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Full-thickness skin grafts are a commonly used reconstructive method following Mohs micrographic surgery. The literature varies on the most appropriate methods of suturing and securing grafts as well as best practices to dress the graft postoperatively. Our objective was to review various approaches to management of full-thickness skin grafts, including suturing the graft, securing the graft, and topical emollient use on the graft postoperatively. It was found that absorbable sutures, plain gut, provide preferable outcomes with full-thickness skin grafts. The tie-over bolster is the most-used method for securing skin grafts after placement, although several other methods have demonstrated efficacy, including the polyurethane foam, sandwich, and quilting suture methods. While various topical emollients are used in the immediate postoperative period, plain white petrolatum is the least likely to form allergic contact dermatitis.

The aim of the study was to investigate the content of trace elements in deposited particulate matter and to estimate the health risk to Kraków inhabitants, caused by the exposure to heavy metals in particulate matter deposition. The qualitative and quantitative assessments of selected heavy metals in deposited particulate matter have been carried out in the city of Kraków (Małopolska, southern Poland, 5 measuring points) for seven months, between February and September 2017. A comparative study was conducted at the same time in Małopolska (5 measuring points). The deposited particulate matter was collected gravitationally, using measurement plates covered with aluminum foil and paraffin jelly. The largest deposition of particulate matter was found in May and June. The highest amount of deposited particulate matter and metals present in it was determined in Kraków. The Hazard Quotient (HQ) evaluation for non-carcinogenic effect showed low risk for each metal. In the case of lead in particulate matter, the carcinogenic risk value did not reach 10−6 hence this risk is acceptable. The total carcinogenic risk for all routes of exposure to cadmium was higher, indicating the risk of cancer in children and adults, with children more exposed. However, the carcinogenic risk for cadmium was also acceptable. The study showed that the problem of poor air quality concerns not only the city of Kraków, but also the entire Małopolska region. Elevated metal concentrations in particulate matter indicate the need for monitoring it in the air.

Petrolatum ointment, which is an oleaginous ointment, is generally produced through manufacturing processes such as melting, mixing, and cooling. In this type of semisolid formulation, the manufacturing conditions of each process are empirically known to affect the quality of the resultant preparation; however, in many cases, the details of the factors are unclear. To clearly investigate the influence of the pharmaceutical properties of petrolatum ointments, we manufactured several ointments while changing the conditions of the mixing and cooling process after melting white petrolatum. As a result, the temperature at the termination was determined to influence the pharmaceutical properties of the final product. To investigate these phenomena, each petrolatum ointment sample was examined via digital microscopy and laser Raman analysis, and the distribution of the liquid-solid parts of samples was investigated. The internal structure of the ointment sample manufactured at a mixing-stop temperature of 40 °C, the needle crystals and the spherical aggregates surrounding them appropriately coexisted, while the structure exhibited a state wherein the two were linked in a semisolid phase. Meanwhile, for the ointment sample manufactured under the lowest mixing-stop temperature of 25 °C, the liquid part and the spherical aggregates were clearly separated, indicating that the liquid part was easily separated from ointments. In addition, the distribution of the hydrocarbons among the samples was measured via GC-MS; no significant difference in chemical structure was observed. In conclusion, the internal structure of the petrolatum ointment was changed by the manufacturing conditions, and this affected the pharmaceutical properties.

Acute and minor skin wounds are common in daily life. However, in clinical practice, after initial management in the acute phase, the wounds are managed mainly through observation, and the patients are usually lost to follow-up. Considering a multicomponent hydrolipidic dressing (MAS063DP) long-known for its safe application in eczema and recently in laser-induced wounds, we aimed to evaluate its ability in functional recovery of impaired skin integrity during wound healing. Sixteen patients (N = 16) were enrolled and completed (n = 8 vs n = 8) this prospective, open-label, vehicle-controlled clinical trial with 12-week follow-up. Transepidermal water, skin viscoelasticity and bioimpedance analysis were measured initially, at the 1st, 4th, 8th, and 12th weeks. Improvements in these parameters were greater in the MAS063DP group (from 31.4 ± 9.0 to 16.4 ± 4.3 g/m2 h, P < .001; from 77 ± 16% to 88 ± 9%, P < .05; from 4182 ± 3823 to 2644 ± 1772 Ω) than in the white petrolatum group. No significant adverse events occurred, and all participants were more satisfied with the intervention. In this study, MAS063DP can restore skin integrity and reinstitute physiologic function as a feasible and safe intervention more markedly than management through observation during the healing process by providing protective hydrolipidic layer on the skin with simultaneous anti-inflammatory and antioxidant activities from its key ingredients such as glycyrrhetinic acid, Vitis vinifera, telmesteine, and vitamins C and E.

Background Petrolatum is often used to suppress water evaporation from the skin surface. However, its stickiness, shininess, and other factors make it inconvenient for continuous use. Objective To compare the effectiveness and usability between a newly developed petrolatum-based ointment (NOV® II Moisture Balm) and white petrolatum. Methods Twenty-nine subjects with atopic dermatitis or xeroderma with symptoms of dry skin applied NOV® II Moisture Balm on the right sides of the face and white petrolatum on the left side, respectively, for 8-12 weeks. The skin conditions (erythema, exudate/crusting, dryness, and itch) were scored, stratum corneum water content and transepidermal water loss (TEWL) were measured, and the free amino acid and thymic stromal lymphopoietin (TSLP) levels in the stratum corneum were analyzed before and end of the trial. Results Dryness, exudate/crusting, and TEWL decreased significantly on both the white petrolatum and the NOV® II Moisture Balm sides, while stratum corneum water content and the free amino acid levels in the stratum corneum increased significantly. On the NOV® II Moisture Balm side, erythema and the TSLP levels decreased significantly. In a questionnaire on usability, the subjects felt NOV® II Moisture Balm spread better and were less sticky and shiny than white petrolatum, and more subjects wanted to continue using NOV® II Moisture Balm. Conclusions NOV® II Moisture Balm was equivalent to white petrolatum in moisturizing and improving the physiologic functions of the skin, but had superior usability.

Actinic keratoses (AK) are precancerous lesions that develop on chronically sun-exposed skin. They frequently require prophylactic field treatment due to the risk of progression to squamous cell carcinoma. Topical treatment with 5-fluorouracil (5-FU) yields near complete AK resolution, yet leaves a patient with an exuberant erythematous treatment site, which may be embarrassing and/or uncomfortable. We report a case of a patient with diffuse facial AK who was treated with 5-FU twice daily for 2 weeks, resulting in fiery-red erythema and disrupted barrier indices. Application of pure ultra white petroleum jelly, an emollient preferred by dermatologists for post-operative wound healing, resulted in drastic decreased erythema and recovery time of post-treatment transepidermal water loss and hydration, compared to the contralateral, non-petrolatum-treated side. Additionally, petrolatum use did not disrupt the AK resolution endpoint. We suggest that petroleum jelly be used for the repair of 5-FU-induced barrier disruption and erythema to promote greater patient adherence.

Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo. Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography. Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro. Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

The physical stability of a prototypical pharmaceutical topical ointment, consisting primarily of an emulsion of propylene glycol droplets dispersed in a continuous white petrolatum medium, was studied with regard to droplet size growth and phase separation when the ointment undergoes heating or fluid shear. To investigate the effects of shear, the ointment at 32 °C was sheared using a transparent, narrow-gap, temperature-controlled Taylor-Couette flow apparatus operated under laminar flow conditions which provided approximately uniform shear rates. Optical methods based on microscopy were used to obtain in-situ, time-dependent propylene glycol droplet size distributions, while a wide-field lens and camera were simultaneously used to detect gross phase separation as the ointment was sheared. Microscopy was also used to observe and quantify ointment stability via analysis of droplet size evolution in the absence of fluid shear for a range of elevated temperatures. For a quiescent ointment, it was observed that the dispersed propylene glycol droplets do not exhibit any appreciable growth over a period of one month and temperatures as high as 45 °C. In contrast, fluid shear imposed at 32 °C was observed to cause rapid growth of dispersed phase droplets and the onset of large phase separated regions on time scales ranging between a few minutes to approximately half an hour for fluid strain rates ranging between 5.5 and 50 s−1, respectively. The experimental results from the lab-scale Couette flow apparatus were used to evaluate the risk of phase separation during commercial-scale manufacturing.

Background/Aims: An important pillar of AD management involves moisturizer application following bathing to restore epidermal barrier function (EBF). In this study, we aim to bring additional evidence to the “soak-and-smear” regimen, comparing EBF recovery by various moisturizers following bathing in AD and healthy subjects. Methods: Volar forearms of 10 AD patients and 10 healthy controls were immersed in water for 10 minutes to simulate bathing. Immediately after bathing, ceramide-containing emollient (CER), a humectant (10% glycerin, GLY), an occlusant (white petrolatum, PETR), and aloe vera 5% extract (ALOE) were applied to separate test sites on the forearm. One test site did not receive any moisturizer and served as control. EBF parameters (hydration, TEWL, and pH) were recorded at baseline, and 15, 30, and 60-minutes post-bathing.Results: AD and controls shared similar trends. ALOE had the most significant pH decrease while GLY had the highest pH increase. Hydration significantly increased in all moisturizers compared to control. GLY led to the highest increase, peaking at 15-minutes for both AD and healthy subjects. AD subjects had higher hydration following CER than healthy subjects throughout the entire study. All four moisturizers increased TEWL compared to control, though PETR had the lowest initial TEWL increase. Conclusion: All moisturizers has an immediate effect on improving SC hydration. Their initial effects on TEWL increase recovers toward control levels by 60-minutes. Future studies are needed to examine the effect of repeated moisturizer post-bathing over longer study periods.

The purpose of the present two phase 1 studies was to assess the safety, tolerability and pharmacokinetics for topical application of a novel Janus kinase (JAK) inhibitor, JTE-052, in Japanese healthy adult male volunteers and Japanese adult patients with atopic dermatitis (AD). Additionally, exploratory investigation was performed on the efficacy for disease severity and pruritus score in AD patients. In the QBX1-1 study, the cutaneous safety of JTE-052 ointment by a patch test and a photo patch test was assessed in an intra-individual comparative study using placebo ointment, white petrolatum and non-application as comparators. The study demonstrated that JTE-052 ointment would be associated with a low potential for phototoxicity but had no potential for skin irritation or photoallergy. In the QBX1-2 study, it was revealed that the systemic exposure to JTE-052 in both healthy volunteers with normal skin and AD patients with inflamed skin was low in application of not only 1% but also 3% JTE-052 ointment. JTE-052 ointments of 1% and 3% were generally safe and well tolerated in both populations. In a repeated twice-daily application for 7 days, the efficacy of JTE-052 ointment to AD patients was observed with both 1% and 3% ointments in the exploratory investigations evaluated by Eczema Area and Severity Index, Investigator's Global Assessment and Numeric Rating Scale assessments. The mean scores for each assessment declined from the baseline throughout the study. These results suggest that the treatment of JTE-052 ointment is generally safe and effective in AD patients, although further large confirmatory studies are needed.

Background: Topical agents used in combination with phototherapy or photochemotherapy may have both blocking or enhancing effects in ultraviolet rays. Objective: In this in vivo study, the effects of topical petrolatum, basis cream, glycerine, and olive oil on the transmission of ultraviolet A radiation were investigated. Methods: A test was performed to determine the minimal phototoxic dose on 29 volunteers with only psoralen plus ultraviolet A (PUVA) and then the same test was repeated with white petrolatum, basis cream, glycerine, olive oil, and sunscreen (0.3cc/25cm2). The effects of each agent on the minimal phototoxic dose were determined after 72 h. Results: When compared to pure PUVA, there was a statistically significant increase in the mean minimal phototoxic dose values by the application of white petrolatum (P = 0.011), but there was no significant increase or decrease in the mean minimal phototoxic dose values after the application of basis cream (P = 0.326), glycerine (P = 0.611) or olive oil (P = 0.799). Study limitations: Low number of patients Conclusion: The application of white petrolatum, which has a blocking effect, and also of basis cream immediately before PUVA therapy should not be recommended. Although we specify that glycerine and maybe olive oil can be used before photochemotherapy, there is a need for further research in larger series.

Background Aesthetically pleasing results and fast, uneventful recovery are highly desirable after rejuvenating ablative laser procedures. Wound dressings following ablative laser procedures should ideally improve and optimize the wound healing environment. Objective The purpose of this comparative split face, single blinded, prospective observational study was to assess the efficacy and acceptability of two primary wound dressings immediately after a full face fractional CO2 laser resurfacing procedure. Methods The assessments of an innovative film-forming dressing called Stratacel (SC) vs spring thermal water + Vaseline (V+), were conducted after a standardized, single pass, full-face ablative fractional CO2 laser skin resurfacing procedure. Clinical parameters such as haemoglobin – HB; surface temperature – ST; micro-textural modifications – MT; superficial melanin – M; intra-follicular porphyrines – P, were assessed at different phases of the healing process using standardized, non-invasive technologies. Results Five female volunteers were enrolled in this in-patient, controlled pilot study. Most of the clinical parameters considered, including 3D surface texture analysis, revealed a better performance of SC vs. V+ during the early, more delicate phases of the healing process. Conclusions This preliminary study, even if performed on a small number of volunteers, confirmed a definite advantage of the tested semi-permeable film-forming formula (SC) over a more conventional post-operative skin care regime (V+). Clinical results could be explained by a better uniformity of distribution of SC over the micro-irregularities induced by ablative fractional CO2 laser resurfacing. Its thin, semi-permeable film might, in fact act as an efficient, perfectly bio-compatible, full contact, temporary skin barrier, able to protect extremely delicate healing surfaces from potential environmental irritations. This article is protected by copyright. All rights reserved.

It is essential as well as challenging to develop a reliable in vitro release testing method for determining whether differences in release profiles exist between qualitatively and quantitatively equivalent ophthalmic ointment formulations. There is a lack of regulatory guidance on in vitro release testing methods for ophthalmic formulations. Three different in vitro release testing methods: 1) USP apparatus 4 with semisolid adapters; 2) USP apparatus 2 with enhancer cells; and 3) Franz diffusion cells were investigated. Qualitatively and quantitatively equivalent ointments were prepared via hot melting and simple mixing methods using four different sources of excipients (i.e. white petrolatum). The ointment formulations were characterized for content uniformity, particle size, and rheological parameters. All the formulations showed adequate content uniformity and similar particle size. The ointments prepared via the hot melting processes showed higher rheological parameters, as did the ointments prepared using ‘white’ petrolatum that exhibited a yellowish color. The three in vitro release testing methods were compared and evaluated for reproducibility, discriminatory capability, and correlation with the rheological parameters. Compared with the compendial methods, the non-compendial method (Franz diffusion cells) showed poorer reproducibility. All three methods possessed the ability to discriminate between the ophthalmic ointments with manufacturing differences. However, the USP apparatus 4 method displayed the largest margin of discrimination between the release profiles of the different ophthalmic ointments. In addition, the in vitro release rate obtained using the USP apparatus 4 method showed the strongest logarithmic linear correlation with the rheological parameters (Power law consistency index (K value) and crossover modulus) compared to the other two methods.

Steroid ointments are frequently mixed with moisturizer. It was reported that steroid ointments mixed with moisturizer increase permeability. There are only few studies done on the permeability of the moisturizer. We researched moisturizing effect of heparinoid ointment (Hirudoid Soft ointment) diluted with white petrolatum (Propeto) on the dry skin models by measuring water content of stratum. Two to four fold dilution of Hirudoid to white petrolatum resulted in a significant decrease in the moisturizing effect of the active ingredient. There was no significant difference in moisturizing effect between four times diluted mixture and white petrolatum alone. This leads to the conclusion that steroid ointment mixture with moisturizer is frequently used, but we should take more caution regarding the decrease of moisturizing effect.

A moisturizing cream mixed with a steroid ointment is frequently prescribed to patients suffering from atopic dermatitis. However, there is a concern that the mixing operation causes destabilization. The present study was performed to investigate the stability of such preparations closely using magnetic resonance imaging (MRI). As sample preparations, five commercial moisturizing creams that are popular in Japan were mixed with an ointment base, a white petrolatum, at a volume ratio of 1 : 1. The mixed preparations were stored at 60°C to accelerate the destabilization processes. Subsequently, the phase separations induced by the storage test were monitored using MRI. Using advanced MR technologies including spin-spin relaxation time (T2) mapping and MR spectroscopy, we successfully characterized the phase-separation behavior of the test samples. For most samples, phase separations developed by the bleeding of liquid oil components. From a sample consisting of an oil-in-water-type cream, Urepearl Cream 10%, a distinct phase-separation mode was observed, which was initiated by the aqueous component separating from the bottom part of the sample. The resultant phase separation was the most distinct among the test samples. To investigate the phase separation quantitatively and objectively, we conducted a histogram analysis on the acquired T2 maps. The water-in-oil type creams were found to be much more stable after mixing with ointment base than those of oil-in-water type creams. This finding strongly supported the validity of the mixing operation traditionally conducted in pharmacies.

In this symposium, we present a novel breathable protective ointment (BPO) formulation developed at the University of Shizuoka for the prevention of moisture-associated skin damage (MASD) intended for use in healthcare settings. MASD occurs when moisture is in constant contact with the skin for prolonged periods of time, causing degradation of the skin barrier. Exposure to physical or chemical stimuli in addition to moisture may lead to different types of moisture-associated dermatitis such as incontinence-associated or periwound dermatitis. Another type of moisture-associated dermatitis, diaper dermatitis, is treated with protective ointments such as white petrolatum and zinc ointment. These ointments protect the skin from irritants but also block insensible dermal perspiration, which promotes further skin maceration. Therefore, we have developed a BPO formulation from white petrolatum and calcium carbonate, which serve as a protectant and pore-forming agent, respectively. In vitro water-proof tests confirmed the skin-protective properties of the BPO, and moisture-permeation tests indicated its breathability. Moreover, the BPO protected the skin from irritants without the loss of skin hydration in rats. Our next step involves the trial of BPO in infants with diaper dermatitis. In the future, this BPO could be used as an ointment base for active pharmaceutical ingredients used to prevent MASD.

When selecting external medicines for the treatment of skin diseases, it is thought to be very important to consider differences in characteristics of their bases, because the bases may influence the clinical efficacy of the medicines. In this study, we investigated whether the differences in characteristics of three kinds of bases, white petrolatum, macrogol ointment, and aqueous gel affect wound healing. In vitro moisture permeability tests demonstrated that these bases have different characteristics in coatability and water retentivity, with the rank order of the intensity of coatability as white petrolatum>macrogol ointment>aqueous gel, and that of water retentivity as macrogol ointment>white petrolatum>aqueous gel. Similar rank order of these bases was observed for transepidermal water loss and stratum corneum water content in the dry skin on the abdomen of guinea pigs induced by topical application of acetone/ether mixture, followed by water. In addition, we found that treatment with macrogol ointment, but not white petrolatum or aqueous gel, significantly accelerated wound healing in rat skin, and that the contents of basic fibroblast growth factor and epidermal growth factor in the skin treated with macrogol ointment were significantly higher compared with non-treated skin. In conclusion, these results imply an important role of the bases of external medicines in the treatment of skin diseases.

Objective: To investigate the effect of a novel topical wound-healing agent, low-concentration povidone-iodine ointment (LPIO) with a hydrophobic white petrolatum-rich base on skin-wound models in rats and rabbits. Method: The therapeutic efficacy of topically applied LPIO was compared to that of standard-concentration povidone-iodine ointment (SPIO) and non-treatment control, using a full-thickness skin-wound model in 24 hairless rats and a full-thickness skin-defect model in rabbit earlobes. The animals were kept under standardised conditions at the Central Research Laboratory of Maruishi Pharmaceutical Co. Ltd. (Osaka, Japan). Therapeutic efficacy was evaluated based on macroscopic wound-size reduction, as well as histopathological and immuno-histochemical examinations. Results: LPIO enhanced wound healing in rat full-thickness skin ulcers, reducing wound size and inflammation, when compared with that in SPIO and non-treatment control. LPIO also markedly improved wound healing in rabbit earlobe ulcers by significantly improving re-epithelialisation, compared with that in SPIO. Conclusion: The results of this study suggest that LPIO is a useful topical therapy for ulcerative lesions.

Oleaginous white petrolatum ointment (WP ointment) is one of the most commonly used dosage forms in the preparation of topical products. In general, WP ointments containing medium chain fatty acid triglycerides (MCT) are manufactured through a process of melting, mixing, agitating, and cooling. To investigate the pharmaceutical properties of WP ointments in greater detail, we examined manufacturing factors which could potentially influence the pharmaceutical properties of the finished product. WP ointment samples containing 10% MCT were stirred with a homogenizer and a paddle mixer at 65°C, then the homogenizer was stopped. Next, the paddle-mixer was stopped at several planned temperature points at which different samples were taken. Each sample was then cooled under the following planned conditions: rapid-cooling [-50°C/h] and slow-cooling [-7.5°C/h]. The pharmaceutical properties of each WP ointment sample, along with the appearance (Optical/digital microscope), hardness (Rheometer), and bleeding ability (100 Mesh wire-net cone) were measured. Then, release profiles were performed with a WP ointment using the model active ingredient Vitamin D. As a result, high hardness, low bleeding ability and low release profile were observed in the WP ointment samples that were manufactured under the condition of stopping the paddle-mixer at 40°C. However, the influence of cooling speed was observed to affect only hardness. Through optical microscopic observation, it was found that the appearance of WP ointment samples differed depending on the conditions under which they were manufactured. In this study, it was clear that the pharmaceutical properties of WP ointment samples were particularly influenced by the paddle-mixer stopping temperature.

Most steroidal ointments contain propylene glycol (PG) and surfactants, which improve the solubility of corticosteroids in white petrolatum. Surfactants aid the uniform dispersal of PG within white petrolatum. Since the surfactants used in generic ointments are usually different from those used in brand name ointments, we investigated the effects of surfactants on the rheological properties of three brand name ointments and six equivalent generic ointments. We detected marked differences in hardness, adhesiveness, and spreadability among the ointments. Further examinations of model ointments consisting of white petrolatum, PG, and surfactants revealed that the abovementioned properties, especially hardness and adhesiveness, were markedly affected by the surfactants. Since steroidal ointments are often admixed with moisturizing creams prior to use, we investigated the mixing compatibility of the ointments with heparinoid cream and how this was affected by their surfactants. We found that the ointments containing glyceryl monostearate demonstrated good mixing compatibility, whereas those containing non-ionic surfactants with polyoxyethylene chains exhibited phase separation. These results were also consistent with the findings for the model ointments, which indicates that the mixing compatibility of steroidal ointments with heparinoid cream is determined by the emulsifying capacity of the surfactants in their oily bases., Graphical abstract fx1

Semisolid dosage forms are recommended for the dermal care of babies and children. If we look at the ingredients of these preparations, there are still many cases in which there are substances (occlusive agents, preservatives) that no longer meet certain requirements of the modern age, so it is timely to replace them with other substances. The aim of this work was to formulate a science-based formulation with new components that keep or improve its moisturizing properties, rheological parameters, and microbiological stability. Occlusive oils, like white petrolatum and liquid paraffin and the preservative parabens are traditional ingredients in oil in water creams, were replaced with white beeswax, sunflower oil, and phenoxyethanol, respectively. Cocoa butter, urea, and glycerol were added to improve long-lasting hydration and support the barrier function of the reformulated creams. The rheological properties of the formulations were determined. The effects of the preparations on skin hydration and on the barrier function of the skin were tested. Furthermore, microbiological stability was investigated. The result of the reformulation was an o/w cream that provided a good longer-lasting hydration effect, supported the barrier function of the baby skin without occlusion, and had adequate consistency, easy spreading, a pleasant skin feeling, proper pH, and good microbiological stability.

Excipients from different sources may lead to significant differences in the performance of drug products, posing challenges in product quality control. A previous report showed that the drug release rates from ophthalmic ointments were affected by source variation of white petrolatum. To understand the physicochemical properties including the microstructure of white petrolatum and the impact of this on the performance of finished products, the following were investigated: rheological properties, thermal analysis (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), as well as structural characteristics (polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS)). The rheological parameters may be indicative of the drug release rate of the finished ophthalmic ointments when using a process involving hot-melting with immediate cooling. The white petrolatum from the four different sources also showed different thermal behavior. According to SAXS and WAXS, all of the petrolatum showed semi-crystalline behavior with different extents of crystallinity (from 9.5% to 16.9%). The crystalline domains of the petrolatum are ordered in an orthorhombic structure forming lamellar sheets with a periodicity from 9.1 nm to 9.9 nm. An in-depth understanding of the semi-crystalline structure was obtained and it provided valuable information for formulation optimization and characterization of petrolatum-based products.

Objective : To compare the effect of natural oils and white petrolatum on skin barrier function in patients with xerosis. Design, Setting, and Participants : Randomized, open label, comparison pilot study (NCT03093597). Interventions : Participants were randomized to apply 1 of 4 moisturizers to assigned treatment areas twice daily for 2 weeks. Clinical dry skin score, stratum corneum hydration, and transepidermal water loss (TEWL) were assessed at baseline, 1 week, and 2 weeks. Results : Thirty-two participants completed the study. Neither TEWL nor hydration were statistically different among the moisturizers at each visit. All four moisturizers led to significant initial increase in TEWL at week 1 (p < 0.05) with an associated increase in hydration for coconut oil, jojoba oil, and white petrolatum. All four moisturizers led to significant increase in hydration by week 2 (p < 0.01). The preferred moisturizers were almond oil and coconut oil, which were most “liked” by 38% and 31% of the participants, respectively. The least preferred moisturizer was white petrolatum. Conclusions : Almond oil, jojoba oil, and coconut oil significantly increased hydration after 2 weeks, and are as effective as white petrolatum as daily moisturizers for xerosis. The participants preferred natural oils to white petrolatum, implying that these moisturizer options may improve patient compliance.

Background Angiokeratomas are benign vascular skin lesions characterised by proliferation of dilated blood vessels in the upper dermis. Some variants have been described that can affect different regions of the body including face and genitals. They may be isolated or clustered, and appear as small red-to-black papules, with a smooth epidermal surface. As the disease progresses, the lesions grow, reaching a diameter of 10 mm, and become dark red to black, with a verrucous surface. Depending on the characteristics of the lesions they can be treated with surgery or laser for aesthetic reasons. On the other hand, some investigators have also proved that topically applied rapamycin causes regression of facial angiokeratomas, giving better cosmetic results. Purpose To evaluate the efficacy and safety of the topical application of 0.4% rapamycin ointment in a facial angiokeratoma. Material and methods We report on a paediatric patient who presented with facial angiokeratomas. Rapamycin ointment was performed at a concentration of 0.4%, mixing with white petrolatum and petroleum jelly under safe conditions in a vertical laminar flow hood. Efficacy was measured in a paediatric judgement and through a monthly photographic examination. Safety was measured in terms of irritation and burning sensation. The patient was followed up for 1 year of treatment. Results The case of a male patient of 12 years of age (31 kg and 140 cm) is presented. After being approved the treatment in the Commission of pharmacy of our hospital, the patient started the treatment with one application every night. A photographic examination was performed, where an improvement was seen in the right malar zone, infraorbital, although the nasal area presented without changes. The patient had no irritation and burning sensation during treatment. The response of these vascular skin malformations to rapamycin, an mTOR inhibitor, suggests that activation of the PI3K/Akt/mTOR pathway in endothelial cells may play a role in the pathogenesis of angiokeratomas. Conclusion Topical rapamycin appears to be a promising and effective way of treating facial angiokeratomas. The major disadvantage is the cost of therapy, which is prohibitively expensive at the present time. References and/or Acknowledgements To my pharmacist colleagues No conflict of interest

Destruction of epidermal barrier function associated with atopic dermatitis or Darier's disease often causes severe secondary skin infections. Patients with skin barrier disorders often repeatedly acquire Kaposi varicelliform eruption, which is caused by herpes simplex virus, but the underlying mechanisms and effective preventive methods have yet to be found. Viral infection through an impaired epidermal barrier can be prevented by enhancing innate immunity and/or inhibiting viral entry. In this study, we established a three-dimensional skin barrier dysfunction model by silencing ATP2A2, which is mutated in some Darier's disease patients. We confirmed the loss of desmosomes and presence of histopathological clefts in the suprabasal layer. Herpes simplex virus 1 applied to the stratum corneum infected the deep epidermis. An innate immune reaction was assessed by evaluating the expression of IFNB1 and related genes. Pretreatment with polyinosinic-polycytidylic acid alone or plus the antimicrobial peptide, LL37 enhanced IFN-β production and suppressed viral replication. Furthermore, topical application of a white petrolatum ointment containing heparin, which binds viral glycoproteins related to virus entry, strongly inhibited viral replication, probably by inhibiting invasion. Our human barrier-dysfunctional model will have future application for identifying the mechanism of Kaposi varicelliform eruption onset, preventive methods, and therapies.

To develop a topical preparation of hirsutenone (HST), a natural immunomodulator, we formulated oleaginous ointments and creams and assessed their stability in terms of shelf-life. Ointments were prepared by mixing the molten lipid phase of white petrolatum and white beeswax with glycerin and propylene glycol, in which HST was dissolved with ascorbyl palmitate (AP), butylated hydroxyl toluene (BHT), or ethylenediaminetetraacetic acid (EDTA) as an antioxidant. Reference oil-in-water creams were formulated by conventional emulsification. The ointment and cream formulations were subjected to accelerated stability testing at 40 °C. At appropriate time points, test samples were dissolved in organic solvent, diluted with methanol, and filtered prior to high-performance liquid chromatography (HPLC). The degradation of HST in cream and ointment formulations followed first-order kinetics. The rate constants (day−1) of HST in cream and ointments were 1.71 × 10−2 and 0.67 × 10−2, respectively, revealing a 2.5-fold greater half-life in ointments than in creams. Although AP and BHT had no effect on chemical stabilization of ointments, EDTA enhanced the stability of HST at 40 °C. The shelf-lives of HST formulations were estimated by the Q10 method. Assuming a Q10 value of 2, the shelf-lives (days) of cream, ointment, and ointment with EDTA at 25 °C were 14.99, 38.23, and 44.19, respectively. At 4 °C, the shelf-life of HST in ointment with EDTA was extended to 220 days. Even though the stability of HST was somewhat increased by the ointment formulation and further improved by adding EDTA, alternative approaches are needed to increase stabilization.

A mixed preparation consisting of a water-in-oil emulsion-type moisturizing cream and a steroid ointment is frequently prescribed for the treatment of atopic dermatitis. We have investigated the compatibility of moisturizing creams and ointments because there are concerns regarding the physical stability of these mixed preparations. The key technology used in this study was magnetic resonance imaging (MRI). A commercial moisturizing cream and white petrolatum or clobetasone butyrate (CLB) ointment samples were mixed in a weight ratio of 1 : 1. A centrifugation test protocol (20000×g for 3 min) was implemented to accelerate the destabilization processes in the samples. After centrifugation, the mixed preparations separated into three distinct layers (upper, middle, and lower), while no phase separation was observed using moisturizing cream alone. The phase separation was monitored using chemical shift selective images of water and oil and quantitative T2 maps. In addition, MR and near-infrared spectroscopy were employed for component analysis of each phase-separated layer. Collectively, it was confirmed that the lower layer contained water, oils, and organic solvent, while the upper and middle layers were composed solely of oils. Furthermore, this study investigated the distribution of CLB in the phase-separated samples and showed that a heterogeneous distribution existed. From our results, it was confirmed that the mixed preparation became unstable because of the incompatibility of the moisturizing cream and ointment.

Arsenic is a known human carcinogen and skin manifestations are the earliest and most specific markers of chronic arsenic poisoning. A 43-year-old man from Luzon presented at the Section of Dermatology with a one-year history of hyperkeratotic papules and plaques on the palms and soles. Numerous round hypopigmented macules were scattered on the upper back. Initial 24-hour urine arsenic level was elevated at 288mcg/liter. The patient underwent successful chelation with Nacetylpenicillamine and the palmoplantar keratoses were treated with cryotherapy and topical 20% salicylic acid in white petrolatum. In cooperation with the Department of Health, a comprehensive health and environmental assessment was conducted in the affected communities. This case highlights the role of dermatologists in the diagnosis and management of this public health problem.

SummaryBackground and Aims Pruritus frequently reduces quality of life (QOL) in patients with senile xerosis. This study investigated the moisturizing and antipruritic effects of a topical emollient containing a diethylene glycol/dilinoleic acid copolymer (D/DC) in patients with pruritic senile xerosis. Methods This single-blind study involved 50 subjects, aged 50-75 years. Patients were randomized to self-applied treatment of the lower legs with 10% (n = 20) or 20% (n = 20) D/DC-containing cream, white petrolatum (n = 5), or no treatment (n = 5) thrice daily for four weeks. Clinical scores of skin dryness and scratch marks, skin conductance, and Skindex-16 were evaluated before and after treatment. The degree of pruritus was evaluated by visual analog scale (VAS) score once a week. Results Patients treated with 10% and 20% D/DC showed significant improvements in skin dryness and scratch mark scores, as well as increased skin conductance, compared with the untreated group, whereas white petrolatum treatment improved only skin dryness scores. Moreover, patients treated with 20% D/DC showed significant improvements in skin dryness scores and skin conductance compared with white petrolatum treatment. The VAS scores in the D/DC-treated and white petrolatum-treated groups were significantly lower than in the untreated group, being particularly lower after one week of treatment with 20% D/DC. Conclusion Topical application of an emollient containing D/DC is effective in improving skin dryness and pruritus in patients with senile xerosis.

The Goeckerman regimen is a unique combination therapy of UVB light and application of crude coal tar for the treatment of psoriasis, eczema, prurigo nodularis, and chronic pruritus. Coal tar is speculated to be an anti-inflammatory and a photosensitizer that can increase the effectiveness of phototherapy. In the Goeckerman regimen, patients first undergo UVB phototherapy per protocol. Then their body is covered in crude coal tar under plastic occlusion for 4–5 h. This is repeated daily, 5 days per week, for approximately 6 weeks. The efficacy of Goeckerman is superior to most other available therapies. For example, 100% of patients with severe psoriasis achieve 75% improvement or better from baseline by 12 weeks. Side effects include those of phototherapy (erythema, burning, and tanning), as well as irritation and folliculitis from tar products.

The aim of this study was to design porous matrix beads for floating drug delivery using enteric polymer, Eudragit® L and various amounts of waxes (0, 0.1, 0.5, 1, 2 and 3% w/w). In this study, wax containing cetyl alcohol and white petrolatum was utilized to produce pores using a wax removal technique. To prepare the beads, Eudragit® L, metronidazole and wax were dissolved in acetone and then extruded into dichloromethane. The effect of the amount of wax on the floating and drug release behavior of the Eudragit® L beads was determined. After the extruded product was immersed in dichloromethane, wax dissolved out from the formed beads, resulting in a porous structure. The prepared beads could float in simulated gastric fluid for more than 10 hours. Different amounts of wax had an effect on the drug release. We found that when the percentage of wax increased, the drug release was higher while the beads remained floating. The results suggest that Eudragit® L beads could be used as a carrier for an intragastric floating drug delivery system.

Objective: To investigate the effect of a novel topical wound-healing agent, low-concentration povidone-iodine ointment (LPIO) with a hydrophobic white petrolatum-rich base, on skin-wound models in rats and rabbits. Methods: We investigated the therapeutic efficacy of topically applied LPIO compared to that of standard-concentration povidone-iodine ointment (SPIO) and non-treatment control, using a full-thickness skin-wound model in hairless rats and a full-thickness skin-defect model in rabbit earlobes. Therapeutic efficacy was evaluated based on macroscopic wound-size reduction, as well as histopathological and immuno-histochemical examinations. Results: LPIO enhanced wound healing in rat full-thickness skin ulcers, reducing wound size and inflammation, when compared with that in SPIO and non-treatment control. LPIO also markedly improved wound healing in rabbit earlobe ulcers by significantly improving re-epithelialisation, compared with that in SPIO. Conclusions: The results of this study suggest that LPIO is a useful topical therapy for ulcerative lesions., 本文 / Central Research Laboratory, Maruishi Pharmaceutical Co., Ltd.; Department of Dermatology, Mie University Graduate School of Medicine, 24p

White petrolatum is frequently used as an oleaginous base, but has a drawback of poor usability. In this trial, white petrolatum was prepared at a lower melting point to improve its usability. Characteristic pharmaceutical values such as melting point, yield, and consistency were compared between a conventional product and ophthalmic white petrolatum. Usability was compared by administering a survey questionnaire and evaluating the comparable moisturizing effect by conductivity in humans. The melting point and yield value of the improved product were significantly lower compared with other white petrolatum products. In the survey, the improved product was rated excellent in five criteria. On a scale of 1 to 5, the average values for the five criteria for the improved product were 4.7, while the conventional product and ophthalmic white petrolatum were rated 3.0 and 3.5, respectively. No difference in moisturizing effect was observed among all petrolatums after application, from day 1 to day 14. In conclusion, the improved white petrolatum demonstrated better usability, and the moisturizing effect was equivalent to conventional product, suggesting that the use of this improved product may lead to improved adherence.

Background: Denture adhesive is widely used in elderly people who wear complete dentures. Chinese herbal medicine has long been used for the treatment of oral disease. The addition of herbal medicine to denture adhesive might be used to develop an adhesive which is effective for xerostomia patients. Purpose: The purpose of this study was to evaluate physical properties and cytototoxicity of herbal medicine components in denture adhesive. Methods: This study used a combination of 35wt% PVM-MA, 20wt% CMC, 40wt% white petrolatum and 5wt% liquid paraffin as base materials. Three kinds of herbal medicine components: Maimendong (Ophiopogon), Fuling (Hoelen) and Dongkuizi (Cluster mallow seed) were added to base materials of 1wt%, 5wt% and 10wt%. The initial viscosity was measured using a controlled-stress rheometer (AR-G2). The adhesive strength was quantified according to ISO-10873 recommended procedures. All data was analyzed independently by one-way Anova combined with a Turkey’s multiple comparison test at a 5% level of significance. Results: Significant differences were observed between materials in initial viscosity (p < 0.05). Specifically, samples containing 5wt% and 10wt% of Maimendong (Ophiopogon) showed higher values compared with the control samples. The larger the amounts of herbal medicine components, the greater the changes in the adhesive strength of denture adhesives over time. The denture adhesives containing herbal medicine components do not have a cytotoxic effect and are safe for use in actual clinical practice. Conclusion: The study showed that the addition of herbal medicine components does not affect physical properties (i.e. initial viscosity and adhesive strength) of denture adhesive and cytotoxicity in fibroblast cells.

Objective To describe the effects of long-term treatment with four different eye ointment bases (OBs) in cats. Animals studied Ten healthy cats. Procedures The study was performed in two periods. Four different OBs were tested. Hundred grams of OB contained the following: OB-A: 35.17 g liquid paraffin (lp), 64.83 g white petrolatum (wp); OB-B: 10.03 g lp, 84.95 g wp 5.02 g lanolin; OB-C: 18.34 g lp, 51.40 g wp, 25.00 mg KH2PO4, 57.00 mg K2HPO4, 18.90 g eucerinum anhydricum, 11.28 g water for injections; and OB-D: 70 g unguentum lanalcoli, 20 g lp, 10 g aqua conservans. One eye was treated, and the other served as a negative control. Cats received the OBs TID for 28 days. The two study periods were separated by a 4-month washout phase. Samples for conjunctival impression cytology, swabs for bacteriologic and mycologic examination, and cytobrush samples for FHV-1 and Chlamydophila felis PCR detection were obtained. Both eyes were examined daily. Severity of ocular symptoms was scored using a modified Draize eye irritation test. A total of five eyes were treated with OB-A, five with OB-B, four with OB-C, and five with OB-D. Results Treated eyes had significantly higher clinical scores. Eyes receiving OB-A had the highest overall clinical score. The results of bacteriologic and mycologic examination concur with the previously published data. All samples tested were negative for FHV-1 and Chlamydophila felis. There was no significant difference between treated and control eyes upon cytological examination. Conclusion The application of OBs resulted in clinical symptoms in treated eyes. The long-term use of ointments is not well tolerated in cats and may lead to ocular irritation.

White petrolatum is a mixture of solid and liquid hydrocarbons and its structure can be affected by shear stress. Thus, it might also induce changes in its rheological properties. In this study, we used polarization microscopy to investigate how different mixing methods affect the structure of white petrolatum. We used two different mixing methods, mixing using a rotation/revolution mixer and mixing using an ointment slab and an ointment spatula. The extent of the fragmentation and dispersal of the solid portion of white petrolatum depended on the mixing conditions. Next, we examined the changes in the structure of a salicylic acid ointment, in which white petrolatum was used as a base, induced by mixing and found that the salicylic acid solids within the ointment were also dispersed. In addition to these structural changes, the viscosity and thixotropic behavior of both test substances also decreased in a mixing condition-dependent manner. The reductions in these parameters were most marked after mixing with a rotation/revolution mixer, and similar results were obtained for spreadability. We also investigated the effects of mixing procedure on the skin accumulation and permeation of salicylic acid. They were increased by approximately three-fold after mixing. Little difference in skin accumulation or permeation was detected between the two mixing methods. These findings indicate that mixing procedures themselves affect the utility and physiological effects of white petrolatum-based ointments. Therefore, these effects should be considered when mixing is required for the clinical use of petrolatum-based ointments.

Objective: Objective of the study was to evaluate the effect of Tween 80, palm kernel oil (PKO), and its conversion products (hydrolyzed and transesterificated products) on the in vitro rabbit skin penetration of indomethacin from hydrocarbon ointment base. Materials and Methods: In vitro penetration of indomethacin through hairless rabbit skin from hydrocarbon ointment base (white petrolatum) was evaluated using a diffusion cell. The effects of Tween 80, PKO, and its conversion products at various concentrations were evaluated. Results: The higher of the concentration of Tween 80 until 5%, the higher of the indomethacin penetration. However, at the concentration above 5%, the penetration was decreased with the increasing concentration of Tween 80 used. The amount of indomethacin penetrated increased with the increasing of the concentration of PKO and its conversion products used. Hydrolyzed product showed the higher indomethacin penetration enhancing effect than PKO. Transesterificated product showed the highest penetration enhancing effect. However, the combination of Tween 80 with transesterificated product showed lower penetration enhancing effect compared to transesterificated product only. Conclusion: Tween 80 at low concentrations, PKO, and its conversion products could be used to enhance indomethacin penetration.