OS), microcornea, and a large crystalline lens. Peripheral chorioretinal pigment abnormalities were also observed. He experienced episodes of marked ocular hypertension (53 mmHg OD and 60 mmHg) likely due to intermittent angle closure precipitated by nanophthalmos. The ocular hypertension was responsive to topical medicines. Genetic analysis of known nanophthalmos genes MFRP and TMEM98 were negative, while a novel mutation, Thr518Met was detected in MYRF. The Thr518Met mutation was absent from 362 matched normal controls and was extremely rare in a large population database, allele frequency of 0.000024. The Thr518Met mutation altered a highly conserved amino acid in the MYRF protein and three of four algorithms suggested that this mutation is likely pathogenic. Finally, molecular modeling showed that the Thr518Met mutation is damaging to MYRF structure. Together these data suggest that the Thr518Met mutation causes nanophthalmos.ConclusionsNanophthalmos may present at an early age with features of angle closure glaucoma and a Thr518Met mutation in MYRF was detected in a patient with nanophthalmos. Prevalence data, homology data, mutation analysis data, and protein modeling data suggest that this variant is pathogenic and may expand the phenotypic range of syndromic nanophthalmos caused by MYRF mutations to include central nervous system abnormalities (increased posterior fossa cerebrospinal fluid).

Anticancer activity of topical ointments with histone deacetylase inhibitor, trichostatin A

Trichostatin A (TSA), being a strong specific histone deacetylase (HDAC) inhibitor, may lead to the inhibition of growth, differentiation and/or apoptosis of cells in a number of tumors. Semisolid drug formulations for topical release of anticancer agents may be an alternative strategy or a supplement of the systemic therapy. To prepare semisolid formulations with TSA to be used directly on the skin and to assess the anticancer effect in vivo on a mouse model with L1 neoplastic tumors. Twenty-four formulations were prepared in the form of semisolid systems containing TSA as the active ingredient. Then, an in vitro study was performed concerning the release of the active substance from the prepared formulations. Four formulations were selected for in vivo studies: oil-in-water cream, hydrogel, w/o emulsion ointment on the absorptive hydrophobic medium, and o/w emulsion gel. The tumor size and mouse body weight were measured during the experiment. The tumors and healthy skin of the mice were assessed regarding the skin barrier function with the Corneometer and Tewameter probes. The semisolid formulation with TSA applied on the skin reduced the growth of neoplastic tumors as compared with the control group. This is especially pronounced in the case of w/o emulsion ointment and o/w emulsion gel. The Corneometer shows that neoplastic tumor growth and formulations on the skin have no effect on the skin condition in comparison with the mouse skin without tumor. The measurement performed with the Tewameter has revealed impaired skin barrier function of neoplastic tumors. Semisolid formulations with TSA fit well in the mainstream of research into topical medicines applied directly on neoplastic tumors, which may support and supplement current oncological treatment.

Voltage-dependent modulation of TRPA1 currents by diphenhydramine

Diphenhydramine (DPH) has been broadly used to treat allergy. When used as a topical medicine, DPH temporarily relieves itching and pain. Although transient receptor potential type A1 (TRPA1) channel is known to play roles in both acute and chronic itch and pain, whether DPH affects the activities of TRPA1 remains unclear. Using whole-cell patch clamp recordings, we demonstrated that DPH modulates the voltage-dependence of TRPA1. When co-applied with a TRPA1 agonist, DPH significantly enhanced the inward currents while suppressing the outward currents of TRPA1, converting the channel from outwardly rectifying to inwardly rectifying. This effect of DPH occurred no matter TRPA1 was activated by an electrophilic or non-electrophilic agonist and for both mouse and human TRPA1. The modulation of TRPA1 by DPH was maintained in the L906C mutant, which by itself also causes inward rectification of TRPA1, indicating that additional acting sites are present for the modulation of TRPA1 currents by DPH. Our recordings also revealed that DPH partially blocked capsaicin evoked TRPV1 currents. These data suggest that DPH may exert its therapeutic effects on itch and pain, through modulation of TRPA1 in a voltage-dependent fashion.

Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis

Tapinarof is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for atopic dermatitis (AD) and psoriasis treatment. A phase 2b, double-blind, vehicle-controlled study randomly assigned adolescents and adults with AD to receive tapinarof cream 0.5%, 1%, or vehicle, onceor twice daily, for 12weeks with a 4-week follow-up. Outcomes included Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), body surface area affected, pruritus numeric rating scale scores, patients' impressions of AD and pruritus symptom severity, and Patient-Oriented Eczema Measure (POEM) scores. Overall, 191 of 247 randomized patients completed the study. Week 12 IGA responses were higher in the tapinarof groups versus the vehicle group, reaching statistical significance with tapinarof 1% twice daily, ≥75%/90% improvement in EASI from baseline were significantly higher in the tapinarof groups (except 0.5% once daily and 0.5% twice daily), EASI scores were significantly improved in all tapinarof groups, and body surface area affected was significantly reduced in the tapinarof groups (except 0.5% twice daily). More patients reported AD and pruritus symptom severity as very/moderately improved in tapinarof groups, and POEM improvements were observed in all groups. Most adverse events were mild or moderate. Larger prospective studies are required to confirm the reported analyses. Tapinarof is a potential important advance in topical medicine development for AD.

Amelioration of muscular spasm-induced pain of Guangtongxiao recipe in a non-everted gut sac in vitro model

BackgroundThe modern study of the traditional Chinese medicine (TCM) compound recipes is a complex issue because of the large number of components in the recipes that would produce several metabolites after entering the body. The TCM compound recipes are known to have the advantage of synergistic treatment by multiple targets due to diverse components. Therefore, a research method that can reflect the overall effect of compounds with multi-components is essential. The pharmacological studies of the classic TCM compound recipes mainly use the sero-pharmacological method. It is a semi-in vivo study method, and the drug to be tested in the in vitro experiment is the drug-containing serum from the model animals (the drug to be tested is a mixed drug system containing the prototype drugs in animal bodies that have pharmacodynamic effects and the metabolites). Herein, a safe and effective external TCM recipe was used to develop another semi-in vivo experimental method to reflect the overall effects of TCM. AimTo observe the effects of in-vitro intestinal absorption liquid of aqueous extracts of the TCM compound recipe—Guangtongxiao foam aerosol (Guangtongxiao)—on the tension of isolated rectal rings of mouse and investigate the underlying mechanisms of antispasmodic and amelioration of muscular spasm-induced pain. MethodsIntestinal absorption liquid of the Guangtongxiao aqueous extract at the five time points (30, 45, 75, 105, and 120 min) was prepared using a non-everted gut sac method. The isolated rectal rings of mice were prepared by pre-contraction using potassium chloride (KCl) or acetylcholine chloride (ACh) to make steady contraction. The intestinal absorption liquid were added cumulatively to the sink with the constricted rectal rings. The effects of the five groups of the intestinal absorption liquid with different drug concentration were observed on the tension of the isolated rectal rings. Then the ex vivo perfusion of the mouse rectal ring was performed as same as Guangtongxiao intestinal absorption liquid experiments, and the effects of two major components of Guangtongxiao, paeoniflorin (Pae) and tetrahydropalmatine (THP), on the rectal ring pre-treated with high concentration of KCl and ACh to induce contraction were studied. ResultsThe relaxation rate of the five groups of the intestinal canals increased significantly with 3200 μL cumulative sample volume as compared to the blank group (P < 0.01). It suggested that the relaxation activity of the intestinal absorption liquid enhanced significantly with the prolongation of the interaction between isolated rectal rings and intestinal absorption liquid in a time-dependent manner. Also, significant differences were detected while comparing between the 120-min intestinal absorption liquid group and the blank group with respect to various cumulative sampling volumes (P < 0.01). In addition, the intestinal relaxation rate elevated gradually with the increase in sampling volume, indicating that the concentrations of active substances in the intestinal absorption liquid prepared by the non-everted gut sac model increased and the intestinal relaxation activity was enhanced with the prolongation of the absorption time in a dose-dependent manner. And Pae and THP in a concentration-dependent manner caused relaxation of the rectal ring, which is pretreated with high K+(KCl) and ACh to induce contraction. The EC50 of Pae and THP was 8.67 × 10−5 M (6.68 × 10−5-1.13 × 10−4) and 1.41 × 10−4 M (1.24 × 10−4-1.61 × 10−4) in the contraction model induced by KCl, and was 6.15 × 10−5 M (4.47 × 10−5-8.45 × 10−5), and 1.31 × 10−4 M(1.22 × 10−4-1.42 × 10−4) in the model induced by ACh, respectively. ConclusionThe intestinal absorption liquid of Guangtongxiao exerted a remarkable relaxation activity for the rectal rings, and relaxation of the smooth muscle tension might be one of the antispasmodic mechanisms of Guangtongxiao compound recipe. Also, adopting a semi-in-vivo experimental method to study the efficacy of topical external TCM recipe medicine is optimal.