• Journal of Pharmaceutical Investigation
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• v.33 no.1
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• pp.1-5
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• 2003

Physicochemical changes of poloxamer-based gel containing capsaicin analog (N-[3-(3,4-dimethylphenyl)propyl]-4-(2-aminoethoxy)-3-methoxyphenyl acetamide) such as drug content, viscosity and surface tension were investigated during the storage conditions at three different temperatures (25, 40 and $60^{\circ}C$) over 90 days. No noticeable changes of color were observed when stored at 25 and $40^{\circ}C$. However, the color of white poloxamer gels turned yellow during storage at $60^{\circ}C$. The drug contents were unchanged during storage at $25^{\circ}C$ but had tendency to decrease at $40^{\circ}C$. The drug contents were highly decreased over 40-50% when stored at $60^{\circ}C$. The viscosity of a poloxamer-based gel was unchanged during storage at 25 and $40^{\circ}C$ but greatly increased at $60^{\circ}C$. The surface tension of a poloxamer-based gel was not changed at three different temperatures. The storage conditions of a poloxamer-based gel containing capsaicin analog can be considered for further clinical applications.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.115-115
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• 1997

A new capsaicin analog modified with 4-hydroxyl and alkyl chain of capsaicin was a very potent antiinflammatory analgesic drug and may be clinically useful for those who have rheumatoid arthritis, diabetic neuropathy and cancer. The purpose of this study was to investigate histopathology after short and long term application of poloxamer-based gels, and percutaneous absorption of various topical formulations. Poloxamer-based gel was prepared by cold method using poloxamer 407. The poloxamer gels was applied to dorsal sites of hairless mouse skin during one week or one month for the evaluation of skin irritation. The applied site was then sectioned for histopathologic examination. The topical formulations were also prepared using CMC, HPMC, MC, carbopol and glycerylmono stearate. Skin variation of poloxamer gels was studied using excised hairless mouse, rat, hamster and human penis skin. Franz-type diffusion cells were used far skin penetration of drug against receptor phase filled with about 10$m\ell$ of 0.9% saline solution kept at 32$^{\circ}C$. The concentration of drug was determined by the reverse phased C18, Symmetry HPLC with fluorometeric detector. No skin erythema was observed after dorsal application of poloxamer-based gels for one week or one month. No histopathologic changes was also examined, suggesting no skin toxicity of poloxamer-based gels. The order of flux rate was HPMC > MC ( CMC > poloxamer >> glycerylmono stearate ( carbopol. There was a skin variation of poloxamer gels. The flux rate of poloxamer gels was highest in case of hairless mouse followed by rat, human and hamster skin. The Partial support-Ministry of Science and Engineering (HAN project).

• YAKHAK HOEJI
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• v.31 no.5
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• pp.280-285
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• 1987

There are three plausible bioconversion pathways in biodegradation mechanism of capsaicinoids; first, side chain degradation through $\omega$-hydroxylation and $\beta$-oxidation, secondly, aromatic ring hydroxylation, and lastly, hydrolysis on the acidaraide linkage. In microbes, it was reported that capsaicin and its synthetic, analog, nonoylvanillylamide(NVA), could be metabolized to N-vanillylcarbamoylbutyric acid via $\omega$-hydroxylation and consecutive $\beta$-oxidations by Aspergillus niger. In order to broaden the scope of microbial degradation of capsaicinoids, over thirty strains of various fungi including Aspergillus, Penicillum, Mycotypha, Gliocladium, Paecilomyces, Byssoclamys, Conidiobolus, Thamnidium, and Entomophthora. It was observed that almost all the strains examined oxidized, the side chain of capsaicids as A. niger did. These observations strongly support the notion that side chain degradation is the most dominant pathway in the microbial degradation of capsaicinoids.

• Journal of Dental Anesthesia and Pain Medicine
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• v.20 no.6
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• pp.337-356
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• 2020

This systematic review focused on the efficacy of topical products in reducing temporomandibular joint disorder (TMD)-associated pain, in comparison to placebo or control interventions. The EMBASE, Web of Science, Cochrane Library, and MEDLINE via PubMed databases were searched for randomized controlled trials (RCTs) using topical interventions in adults diagnosed with TMD. The pain intensity was the primary outcome, and other clinical findings were the secondary outcomes. The risk of bias was evaluated according to the Cochrane's handbook. The search up to February 7, 2020 identified a total of 496 unduplicated references. Nine RCTs with 355 adult patients diagnosed with TMD were included. The meta-analysis did not show a significant reduction in baseline pain intensity in the nonsteroidal anti-inflammatory drug (NSAIDs) group, when compared to the placebo group (P = 0.288). One study demonstrated a statistically significant pain score decrease for Theraflex-TMJ compared to placebo after 10 d of treatment (P = 0.003) and follow-up, 5 d after the last application (P = 0.027). Ping On reduced pain at 4 weeks of application (P < 0.001) but not after 7 d of application (P = 0.136). In one study, cannabidiol (CBD) significantly improved the pain intensity compared to placebo (P < 0.001). However, no differences were found with capsaicin in the two studies (P = 0.465). Evidence was of low quality because the studies were considered as having an unclear or a high risk of bias and a small number of studies were analyzed. The evidence is not sufficient to support the use of topical NSAIDs and capsaicin, and limited evidence was found for Threraflex-TMJ, bee venom, Ping On, and CBD, with only one study reporting for each. Additional studies are recommended to validate these results.

• Archives of Pharmacal Research
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• v.24 no.3
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• pp.224-228
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• 2001

DA-5018, a recently synthesized capsaicin analog, appears to possess potent analgesic activity when administered topically. The objective of this study is to test the feasibility of the topical administration of this compound. Specifically, our goal was to identify vehicle system that permit a reasonable transdermal permeation of the compound in mice. Among the vehicles examined, isopropyl myristate (IPM) showed the largest in vitro permeability across the intact skin (83.6 ${\pm}$ 5.42${\mu}$l/$\textrm{cm}^2$/h ). However, due to the limited solubility of DA-5018 in IPM (0.53 mg/ml), the maximal flux from the IPM medium remained at only 44.3 ${\pm}2.87{\mu}$g/$\textrm{cm}^2$/hr. In order to increase the flux, addition of better solvents for DA-5018 was attempted, under the assumption that flux is the result of both solubility and permeability. Ethoxydiglycol (EG) and oleic acid (OA) were selected as examples of food solvents. The addition of IC or OA to IPM at a 1:1 volume ratio resulted in a comparable increase in the solubility of the compound (i.e., to 61.1 and 50.2 mg/ml for EG and OA, respectively). However, the addition of EG at a 1:1 volume ratio, for example, increased the flux 6.3 fold (i.e., $279{\mu}$g/$\textrm{cm}^2$/hr), while OA, at a 1:1 volume ratio, decreased the flux 5 fold (i.e., $9.26{\mu}$g/$\textrm{cm}^2$//hr). The mechanism of this discrepancy between EG and OA was investigated by measuring the permeabilty of DA-5018 across the stratum corneum-removed skin of the mouse, under the hypothesis that the viable skin layer may serve as a barrier for the permeation of lipophilic substances such as DA 5018. The permeability of DA-5018, from the medium of EG or OA, across the viable skin differed greatly for EG ($0.41{\mu}$l/$\textrm{cm}^2$/hr) and OA ($0.086{\mu}$l/$\textrm{cm}^2$/hr), suggesting that a higher permeability across the viable skin layer is needed for the second solvents. The maximum flux across the intact skin was achieved for DA-5018 when EG was added to IPM at a 1:1 volume ratio. Thus, the use of a binary system appears to be the best approach for realizing the transdermal delivery of DA-5018 at a reasonable rate.

• Journal of the Korean Home Economics Association
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• v.28 no.2
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• pp.31-36
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• 1990

This studies were conducted to find out the possibility of utilizing red pepper seed as resources of food fats, the research method was designed to make a comparison between crude and refined oil, and the results of the studies are as follows : The red pepper seed contained 28% of crude fat and 21% of crude protein. The main fatty acids of red pepper seed oil were linoleic acid(72.10~72.31%), palmitic acid(12.81~13.28%) and oleic acid(9.47~10.48%). The linolenic acid content was so small that is will not influence the autoxidation of the red pepper seed oil. The major triglyceride type of crude and refined oil of red pepper seeds were C52 and C54. The other types were found in a small quantity. The sterol composition of crude oil was $\beta$-sitosterol, campasterol, stigmasteral and brassicasterol,in the quantity order. after refining, brassicasterol was not detected, and the content was decreased by one six and one eight. The toropherol composition of crude and refined oil, tocopherol analog was composed of three kinds $\alpha$-, ${\gamma}$-, $\delta$-, but no $\beta$-form. the quantity of ${\gamma}$-, $\alpha$- and $\delta$-tocopherol were 162.91, 83.72, 43.98mg% respectively. The Quantity of and capsaicin in crude oil was 1,296 ppm, and it was reduced consicerably by refining and removed completely after the process of redeodorization.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.82-86
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• 1997

Pharmacokinetics of a new capsaicin analog, DA-5018 were evaluated after a subcutaneous injection or topical application of $[^{14}C]$--labelled or unlabelled DA-5018 to rats and rabbits. After subcutaneous injection of $_{14}$c-labelled or unlabelled DA-5018, 0.5 mg/kg (equivalent to DA-5018) to rats, the plasma total activity peaked at 2 hr with the terminal half life of 5.34 hr, however, unlabelled-DA-5018 peaked at 1 hr with the terminal half life of 1.26 hr. Moreover, the AUC (0.726 versus 0.2337g hr/ml) and MRT (7.82 versus 3.55 hr) increased significantly based on total radioactivity compared with intact DA-5018. Above data indicated that DA-5018 is extensively metabolized in rats and the terminal half- life of the metabolite(5) had a longer half-life than that of DA-5018. The cumulative percentages of biliary excretion of dose after subcutaneous injection of $[^{14}C]$DA-5018 was 40.2%, however, the value was only 2.14% when unlabelled DA-5018 was injected. After topical application of 0.1% or 0.3% $_{14}$C-labelled or unlabelled DA-5018 cream, 500 mg/kg to rats, the plasma and tissue concentrations except applied skin were under the detection limit. After consecutive 7 days topical application of unlabelled DA-5018, 0.1% and 0.3% cream to rats, the plasma concentrations were also under the detection limit. But the urinary excretion of DA-5018 was significantly increased by repeated topical administration. After topical application of unlabelled DA-5018, 0.1% and 0.3% cream to rabbits, the plasma and urine concentrations were under the detection limit. Above data indicated that the skin permeation of DA-5018 was lower and the metabolism of DA-5018 was higher in rabbits than that in rats.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.5
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• pp.323-338
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• 2022

Burning mouth syndrome (BMS) is a chronic oral disorder of unknown etiology which presents therapeutic challenges. Alpha-lipoic acid (ALA) has been studied as a potential treatment for BMS. The objective of this systematic review and meta-analysis was to evaluate the effectiveness of ALA compared to that of placebo or other interventions in individuals with BMS. Randomized controlled trials (RCT) using ALA to treat BMS were identified from MEDLINE, Cochrane Library, EMBASE, and Web of Science up to February 3, 2021. The assessment of the risk of bias in the included studies was based on the Cochrane guidelines. The primary outcome evaluated was the visual analog scale (VAS) pain intensity. ALA was compared with placebo, clonazepam, gabapentin, pregabalin, ALA plus gabapentin, capsaicin, Biotène^®, and laser therapy. Altogether, 137 records were scanned for inclusion/exclusion, and nine RCTs (two unclear and seven at high risk of bias) were included in the qualitative and quantitative analyses, with a total of 594 patients with BMS included in this review. All studies reported an improvement in VAS pain scores ranging from -0.72 to -2.77. Meta-analysis results showed a non-significant reduction in pain intensity for ALA (P = 0.616) compared to that of placebo on a VAS of 0-10. Patients taking ALA were 1.923 times more likely to show an improvement in self-reported BMS symptoms (P = 0.031) than those in the placebo group. Clonazepam and pregabalin showed a significant VAS pain reduction of 4.08 and 4.68 (P < 0.001), respectively, compared to that with ALA. Although ALA intervention provided a non-significant improvement in the pain score and was more likely to produce a reduction in BMS symptoms, the evidence was of low quality. Further research is needed to establish clear guidelines for the use of ALA for BMS treatment.