The amount of becaplermin to be applied will vary depending upon the size of the ulcer area. Becaplermin should be stored in the refrigerator. [ 1 ]  Analysis of healing human wounds showed that PDGF-BB induces fibroblast proliferation and differentiation and was found to increase healing in patients with decreased healing capacity, such as people living with diabetes. [ 5 ]


Becaplermin must not be used at the site of a  skin cancer . [ 6 ]


The most common side effects in clinical studies were  erythematous rashes . [ 6 ]


A  boxed warning  has been added to the US FDA prescription label to describe an increase rate of death from  cancer  when three or more tubes are used. [ 7 ]


Birch triterpenes , sold under the brand name  Filsuvez , is an extract of  birch bark  used as a  topical medication  for the treatment of  epidermolysis bullosa . [ 1 ] [ 3 ]  The active ingredients are  triterpenes  extracted from the outer bark of  silver birch  ( Betula pendula ) and  downy birch  ( Betula pubescens ). [ 4 ]


The most common side effects include wound complications such as skin reactions at the application site, infections, pruritus (itching), and  hypersensitivity . [ 3 ]


Birch triterpenes was approved for medical use in the European Union in June 2022, [ 3 ]  and in the United States in December 2023. [ 5 ] [ 6 ]


Epidermolysis bullosa is an inherited disease of the skin that makes the skin very fragile and causes severe blistering and scarring. [ 3 ]  Birch triterpenes is used in two types of epidermolysis bullosa,  dystrophic epidermolysis bullosa  and  junctional epidermolysis bullosa , to treat partial-thickness skin wounds. [ 3 ]  These are wounds where the upper layers of the skin have been damaged. [ 3 ]


Birch triterpenes is  indicated  for the treatment of partial thickness wounds associated with dystrophic and junctional epidermolysis bullosa in people aged six months of age and older. [ 1 ] [ 3 ]  The US  Food and Drug Administration  (FDA) considers it to be a  first-in-class medication . [ 7 ]


The most common side effects include wound complications. [ 3 ]  Other common side effects include skin reactions at the application site, wound infections, pruritus (itching), and hypersensitivity (allergic) reactions. [ 3 ]


The active substance of birch triterpenes is birch bark extract (as dry extract, refined) from  Betula pendula  Roth/ Betula pubescens  Ehrh. (equivalent to 0.5‑1.0 g birch bark), including 84‑95 mg triterpenes calculated as the sum of  betulin ,  betulinic acid ,  erythrodiol ,  lupeol , and  oleanolic acid . [ 3 ]  The mechanism of action of birch triterpenes in the treatment of wounds associated with epidermolysis bullosa is unknown. [ 1 ]  It is thought to work by modulating inflammatory mediators and stimulating keratinocyte differentiation and migration, thereby promoting wound healing and closure. [ 3 ]


The pharmacodynamics of birch triterpenes are unknown. [ 1 ]


The US FDA approved birch triterpenes based on evidence from a clinical trial (NCT03068780 [ 1 ] [ 8 ] ) of 223 participants with dystrophic and junctional epidermolysis bullosa. [ 6 ]  The efficacy and safety of birch triterpenes for the treatment of partial-thickness wounds associated with inherited epidermolysis bullosa was evaluated in a randomized, double-blind, placebo-controlled trial in participants aged six months of age and older with dystrophic epidermolysis bullosa and junctional epidermolysis bullosa. [ 6 ]  The primary endpoint was the proportion of subjects with first complete closure of the target wound by day 45 of the 90-day double-blind phase of the study, based on clinical assessment by the investigator. [ 6 ]  The trial was conducted at 49 sites in 26 countries including Argentina, Australia, Austria, Belgium, Brazil, Chile, Colombia, Croatia, the Czech Republic, Denmark, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Romania, Russia, Serbia, Singapore, Spain, Switzerland, the United Kingdom, and the United States. [ 6 ]  There were 14 participants enrolled in the United States and 209 participants were enrolled outside the United States. [ 6 ]


In April 2022, the  Committee for Medicinal Products for Human Use  (CHMP) of the  European Medicines Agency  (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Filsuvez, intended for the treatment of  epidermolysis bullosa . [ 9 ]  The applicant for this medicinal product is Amryt Pharmaceuticals DAC. [ 9 ]  Birch triterpenes was approved for medical use in the European Union in June 2022, [ 3 ] [ 10 ]  and in the United States in December 2023. [ 5 ] [ 11 ] [ 12 ]


Burow's solution  is an  aqueous solution  of  aluminium triacetate . It is available in the U.S. as an  over-the-counter drug  for  topical administration , with brand names including Domeboro (Moberg Pharma), Domeboro Otic (ear drops), Star-Otic, and Borofair. [ 1 ]
The preparation has  astringent  and  antibacterial  properties and may be used to treat a number of skin conditions, including  insect bites and stings ,  rashes  caused by  poison ivy  and  poison sumac ,  swelling ,  allergies , and  bruises . However, its main use is for treatment of  otitis  (ear infection), including  otomycosis  (fungal ear infection). [ 2 ]


The creator of Burow's solution was  Karl August Burow  (1809-1874), a military surgeon and anatomist. Burow was also the inventor of some plastic surgery and wound healing techniques which are still in wide use today. [ 3 ]


Burow's solution may be used to treat various forms of ear infections, known as  otitis . [ 4 ] [ 5 ]  As a drug it is inexpensive and  non-ototoxic . In cases of  otomycosis  it is less effective than  clotrimazole  but remains an effective treatment. [ 6 ]


Most versions of Burow's solution can be used as a soak or compress. As an FDA approved astringent it is used for the relief of skin irritations due to  poison ivy ,  poison oak , and  poison sumac , and rashes from allergic reactions to soaps, detergents, cosmetics and jewelry. [ 7 ]  This is due to the combination of two active ingredients found in this version of Burow's solution, i.e.  aluminum sulfate tetradecahydrate  and  calcium acetate monohydrate . [ 8 ] [ 9 ] [ 10 ]


The solution is used by some to reduce inflammation and potential infection from conditions such as  ingrown nails , in a warm water soak. [ 11 ]


Cosmetic psychopharmacology , a term coined in 1990 by the psychiatrist  Peter D. Kramer  and popularized in his 1993 book  Listening to Prozac , refers to the use of drugs to move persons from a normal psychological state to another normal state that is more desired or better socially rewarded — e.g., from  melancholy  towards assertiveness and confidence or from slower to quicker cognition.


The comparison is with surgery, in which the same intervention can be therapeutic (as in reparative work on burn victims) or cosmetic (as in  rhinoplasty  for the enhancement of beauty in conventional terms). In general, cosmetic psychopharmacology refers to the use of psychoactive medications by normal, healthy individuals for the purpose of enhancement rather than the treatment of a formal pathology. Kramer reported that with the antidepressant  Prozac , occasional patients seemed "better than well," and he discussed the ethical dilemmas that might result if similar medications were offered to individuals not afflicted with psychiatric disorders. Following these case reports, much controversy arose over the veracity and ethics of the cosmetic use of actual  antidepressants  and other similar medications. [ 1 ]


Opponents of cosmetic pharmacology believe that such drug usage is unethical and that the concept of cosmetic pharmacology is a manifestation of naive consumerism. Proponents, such as philosopher  Arthur Caplan , state that it is an individual's (rather than the government's or physician's) right to determine whether to use a drug for cosmetic purposes. [ 2 ]


Anjan Chatterjee, a neurologist at the  University of Pennsylvania , has argued that western medicine stands on the brink of a neuro-enhancement revolution in which people will be able to improve their memory and attention through pharmacological means.  [ 3 ]   Jacob M. Appel , a  Brown University  ethicist, has raised concerns about the possibility of employers mandating such enhancements for their workers. [ 4 ]   [ 5 ]


Crilanomer  is a  cicatrizant .


This  dermatologic   drug  article is a  stub . You can help Wikipedia by  expanding it .


Crocodile oil  is extracted from the fatty tissues of crocodiles.  Crocodile fat  is a product of commercial farming, evident in Thailand. Historically, for centuries crocodile oil has been used by traditional practitioners across the globe, including  Chinese traditional medicine , Southeast Asia, Ancient Egypt.  Crocodile oil has been used since the nineteenth century for different purposes in different cultures. [ 1 ]   Due to the oil's components, its richness in monounsaturated and  polyunsaturated fats , it is sold as ointment for treatment of skin conditions, skin structure enhancement, collagen deposition, and medicine for illnesses. [ 2 ]  In recent times, the use of crocodile oil has invited criticism from the use of crocodile oil as there is an increased demand for cruelty-free and vegan-friendly beauty products in consumers of today's society.


Crocodile oil was used by traditional practitioners for centuries in treatment of ailments, skin conditions, and illnesses such as cancer. [ 3 ]  In  Ancient Egyptian medicine , crocodile oil was used in a liniment to stimulate the growth of hair, to treat bald patches also called  alopecia  as well as prevent grey hair growth. [ 4 ]  Crocodile oil was recognised by the Ancient Egyptians to treat burns when combined with other components such as Egyptian goat fat and lion fat. [ 4 ]  Crocodile oil was also used by the Egyptians to help with trembling in limbs when smeared with other components including honey and olive oil. [ 4 ]  The Papyrus Ebers mentions  Egyptians medicine  recommends the creation of a  vaginal contraceptive  solution composed of crocodile oil,  gum acacia  or honey, and  natron . [ 4 ]  The Historical Table of the Materia Media reports crocodile oil use in  Egyptian Medicine  in creating the ointment with combination of "slime of the nile", frictions of crocodile fat in rheumatism, salt, alum, platters. [ 5 ]  In Africa, crocodile oil is used for ailments such as skin rashes and to promote wound healing. There is also evidence of crocodile oil being used traditionally in South Africa. [ 6 ]  South Africans consult traditional healers, who still play a role in healthcare in rural areas.  Crocodile fat  is mixed with the ground bark of  Cryptocarya latifolia  and used by the  Zulu people  to treat chest ailments. [ 6 ]


Crocodile oil was also used by  Indian Ayurveda medicine  in the nineteenth century for treatment of burns. [ 7 ]   Crocodile oil use in India is recorded in other journals, specifically, the oil is prepared by the Sanif tribe of the Punjab, who eat crocodile fat. [ 8 ]  They [ who? ]  state crocodile oil contains larger amounts of "solidifiable fat" than any fish oil. [ 8 ]  The journal also mentions the oil to be procurable in abundance in Agra. [ 8 ]  Similarly, a journal published by Royal Society of Arts in 1879 discussed the commercial value of crocodile oil as well as how the oil was used in the nineteenth century specifically in Agra, India. [ 1 ]  A Western researcher [ who? ] [ when? ]  determined that crocodile oil contained a larger proportion of solid fat either cod liver or fish oils. They softened the quality of various animal oils on leather and found leather treated with crocodile oil remained stiffer compared to other natural oils. Melted fat of crocodile or crocodile oil was also recorded to be used for "gastric obstructions". [ 9 ]   Nature , in 1886, refers to the use of crocodile oil in Germany for leather dressing, prepared in Punjab and solidified at 33 degrees. [ 10 ]


Chinese traditional medicine as well as Southeast Asian traditional medicine uses crocodile oil and products as ointments for burns and scalds. [ 11 ]  A study tested burn wound-healing efficacy of crocodile oil through a Chinese herbal medicine called crocodile oil burn ointment, consisting of crocodile oil, natural mineral and extraction of other herbal medicines by employing second-degree burns in rats and found crocodile oil enhances burn wound healing capabilities. [ 12 ]  Chinese traditional medicine uses the oil of crocodiles for other conditions such as  bronchitis , allergy, skin problems,  high blood pressure , and cancer. [ 13 ]  Crocodile oil is also prescribed to treat burns, skin ulcers and cancer, coughs, and  asthma  in Madagascar. [ 13 ] [ 14 ]  There is also evidence of crocodile oil being used traditionally in South Africa for skin condition treatments for eczema and rashes and for promoting wound healing. [ 3 ]  Crocodile oil is used in Mexico for treatment of illnesses such as asthma,  emphysema , and  influenza . [ 3 ]


The following tables provides information about the composition of the  fatty acids  in crocodile oil, a more recent and detailed table can be found in Ngernjan  et al. : [ 15 ]


The table below compares acid in crocodile oil and human skin oil:


According to Venter, the composition of  fatty acids  in crocodile oil compared those found in human skin oil indicated that the  palmitoleic acid  (6%),  oleic acid  (39%), and  linoleic acid  (20%) in crocodile oil showed higher percentage than in  human skin  oil. [ 2 ]


Crocodile oil was also used by traditional practitioners to treat skin conditions including  microbial  infections and  inflammatory  conditions. A research by the State Key Laboratory of Marine Environmental Science in China describes the burn wound healing capabilities in crocodile oil indicated by decrease in wound closure time and scar formation in rats. [ 12 ]   The fatty acid profile of crocodile oil indicates that the oil consists mainly of fatty acids that possess antimicrobial and anti-inflammatory properties. [ 3 ]   A research provides scientific evidence of the antimicrobial and anti-inflammatory properties of crocodile oil, compared the use of crocodile oil by traditional healers. [ 12 ]   Their research focused on the study of burn ointment (COBO), topical Chinese herbal medicine (CHM) a compound made from natural mineral, crocodile oil, and extraction of five herbal medicines. [ clarification needed ] [ citation needed ]


The fatty acid profile of crocodile oil indicates that the oil consists mainly of fatty acids that possess antimicrobial and  anti-inflammatory  properties (Kabara  et al. , 1972, Maroon and Bost, 2006).  This study provides novel scientific evidence of antimicrobial and anti-inflammatory properties of crocodile oil, justifying its use by traditional healers.  It highlighted the effects these properties may have when applied as oil or ointment on human skin. A clinical study tested the positive claims of crocodile oil in treatment of ageing skin in comparison to  placebo  lotion. [ 2 ]  They found crocodile oil had "good stability over 6 months period", both lotions showed an increase in skin hydration. [ 2 ]   Venter's research showed no improvement in skin scaliness and elasticity. [ 2 ]  Treatment of  ageing skin  has become very popular over the last decade. Ageing skin is characterised by wrinkles, sagging skin and decreased  laxity . As a result, crocodile oil is used for skin repair to assist in skin quality and appearance as well as skin conditions. According to Croc City, crocodile oil and crocodile oil containing products currently on the market, are used for treatment of  dermatitis , scrapes,  acne ,  razor bumps ,  bed sores ,  haemorrhoids , inflammation of  arthritic  conditions, treatment of discolouration, pigmentation of skin-like brown spots, freckles,  menopausal  darkening, treatment of dry, flaky, itchy and ageing skin,  nappy rash , athlete's foot,  jock-itch  and irritation of head skin. [ 16 ]   Crocodile oil lotion is proven to be a safe product to use on skin. [ 2 ]


With the increase in commercial alligator farming in countries including Thailand, the United States, Australia, South Africa, and  South East Asia , crocodile fat and oil became a commercial product that can be used in a number of ways such as medicine, skin care products, and as a feedstock for  biodiesel . Natural oils are extensively used in cosmetics and as treatment for a growing number of conditions. According to Vermaak, the natural products industry is a multibillion-dollar industry and has grew enormously in the years up to 2011. [ 17 ]  Crocodile oil as an oil mainly containing fatty acids contribute to beneficial properties in cosmetics and personal care products. More specifically, crocodile oil is also used in the tanning industry. [ 18 ]  The oil can range from about $US4 for a tube of crocodile lip balm to about $US104 for a large [ vague ]  jar of pure crocodile oil balm. [ 19 ]  Businesses consider the capability to convert crocodile fat to a marketable oil. They can capitalise on "first-mover advantage" due to crocodile oil benefits. Golden 8 Skincare is an Australian company, using crocodile oil as the main ingredient of its product. [ 20 ]  The company's description of the product include "Packed full of Omegas 3,6 7 and 9 to help in the healing of skin conditions due to its Natural Moisturising Factor (NMF) Crocodile Oil helps prevents dermal irritation and regenerates the skin whilst providing the skin its daily dose of Omegas to produce clear, glowing, healthy skin." [ 20 ]  Crocodile oil lotions and other products derived from crocodile fat can be seen sold online for personal use.


Critics of  Crocodile farming  mentions the use of crocodile oil as a contribution to the diminishing numbers of various crocodile species. [ 21 ]  Many species of crocodile are endangered such as the  Siamese crocodile , [ 22 ]  which is farmed in Thailand. [ 15 ]


According to the  Convention on International Trade in Endangered Species of Wild Fauna and Flora  (CITES), products made from endangered species can be legally traded after certification. [ 23 ]   CITES lists the Nile crocodile under Appendix II which means species are not threatened with extinction, but the collection, processing, domestic trading, and exporting of all crocodile products must be controlled.  Over catching of this animal has led to the decline of this species in wild populations. Efforts are made to preserve the existing habitat of this species. [ 18 ]  Crocodiles have been bred in farms since the early twentieth century, where Thai crocodile farming industry is currently the largest in the world. [ 23 ]   Breeding this animal under captivity is a developing industry in some parts of the world. [ 23 ]


Delgocitinib , sold under the brand name  Corectim  among others, is a  medication  used for the treatment of autoimmune disorders and hypersensitivity, including inflammatory skin conditions. [ 3 ]   Delgocitinib  was  developed  by  Japan Tobacco  and approved in Japan for the treatment of  atopic dermatitis . [ 3 ]   In the United States, delgocitinib is in  Phase III clinical trials  and the  Food and Drug Administration  has granted delgocitinib  fast track  designation for  topical  treatment of adults with moderate to severe chronic hand  eczema . [ 4 ]


Delgocitinib works by  blocking activation  of the  JAK-STAT signaling pathway  which contributes to the pathogenesis of chronic inflammatory skin diseases. [ 5 ]


In July 2024, the  Committee for Medicinal Products for Human Use  of the  European Medicines Agency  adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product
Anzupgo, intended for the treatment of chronic hand eczema. [ 1 ] [ 6 ]  The applicant for this medicinal product is LEO Pharma A/S. [ 1 ]  Anzupgo was approved for medical use in the European Union in September 2024. [ 1 ]


Dextranomer  (trade name  Debrisan ,  Exudex [ 1 ] ) is a  cicatrizant  used in dressings for wound healing, [ 2 ]  and in pharmaceutical products to treat  fecal incontinence . [ 3 ]   It consists of  dextran  polymer chains cross-linked into a three-dimensional network. [ 4 ]


Solesta is the marketed brand name of a system of injections of dextranomer in stabilized  sodium hyaluronate  for use in fecal incontinence (FI). [ 5 ]   This preparation is a biocompatible gel, for use as a  perianal injectable bulking agent . The system is intended to be injected in the submucosal layer of the proximal  anal canal  (i.e. above the level of the  dentate line ).


Diphenylcyclopropenone  ( diphencyprone ) is a  topically administered  experimental drug intended for treating  alopecia areata  and  alopecia totalis . [ 1 ]  Topical immunotherapy using diphenylcyclopropenone may also be an effective treatment option for recalcitrant warts. [ 2 ]   It is not approved by either the  Food and Drug Administration  or the  European Medicines Agency . [ 3 ]


Diphenylcyclopropenone triggers an immune response that is thought to oppose the action of the autoreactive cells that otherwise cause hair loss. [ 4 ]  One hypothesis is that in response to DPCP treatment, the body will attempt to downregulate inflammation through a variety of pathways, resulting in a downregulation of the autoimmune response at the hair follicle. This autoinflammatory reaction would otherwise destroy body's hair follicles. [ 3 ]


A study of 41 alopecia areata patients showed significant hair regrowth in 40% at 6 months, being sustained in two thirds of these after a 12-month-follow up-period. [ 5 ]


In a 2002 study for the treatment of warts, the responders consisted of 135 individuals (87.7%) that had complete clearance of warts. Reported adverse effects were local and included with pruritus (itching) (15.6%), with blistering (7.1%), and with eczematous reactions (eczema)(14.2%). The majority of the patients tolerated the treatment very well. One patient developed local impetigo (minor infection). Patients had an average of 5 treatments over a 6-month period. [ 2 ]


The chemical properties of diphenylcyclopropenone are dominated by the strong  polarization  of the  carbonyl  group, which gives a partial positive charge with  aromatic stabilization  on the cyclopropene ( cyclopropenium ) ring and a partial negative charge on oxygen.  The steric hindrance and partial charge on the cyclopropenium inhibit further  electrophilic aromatic substitution  there, but the phenyl rings are reactive.  The cyclopropenium acts as a  meta  director . [ 6 ]


Electrophilic  Lewis acids  stabilize the charge separation, forming diphenylcyclopropenium ether or ester salts.  Such compounds are extremely reactive electrophiles. [ 6 ]


Conversely, the oxygen is quite nucleophilic.   Lux-Flood acids  can abstract the oxygen: thus activated  isocyanates  effect imines;  phosphorus sulfides  or activated  thioic acids  effect the  thione , [ 6 ]  and a wide variety of electrophilic chlorinators, including  oxalyl chloride ,  thionyl chloride , and  phosphorus pentachloride , effect 3,3‑dichloro-1,2‑diphenylcyclopropene.  The latter sees primary application as an electrophilical chlorinator itself, [ 7 ]  and catalyzes the action of the aforementioned chlorinators. [ 6 ]   However, 3,3‑dichloro-1,2‑diphenylcyclopropene also ligates  palladium  for  cross-coupling reactions , [ 7 ]  and reacts with  trichloroacetate  to give  diphenylcyclobutenedione  upon aqueous  workup . [ 6 ]


In other respects, the carbonyl is a typical  electrophile ,  adding Grignard reagents ,  Knoevenagel enols , and  enamines .  The central ring is highly strained, and the presence of most  transition metals  or heating to 160 °C induces  decarbonylation , although heating just below the decarbonylation temperature (150 °C) irreversibly  forms a [3+2] dimer  instead.  Soft nucleophiles that typically  add in conjugate  typically open the ring instead, as do naïve attempts at reduction.  However, careful  hydroboration  can  reduce away the carbonyl . [ 6 ]


Dixanthogen disulfides  are a class of  organosulfur compounds  with the formula  (ROC(S)S) 2 .  Usually yellow solids, they are the product of the oxidation of  xanthate  salts. [ 1 ]     A common derivative is  diethyl dixanthogen disulfide . Diisopropyl dixanthogen disulfide is commercially available. They are structurally related to  thiuram disulfides .


Diethyl dixanthogen disulfide is a component for  froth flotations  used, inter alia, for the separation of sulfide minerals like  pyrrhotite . Diisopropyl dixanthogen disulfide is a  reagent  in the synthesis of sulfur  heterocycles . [ 2 ]


Dialkoxy dixanthogen disulfides undergo desulfurization by cyanide to give bis(alkoxythiocarbonyl)sulfides: [ 3 ]


Dixanthogens are also  ectoparasiticides .


This  antiinfective   drug  article is a  stub . You can help Wikipedia by  expanding it .


Enoxolone  ( INN ,  BAN ; also known as  glycyrrhetinic acid  or  glycyrrhetic acid ) is a pentacyclic  triterpenoid  derivative of the  beta-amyrin  type obtained from the  hydrolysis  of  glycyrrhizic acid , which was obtained from the herb  liquorice .


The substance has a sweet taste, so it is used in  flavoring  to mask the bitter taste of drugs like  aloe  and  quinine . It may have some anti-inflammatory activities. [ 1 ]  One of its metabolites is responsible for the blood pressure-increasing effect of liquorice. [ 2 ]


In Turkey, enoxolone is used in a "Anzibel" lozenge in combination with  benzocaine  (a local anesthetic) and  chlorhexidine  hydrochloride (an antibacterial). [ 3 ]


It is found in an over-the-counter "Arthrodont" toothpaste. Evidence for the ingredient's usefulness for plaque and gingivitis is lacking. [ 4 ]


In Japan, enoxolone is found in the " Salonpas " pain-relief menthol patch. [ 3 ]


It is also used in the Singaporean "Vetic" cream. [ 3 ]  In the United States, it is found in PruClair, a "precription medical device" indicated for generic  dermatoses . [ 5 ]


Enoxolone is effective in the treatment of  peptic ulcer  and also has  expectorant  (antitussive) properties. [ 1 ]   It has some additional pharmacological properties with possible antiviral, antifungal, antiprotozoal, and antibacterial activities. [ 6 ] [ 7 ] [ 8 ] [ 9 ]


Glycyrrhetinic acid inhibits the  enzymes  ( 15-hydroxyprostaglandin dehydrogenase  and delta-13-prostaglandin) that metabolize the  prostaglandins  PGE-2 and PGF-2α to their respective, inactive 15-keto-13,14-dihydro  metabolites . This increases prostaglandins in the digestive system. Prostaglandins inhibit gastric secretion, stimulate  pancreatic  secretion and mucous secretion in the  intestines , and markedly increase intestinal motility. They also cause cell proliferation in the  stomach . The effect on  gastric acid  secretion, and promotion of mucous secretion and cell proliferation shows why licorice has potential in treating peptic ulcers. [ 10 ]


Licorice should not be taken during pregnancy, because PGF-2α stimulates activity of the uterus during pregnancy and can cause abortion. [ citation needed ]
ds
The structure of glycyrrhetinic acid is similar to that of  cortisone . Both molecules are flat and similar at positions 3 and 11. This might be the basis for licorice's  anti-inflammatory  action. [ citation needed ]


3-β- D -(Monoglucuronyl)-18-β-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid, inhibits the conversion of 'active'  cortisol  to 'inactive'  cortisone  in the  kidneys . [ 11 ]  This occurs via inhibition of the enzyme  11-β-hydroxysteroid dehydrogenase . [ citation needed ]  As a result, cortisol levels become high within the collecting duct of the kidney. Cortisol has intrinsic mineralocorticoid properties (that is, it acts like  aldosterone  and increases  sodium  reabsorption) that work on ENaC channels in the collecting duct.  [ citation needed ]   Hypertension  develops due to this mechanism of sodium retention. People often have high blood pressure with a low  renin  and low  aldosterone  blood level. [ citation needed ]  The increased amounts of cortisol binds to the unprotected, nonspecific mineralocorticoid receptors and induce sodium and fluid retention,  hypokalaemia , high blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Therefore, licorice should not be given to patients with a known history of hypertension in doses sufficient to inhibit 11-β-hydroxysteroid dehydrogenase. [ 2 ]


In glycyrrhetinic acid, the  functional group  ( R ) is a  hydroxyl  group. Research in 2005 demonstrated that with a proper functional group a very effective glycyrrhetinic  artificial sweetener  can be obtained. [ 12 ]  When  R  is an  anionic  NHCO(CH 2 )CO 2 K  side chain , the sweetening effect is found to be 1200 times that of  sugar  (human sensory panel data). A shorter or longer  spacer  reduces the sweetening effect. One explanation is that the  taste bud  cell  receptor  has 1.3  nanometers  (13  angstroms ) available for docking with the sweetener molecule. In addition, the sweetener molecule requires three  proton  donor positions, of which two reside at the extremities, to be able to interact efficiently with the receptor cavity.


A synthetic analog,  carbenoxolone , was developed in Britain.  [ citation needed ]  Both glycyrrhetinic acid and carbenoxolone have a modulatory effect on neural signaling through  gap junction  channels.


Acetoxolone , the  acetyl  derivative of glycyrrhetinic acid, is a drug used in the treatment of  peptic ulcer  and  gastroesophageal reflux disease .


EpiCeram  ( EpiCeram Skin Barrier Emulsion ) is a topical non-steroidal  skin cream .
Based on the research of Peter M. Elias, [ 1 ]  it is made up of  ceramides , free  fatty acids , and  cholesterol , and is designed to treat  atopic dermatitis , [ 2 ]  a type of  eczema . [ 3 ] [ medical citation needed ]   Ceragenix  obtained marketing clearance from the  U.S. Food and Drug Administration  in April 2006. [ 4 ]  This prescription medical device [ 5 ] [ failed verification ]  works as a  moisturizer  and barrier cream. In the US, it requires prescription and was launched in October 2008 by Promius Pharma. [ 1 ]  EpiCeram was acquired by PuraCap Pharmaceutical LLC in 2010.


EpiCeram obtained  Health Canada  medical device license in September 2009 and was launched by  Pediapharm  in November of the same year. It is sold under  prescription .


Ethyl lauroyl arginate  ( LAE ) is a  food preservative ,  antimicrobial  compound, and drug more commonly known as  E243 . [ 1 ] [ 2 ] [ 3 ] [ 4 ]  It is used to treat  dermatological  disorders [ 2 ]  and is often provided in the form of its  hydrochloride  salt. LAE is an  amino acid -based  surfactant  with broad-spectrum antimicrobial activity, high biodegradability and low toxicity. Due to these features, LAE is a preservative used in food and cosmetic formulations.


The first synthesis of ethyl lauroyl arginate hydrochloride and its antimicrobial properties were reported in 1976. In the earlies 1980s, LAMIRSA together with Consejo Superior de Investigaciones Científicas (CSIC, Barcelona) began to investigate a new approach to the control of pathogens in food through the application of cationic surfactants based on natural building blocks that inhibit the proliferation of a huge variety of microorganisms, including Gram-positive and Gram-negative bacteria, moulds and yeasts. In 1995 LAMIRSA together with CSIC patented a new process to synthesize LAE. [ 4 ]


LAE is a white solid, soluble in deionized water up to 247 g/kg at 20 °C with a melting point from 57 °C to 58 °C. Its partition coefficient between olive oil and water is 0.07; it allows LAE to be located in the water fraction, which is more susceptible to microbial contamination. [ 5 ]  This property gives LAE an advantage over other preservatives with a different chemical structure intended for the same applications.


LAE shows chemical stability at a pH range between 3 and 7 [ 6 ] [ 7 ]  and maintains its antimicrobial activity in this interval.


Its low toxicity and remarkable antimicrobial features make LAE a product with a wide application within the food and cosmetic preservation fields. The use of LAE means a great technological innovation toward manufacturing products with better preservation qualities. In this connection, MIRENAT is a range of formulated products based on LAE intended for the food industry. At the same time, AMINAT is a range of formulated products based on LAE intended for the cosmetic industry.


MIRENAT range of products reduces the risk of food spoilage as it diminishes the presence of pathogens such as  Listeria monocytogenes ,  Salmonella spp.,  and  Escherichia coli . MIRENAT also prolongs the shelf life of food products because of its broad spectrum of activity against all types of microorganisms. Furthermore, it does not modify the organoleptic properties of the treated products.


The antimicrobial activity of LAE solutions applied in food has been widely studied. For instance, Luchansky  et al.  studied the preservation of commercially prepared ham using LAE solutions. [ 8 ]  Initially, hams were surface inoculated with a five-strain cocktail of  Listeria monocytogenes  (7 log 10  CFU/ ham), added to shrink-wrap bags that already contained LAE, vacuum-sealed, and stored at 4 °C for 24 h. In samples treated with 2, 4, 6, and 8 mL of 5% Mirenat-N ( i.e.,  0.5% of LAE), pathogen levels decreased dramatically by 5.1, 5.4, and 5.5 log 10  CFU/ham. In addition, samples treated with 8 mL of 5% Mirenat-N for 28 days of refrigerated storage still showed pathogen levels below the limit of detection ( i.e.,  1.48 log10). Similar assays were also conducted using an initial inoculum of 3 log 10  CFU/ham. Here, samples treated with 2, 4, 6, and 8 mL of 5% Mirenat-N and stored at 4 °C for 24 h showed pathogen levels below the detection limit for all volumes assayed. Furthermore, samples treated with 6 and 8 mL of 5% Mirenat-N for 28 days of refrigerated storage still showed pathogen levels below the detection limit.


Soni  et al.  also studied the reduction of  Listeria monocytogenes  in cold-smoked salmon by LAE. [ 9 ]  The authors reported that treatment of cold-smoked salmon containing 3.5 log 10  CFU/cm 2   Listeria monocytogenes  with LAE (200 ppm) showed strong listericidal action. Thus, treatment with 200 ppm LAE at 4 °C yielded 2.7 and 5.5 log 10  CFU mL −1  reduction after 1 h and 4 h incubation, respectively. After 24 h incubation at 4 °C, no  Listeria monocytogenes  survival was recovered. At 30 °C,  Listeria monocytogenes  reductions were 3.8, 7.0, and 8.0 log 10  CFU mL −1  after 1 h, 4 h, and 24 h incubation treatment, respectively.


AMINAT range of products are preservatives for personal care products such as cosmetic creams, lotions, body milks, hair conditioners, and sunscreen formulas or can be used as an active ingredient in soaps, anti-dandruff shampoos, deodorants, and oral care products. AMINAT combines a high antimicrobial efficacy with innocuousness, non-sensitizing, and non-skin irritating features. It also provides smoothness to skin and hair because of its cationic nature.


AMINAT is an environmentally acceptable cosmetic ingredient with the certifications Ecocert, Cosmos, and Natrue.


Vedeqsa scientists evaluated the activity of LAE in anti-dandruff applications. [ 10 ]  The authors performed suspension tests to compare the antimicrobial activity  in vitro  of several formulations against  Malassezia furfur , yeast involved in the proliferation of dandruff. The results demonstrated that the action of the shampoo containing LAE was comparable to the shampoo containing the active zinc pyrithione and slightly superior to that of the shampoo containing the active piroctone olamine.  In vivo  assays were also performed. Thus, a dermatologist evaluated the dandruff severity of twenty volunteers before and after a four-week treatment. Shampoo containing LAE showed comparable or superior performance to the classic anti-dandruff active agents, with a better toxicological and eco-toxicological profile. The authors also evaluated the activity of LAE in anti-acne applications. Here, suspension tests were performed to compare the antimicrobial activity  in vitro  of several dermo-purifying gels against  Propionibacterium acnes , a Gram-positive bacterium involved in acne formation. Results revealed that gels containing LAE had a quicker killing effect than gels containing other active ingredients such as salicylic acid or δ-gluconolactone. The  in vivo  activity of gel containing LAE was assayed in eleven volunteers with greasy and acne-prone skin for 28 days by applying 1 mL of the gel. The results showed a significant reduction in the number of pimples for each volunteer during the treatment. Furthermore, a 13.5% decrease in the average amount of sebum measured on volunteers showed a sebolytic effect of the gel containing LAE as an active.


LAE has potential in treating  gingivitis , and the more advanced  periodontitis . In a study comparing ethyl lauroyl arginate in 0.147% mouthwash to  chlorhexidine  0.12% as an adjunctive therapy in the non-surgical treatment of periodontitis, the results showed there were no treatment-related adverse events. Total bacterial count and the specific pathogens were reduced at 4 weeks and 3 months by both mouthwashes with no statistical differences between them at neither periods of time. It was concluded that 0.147% LAE-containing mouthwash could be an alternative to the use of 0.12% chlorhexidine in the non-surgical therapy of periodontitis considering the similar clinical effects, more stable microbiological improvement and absence of adverse effects. [ 11 ]


It is sold as the main active ingredient in  Listerine  Advanced Defence Gum Treatment [ 12 ]  and as one of the active ingredients in GUM Activital Mouthwash. [ 13 ]


Researchers from the Systems Immunity University Research Institute, Division of Infection & Immunity, School of Medicine in Cardiff, UK were studying the virucidal properties of several mouthwashes against SARS-CoV-2. The study, first published in November 2020, noted that mouthwashes containing LAE eradicated the virus completely, giving >5-log10 reduction in viral titres, surpassing the level required for  EN14476 .


"Two  CPC -containing mouthwashes (Dentyl Dual Action and Dentyl Fresh Protect) and a mouthwash containing 23% v/v ethanol/LAE (Listerine® Advanced DGT) eradicated the virus completely, giving >5-log10 reduction in viral titers and thus met EN14476 as a virucide." [ 14 ]  "Aqueous solutions of LAE below (3.3 mM) and above (9.9 mM) the critical micelle concentration (cmc, 4.9 mM), completely eradicated SARS-CoV2, mirroring the potent antiviral activity of Listerine® Advanced DGT, which contains 3.3 mM LAE (Fig. 5B). This was seen with or without 23% ethanol inclusion, indicating that LAE is responsible for the antiviral activity of this product. To determine the potential effect of charge on molecular interactions with the viral lipid membrane, in addition to CPC and LAE (cationic surfactants), the effect of the anionic surfactant dodecylbenzensulfonate was tested and found to completely eradicate infectivity (Fig. 5B)." [ 14 ]


The authors noted several studies on the impact of surfactant-based oral and nasal rinsing: "Furthermore, a recent small study [ 15 ]  suggested that oral rinsing could shorten hospital stay, whereas another study suggested that oral and nasal rinsing could reduce both disease and symptoms in health care professionals. Recently, World Health Organization included a recommendation that  PVP-I  could be used to reduce the risk of clinical transmission in dentistry. [ 16 ] "


Due to its basic guanidine group, LAE is a cationic surfactant. The target of cationic surfactants is the bacterial cytoplasmic membrane, which carries a negative charge often stabilized by the presence of divalent cations such as Mg 2+ and Ca 2+ . Initially, the cationic surfactant crosses the cell wall ( i.e.,  external cell envelopes) of bacteria. Then, the antimicrobial agent displays a high binding affinity for the outermost surface of the cytoplasmic membrane ( i.e.,  inner cell envelope).  Later, the cationic surfactant's alkyl chain penetrates into the membrane's hydrophobic core. This leads to a progressive leakage of cytoplasmic material, perturbating their metabolic processes, and the normal bacterial cycle is inhibited. Thus, cationic surfactants are considered a "membrane-active agent". [ 17 ] [ 18 ] [ 19 ]


Dra. Manresa  et al.  investigated the effects caused by LAE in  Salmonella typhymurium  and  Staphylococcus aureus . LAE caused disturbance in membrane potential and structural changes and loss of cell viability. However, no disruption of cells was detected. [ 20 ]  Similar effects were also observed on two food-related bacteria such as  Yersina enterolitica  and  Lactobacillus plantarum . Here, flow cytometry, transmission electron microscopy, and potassium leakage assays demonstrated that LAE targets the cytoplasmic membrane causing loss of membrane potential and potassium ions. [ 21 ]


The following tables [ clarification needed ]  show the minimum inhibitory concentrations of LAE against different types of microorganisms, primarily pathogens, giving insight into LAE's broad spectrum antimicrobial activity and great effectiveness. Dr. Manresa evaluated the antimicrobial activity of LAE in the Faculty of Pharmacy of the University of Barcelona. [ 22 ]


Further information concerning the antimicrobial properties of LAE is available at  [ 23 ]


On 1 September 2005, the United States Food and Drug Administration issued the No Objection Letter that LAE is Generally Recognized as Safe for use as an antimicrobial in several food categories at levels up to 200 ppm. Besides, the USDA (United States Department of Agriculture) approved its use in meat and poultry products. LAMIRSA submitted both petitions.


In July 2006 and ratified in July 2012, the Health Secretary of Mexico (Secretaría de Salud) published in its Official Journal that lauric arginate is an allowed substance to be used as a food additive for human consumption.


The EFSA (European Food Safety Authority) evaluated this new additive with a favorable opinion in April 2007 and, in July 2013, assigned it the number E-243. In May 2014, Regulation 506/2014 was published, authorizing a maximum dosage level of 160 ppm for its use in cooked meat products.


In August 2014, Health Canada amended the food legislation to include LAE as a preservative in various foods at a maximum dosage level of 200 ppm.


The Joint FAO/WHO Expert Committee on Food Additives (JECFA) evaluated LAE at its 69th meeting in June 2008. JECFA, a body dependent on WHO (World Health Organization), established an acceptable daily intake of 4 mg/Kg bw for the active material. Codex Alimentarius approved LAE use in several food matrixes up to 200 ppm in July 2011.


In March 2015, LAE was included in the IPA database (Inventory of Substances used as Processing Aids) of the CCFA (Codex Committee on Food Additives) as a processing aid in meat products, poultry, and game.


In March 2016, the CCFA issued a positive evaluation of LAE use in several food categories of meat and poultry. In July 2016, the Codex Alimentarius Commission included these approvals at the 39th meeting.


During the 50th session of the CCFA in March 2018, the proposed uses in food categories of fishery products were accepted. It is expected to be approved by Codex Alimentarius Commission at its 41st meeting scheduled for July 2018.


Other countries where the use of lauric arginate is also approved are Colombia (October 2009), Australia and New Zealand (April 2010), Vietnam (November 2012), Chile (August 2013), Israel (November 2014), Turkey (November 2013) and United Arab Emirates (April 2015), India (2011).


Most recently, the Food Safety and Standards Authority of India (FSSAI) included in 2018 similar uses and food categories previously recognized by CODEX in 2011. Finally, a request for the use of LAE as a processing aid antimicrobial treatment on raw meat was made to the Government of Canada (Health Canada), resulting in a Letter Of No Objection (LONO) issued in December 2022.


In addition to food applications, LAE has exceptional properties to be used as a cosmetic preservative/active ingredient for a wide range of cosmetic products.


As a cosmetic preservative, LAE was approved in the EU in 2009 according to the Cosmetic Directive to be used up to 0.4% for cosmetic products (except for lips, oral, and spray products) and up to 0.15% in mouthwashes (not children < 10 years). As an active cosmetic ingredient, it was also approved to be used up to 0.8% in soaps, anti-dandruff shampoos, and deodorants (not in spray).


In the same way as EU approval for cosmetic applications, LAE is also confirmed to be used in the US, Mexico, Canada, Australia, New Zealand, South Korea, and Japan, with similar applications and reference doses.


In conjunction with its remarkable antimicrobial features, the low toxicity makes LAE a product with a wide application within the food and cosmetics preservation fields. The addition of LAE means a great technological innovation toward manufacturing products with better preservation qualities.


To many customers, the claim, "no preservative added", often has the false connotation of improved quality. However, proper use of food preservatives can benefit the safety and quality of food.


A series of toxicological experiments carried out by Huntingdon Life Science, Ltd. [ 24 ]  confirmed the safety of LAE tests, included the metabolism of LAE in animals and humans, mutagenic, acute, subchronic, chronic, reproductive, and developmental toxicity. The results of these studies have been published in the prestigious scientific journal  Food Chemical Toxicology . [ 25 ]


Rats were administered an oral dose of  14 C-LAE (arginine portion of LAE uniformly radio-labeled) to assess the absorption, distribution, metabolism, and excretion (ADME) of LAE.


Once  14 C -LAE was administered to rats, the biotransformation of LAE was followed through the absorption and excretion rates. [ 26 ]  The excretion rates were determined through the analysis of urine, faeces, and air exhalation, the routes of radioactivity elimination from the body. The following figure (Figure 1) summarises the excretion of radioactivity and the percentage retained in the carcass:


The results in Figure 1 show that approximately 50% of the  14 C -LAE administered was absorbed and remained in the carcass of rats, including the liver and gastrointestinal tract.


The next task was to identify and quantify the specific radioactive compounds present in the rats' plasma and define the toxicokinetics based on an  in vivo  study of metabolism. [ 27 ]


Figure 2 reports the percentage of radioactive compounds present in samples of plasma extracted over 4.5 hours after administering  14 C-LAE to rats. LAE is rapidly metabolised to  N α -lauroyl-L-arginine (LAS) and then to arginine, which is more slowly metabolised to ornithine. Ornithine is transformed into endogenous products via the urea and citric acid cycles.


The metabolism experiments' results help to establish a biotransformation mechanism for LAE after ingestion. Figure 3 is the proposed pathway of LAE degradation by which it is rapidly hydrolyzed either by loss of the lauroyl side chain to form arginine ethyl ester and/or cleavage of the ethyl ester to form  N α -lauroyl-L-arginine (LAS).


Further hydrolysis of either intermediate results in the generation of arginine, which is then further hydrolyzed to ornithine and urea. Ornithine can be incorporated into the organisms via the urea and citric acid cycles until final degradation to CO 2 . This metabolic pathway (Figure 4) and the supporting data were presented to the ISSX International Congress in Munich in 2001. [ 28 ]


The cream containing the  drug  combination  fluocinolone acetonide/hydroquinone/tretinoin  (trade name  Tri-Luma ) is used for the treatment of  melasma  (dark skin patches).It is marketed by  Galderma . [ 1 ] [ 2 ]  In China, this generic drug with the same ingredients is sold under the trade name "Fumeida ®  （孚美达 ® 乳膏）" [ 3 ]   [ 4 ] and exclusively manufactured and marketed by  Zhejiang Fonow Medicine Co., Ltd. （浙江孚诺药业股份有限公司） [ 5 ]


Fluocinolone acetonide (0.01%)/Hydroquinone (4%)/ Tretinoin (0.05%) Cream is indicated for the short-term (up to 8 weeks) treatment of moderate to severe melasma of the face in the presence of measures for sun avoidance, including the use of sunscreens.  [ 6 ]  Tri-Luma is the only FDA-approved drug containing hydroquinone, [ 7 ]  a prescription product approved for the short-term treatment of dark spots associated with moderate-to-severe melasma of the face. FA+HQ+RA  is effective in patients of all races/ethnicities and Fitzpatrick skin types. [ 8 ]


Some patients may have very severe allergic reactions to Tri-Luma Cream  due to the sulfites contained in the product. In some cases, these allergic reactions may result in severe asthma attacks, which can be life threatening.
While you use Tri-Luma Cream, your skin may develop mild-to-moderate redness, peeling, burning, dryness, or itching.


Tri-Luma Cream contains a corticosteroid medicine as one of its active components.  The following side effects have been reported with application of corticosteroid medicines to the skin: itching, irritation, dryness, infection of the hair follicle, acne, changes in skin color, inflammation around the mouth, allergic skin reaction, skin infection, skin thinning, stretch marks and sweat problems.
In addition, Tri-Luma Cream contains a corticosteroid that may produce reversible effects on the adrenal gland called hypothalamic-pituitary-adrenal (HPA) axis suppression, so tell your doctor if you have any condition that may affect your adrenal function, such as Addison’s disease.
Some patients using Tri-Luma Cream develop dark spots on their skin, tingling, increased skin sensitivity, rash, acne, skin redness caused by a condition called rosacea, skin bumps, blisters, or tiny red lines or blood vessels showing through the skin. Tri-Luma Cream may also cause a gradual blue-black darkening of your skin. [ 9 ]


The most common side effects ： [ 10 ]
• redness
• dryness
• peeling
• itching
• burning
• acne


Hydroquinone
Several hypotheses exist to explain the action of hydroquinone in skin lightening.It may interrupt one or more steps in thetyrosine-tyrosinase pathway of melanin synthesis,thus inhibit-ing the conversion of tyrosine to melanin.It compromises the formation of melanosomes and destroys the membranous structures of melanocytes,which results in their degradation.It has also been shown that hydroquinone affects fundamental aspects of cellular metabolism and that melanocytes are partic-ularly vulnerable.Hydroquinone may be oxidized by tyrosi-nase to form toxic compounds.Even low concentrations can cause decreases in DNA and RNA synthesis in melanotic cells.
 Tretinoin
Tretinoin (retinoic acid)causes dispersion of pigment granules in keratinocytes,interferes with pigment transfer,and acceler-ates epidermal transfer,thus causing pigment to be lost more rapidly.Tretinoin also accelerates epidermal turnover,shorten-ing the "transit time"from the basal layer and accelerating pig-ment loss.Retinoic acid reduces epidermal melanin,possibly by decreasing the rate of transfer of melanosomes to ker-atinocytes,secondary to an increase in epidermal proliferation and tyrosinase inhibition and a resultant reduction in melano-genesis.
 Corticosteroid
Corticosteroids have anti-metabolic effects on many cell sys-tems.They are cytotoxic or cytostatic for the epidermis anddecrease epidermal turnover. [ 11 ]


Kligman formula consisting of 0.1% tretinoin, 5.0% hydroquinone, 0.1% dexamethasone, and hydrophilic ointment. [ 12 ]  The dermatologist gold-standard formula for treating hyperpigmentation is the Kligman formula, a prescription named after its inventor, dermatologist Dr. Albert Kilgman. It was originally formulated in 1975 and has remained the most effective topical treatment formula for fading dark spots ever since.  [ 13 ]


Ingenol mebutate , sold under the brand name  Picato , is a substance that is found in the sap of the plant  Euphorbia peplus , [ 1 ]  commonly known as petty spurge, and is an inducer of  apoptosis . This compound was isolated first from this plant in 2000. [ 2 ]  A gel formulation of the drug has been approved by the U.S.  Food and Drug Administration  (FDA) [ 3 ]  and by the  European Medicines Agency  (EMA) [ 4 ]  for the topical treatment of  actinic keratosis . Two different strengths of the gel have been approved for use on either the face and scalp (0.015%) or the trunk and extremities (0.05%), respectively. [ 5 ]  In 2020 the drug was withdrawn from the market in the EU. [ 6 ]


Irritation of the application site is very common. The various types of irritation include redness, scaling, crusting, pain, severe itching, and sometimes infection. Additional possible side effects include eye irritation, such as  periorbital edema  (3% of patients in studies), headaches (2%) and  nasopharyngitis  (running nose, 2%). [ 7 ]


Allergic reactions,  shingles , changes in pigmentation at application site, chemical conjunctivitis, and corneal burns may also occur. [ 8 ] [ 9 ]


The  European Medicines Agency  recommended suspending the marketing authorisation of ingenol mebutate due to concerns regarding increased incidence of skin cancer in patients treated with topical ingenol mebutate compared to  vehicle  or  imiquimod . Physicians were advised to refrain from prescribing ingenol and to use different treatment options. [ 10 ]  Subsequently, the marketing authorization holder requested withdrawal of the manufacturing authorization for commercial reasons. The withdrawal was granted and therefore, ingenol mebutate is no longer registered in the EU. [ 6 ]


As ingenol mebutate is not effectively absorbed through the skin and into the bloodstream, interactions with oral drugs are unlikely. [ 11 ] [ 12 ]


The substance is an  ester  of the  diterpene  ingenol and  angelic acid .  A 3-step semisynthesis of ingenol mebutate starting from ingenol was described by a chemical research group in Denmark in 2012. [ 13 ]  A 14-step synthesis of (+)-ingenol from  (+)-3-carene , which is a relatively inexpensive constituent of  turpentine , was published in July 2013. [ 14 ]


The mechanism by which ingenol mebutate causes cell death is still not fully understood.  One study on squamous cell carcinoma, the precursor of which is actinic keratosis, cultures found that the PKC/MEK/ERK signaling pathway is involved in causing cell death after treatment with ingenol mebutate.  In addition, the interleukin decoy receptors IL1R2 and IL13RA2 were induced, resulting in a reduction in the long-term viability of the cells, which could help prevent recurrence. [ 15 ]


Results from four multicenter, randomized, double-blind studies have shown that ingenol mebutate gel applied topically, for 2 to the trunk or 3 days to the face or scalp, is effective for field treatment of actinic keratoses. [ 16 ] [ 11 ]


A twelve-month follow-up study was performed on actinic keratosis patients who had been treated with ingenol mebutate, 108 of which had been treated for face or scalp and 71 for trunk or extremities and the study found that of those treated for the face or scalp 46.1% had sustained clearance, and of those treated for the trunk 44.0% had sustained clearance for the period of the study. [ 17 ]


Ingenol mebutate has also been found to be useful for reactivating latent  HIV  virus in cells taken from individuals who have tested negative for signs of the disease following extended courses of anti-retroviral drugs, raising the possibility that this drug may be used to expose the last traces of virus, and thus potentially provide a permanent cure for HIV infection. Research is ongoing to determine whether the effects observed  in vitro  are also seen in animal models, with a view to eventual human trials for this application. [ 18 ]


A placebo-controlled study on hairless mice found that 0.1% ingenol mebutate gel was able to remove two-week-old tattoos consistently.  It was observed that the microspheres within the skin containing the dye would exude into the scab intact and slough off as the skin healed about 20 days after treatment began. This mechanism appears to be independent of ink color, unlike laser tattoo removal, which is less effective for certain colors. There are no reports of human trials having been conducted. [ 19 ]


Health Canada assessed twelve studies published in scientific and medical literature in order to determine the link between the use of ingenol mebutate and skin cancer. Health Canada's review found that six of the twelve studies had evidence of skin cancer with the use of ingenol mebutate. The European Medicines Agency (EMA) has also reviewed this safety issue. In April 2020, it concluded that ingenol mebutate may increase the risk of skin cancer and that its risks outweigh its benefits. On 11 February 2020, the manufacturer voluntarily withdrew the product from the European Union market. [ 20 ]


Jasminum officinale , known as the  common jasmine  or simply  jasmine , is a species of  flowering plant  in the olive  family  Oleaceae. It is native to the Caucasus and parts of Asia, also widely naturalized.


It is also known as  summer jasmine , [ 1 ]   poet's jasmine , [ 2 ]   white jasmine , [ 2 ]   true jasmine  or  jessamine , [ 2 ]  and is particularly valued by gardeners throughout the  temperate  world for the intense fragrance of its flowers in summer. It is also the  National flower  of  Pakistan .


Jasminum officinale  is a vigorous, twining  deciduous   climber  with sharply pointed  pinnate  leaves and clusters of starry, pure white flowers in summer, which are the source of its heady scent. [ 3 ]  The leaf has 5 to 9 leaflets. [ 4 ]


The Latin  specific epithet   officinale  means "useful". [ 5 ]


It is found in the Caucasus, northern Iran, Afghanistan, Pakistan, the Himalayas, Tajikistan, India, Nepal and western China ( Guizhou ,  Sichuan ,  Xizang  (Tibet),  Yunnan ). The species is also widely cultivated in many places, and is reportedly naturalized in Spain, France, Italy, Portugal, Romania, Croatia, Bosnia and Herzegovina, Montenegro, Serbia, Algeria, Florida and the West Indies. [ 3 ]


J. officinale  has been found to contain alkaloids, coumarins, flavonoids, tannins, terpenoids, glycosides, emodine,  leucoanthocyanins , steroids, anthocyanins, phlobatinins,  essential oil  and saponins. [ 6 ]


Jasminum officinale  is so ancient in cultivation that its country of origin, though somewhere in  Central Asia , is not certain. [ 7 ]  H.L. Li,  The Garden Flowers of China , [ 8 ]   notes that in the third century CE, jasmines identifiable as  J. officinale  and  J. sambac  were recorded among "foreign" plants in Chinese texts, and that in ninth-century Chinese texts  J. officinale  was said to come from  Byzantium . Its Chinese name,  Yeh-hsi-ming  is a version of the Persian and Arabic name. [ 9 ]


Its entry into European gardens was most likely through the Arab-Norman culture of Sicily, but, as the garden historian John Harvey has said, "surprisingly little is known, historically or archaeologically, of the cultural life of pre-Norman Sicily". [ 10 ]  In the mid-14th century the  Florentine  author  Boccaccio  in his  Decameron  describes a  walled garden  in which "the sides of the alleys were all, as it were, walled in with roses white and red and jasmine; insomuch that there was no part of the garden but one might walk there not merely in the morning but at high noon in grateful shade." [ 11 ]  Jasmine water also features in the story of Salabaetto in the  Decameron . [ 12 ]   Jasminum officinale , "of the household office" where perfumes were distilled, was so thoroughly naturalized that  Linnaeus  thought it was native to Switzerland. [ 13 ]  As a garden plant in London it features in  William Turner 's  Names of Herbes , 1548.


Double forms, here as among many flowers, were treasured in the 16th and 17th centuries.


Numerous  cultivars  have been developed for garden use, often with  variegated  foliage. The cultivar 'Argenteovariegatum', [ 14 ]  with cream-white  variegation  on the leaves, has gained the  Royal Horticultural Society 's  Award of Garden Merit . [ 15 ]


The  essential oil  of  Jasminum officinale  is used in  aromatherapy . Jasmine  absolute  has a heavy, sweet scent valued by perfumers. The flowers release their perfume at dusk, so flowers are picked at night and a tiny amount of oil is obtained from each blossom by solvent extraction. The result is an expensive oil which can be used in low concentrations. [ citation needed ]


Jasmine is " generally recognized as safe " (GRAS) as a food ingredient by the U.S.  Food and Drug Administration . [ 16 ]


It is unknown whether jasmine consumption affects breastmilk, as the safety and efficacy of jasmine in nursing mothers or infants has not been adequately studied. [ 16 ]  Drinking small amounts of jasmine tea likely are not harmful during nursing. [ 16 ]


Allergic reactions  to jasmine may occur. [ 16 ]


Maxacalcitol  (trade name  Oxarol ) is a  vitamin D 3  analog and  vitamin D receptor  activator (VDRA). [ 1 ]  As a pharmaceutical drug, it is used as an injection to treat  secondary hyperparathyroidism  resulting from  hemodialysis  and as a topical ointment for  psoriasis . [ 2 ]


It was approved for use in Japan in 2010 [ 3 ]  and in Taiwan in 2018. [ 4 ]


Mederma  is a topical product used to improve  scar  appearance. It is a  gel  based on an  onion  extract. Mederma is product of HRA Pharma, a division of  Perrigo . A Mederma  marketing claim  is that the product can can make scars "softer, smoother, and less noticeable". [ 1 ]


The Mederma brand was owned by  Merz Pharma  for over 20 years until its 2019 sale to HRA Pharma. [ 2 ]  Perrigo then acquired HRA Pharma as a  subsidiary  in 2021. [ 3 ]


A 1999 pilot trial found an onion extract gel less effective than the petrolatum. [ 4 ]


A 2002 study published in  Plastic and Reconstructive Surgery  examined the effectiveness of Mederma on hypertrophic scars on rabbit ears. It found no significant reduction in the size, height, or inflammation of scars. The only improvement was dermal  collagen  organization when compared to scars that were not treated with Mederma, thus suggesting that it may have a positive effect on the formation of raised scars. [ 5 ]


A 2006  clinical trial  found no statistically significant change in  hypertrophic  scar appearance from products of this type compared to the standard petrolatum emollient. [ 6 ]


According to a 2011  Los Angeles Times  article, "there were just two randomized comparison trials of Mederma, with a combined total of 38 participants. Neither trial found that Mederma improved the appearance of scars more than petroleum jelly". [ 7 ]


Allantoin [ 8 ]


Water (purified), PEG 200, alcohol,  xanthan gum ,  allium cepa  (onion) bulb extract, lecithin,  methylparaben ,  sorbic acid , panthenol, sodium hyaluronate, fragrance [ 8 ]


PDC-APB , or  3-pentadecyl-1,2-phenylene bis(4-(4-aminophenyl)butanoate) , [ 1 ]  is a  drug candidate  under evaluation to determine if it might protect against  contact dermatitis  caused by  urishiol  from  poison ivy ,  poison oak , and  poison sumac . [ 2 ] [ 3 ] [ 4 ]


The compound is one of a class of compounds developed through  University of Mississippi  research [ 5 ]  by  Mahmoud ElSohly ,  Waseem Gul , and  Mohammad Khalid Ashfaq . [ 1 ]  Work on the compound is ongoing under  Hapten Sciences , [ 6 ]  who licensed the university's research in 2010. [ 5 ]


The compound has been evaluated in two  Phase I clinical trials , and a third Phase I  randomized controlled trial , with a secondary objective of evaluating the effect of treatment on urishiol sensitivity, is due to be completed in December 2022. [ 7 ] [ needs update ]


Pyrilutamide  (developmental code name  KX-826 ) is a  nonsteroidal antiandrogen  (NSAA) – specifically, a  selective  high- affinity   silent   antagonist  of the  androgen receptor  (AR) – which is under development by Suzhou Kintor Pharmaceuticals, inc., a subsidiary of Kintor Pharmaceutical Limited, for the potential treatment of  androgenic alopecia  (androgen-dependent scalp hair loss) [ 2 ] [ 3 ] [ 4 ]  As of September 2022, it is in  phase 3   clinical trials  for androgenic alopecia and  phase 2  trials for acne. [ 3 ]


Pyrilutamide has undergone several clinical trials for the treatment of androgenic alopecia (AGA) in both males and females. [ 5 ]  The primary endpoint for most trials was the change from baseline in non- vellus  target area hair count (TAHC) compared to placebo after 24 weeks of treatment. [ 5 ]


A phase II trial in China enrolled 120 male patients, randomized into four groups: KX-826 0.25% BID (twice daily), KX-826 0.5% QD (once daily), KX-826 0.5% BID, and placebo. After 24 weeks, the 0.5% BID group showed significant improvement: [ 5 ]


A phase II trial for female AGA in China included 160 patients in five groups: KX-826 0.25% QD, 0.25% BID, 0.5% QD, 0.5% BID, and placebo. After 24 weeks: [ 5 ]


A phase II trial in the U.S. enrolled 123 male patients, divided into KX-826 0.25% QD, 0.5% QD, 0.5% BID, and placebo groups. Results after 24 weeks showed: [ 5 ]


A phase III trial for male AGA in China enrolled 740 patients, randomized into KX-826 0.5% BID and placebo groups. Results announced on November 27, 2023, showed: [ 5 ]


In addition to its ongoing clinical development, Pyrilutamide has been introduced to the market as a cosmetic anti-hair loss product under the brand name Koshine. This approach allows it to be made available to consumers without the need for full regulatory approval as a medical treatment. Its classification as a cosmetic reflects a strategic decision to facilitate earlier access while formal medical approval is still pending. [ 6 ]


Pyrilutamide is generally well-tolerated. The most common adverse event is  contact dermatitis . [ 7 ]


Across all trials, KX-826 demonstrated a favorable safety profile: [ 5 ]


Pyrilutamide binds to the androgen receptor with a very high affinity with an  IC 50  of 0.28 nM. [ 4 ]  Reference drug  bicalutamide  had an IC 50  of 3.1 nM. [ 4 ]


A  rubefacient  is a substance for  topical  application that produces redness of the  skin , e.g. by causing  dilation  of the  capillaries  and an increase in  blood circulation . It has sometimes been used to relieve acute or chronic pain, but there is limited evidence as to its efficacy, [ 1 ] [ 2 ]  and as of 2014 the best evidence does not support using gels and creams containing rubefacients for this purpose. [ 1 ] [ better source needed ]


Common medicinal rubefacients include: [ 2 ]


Common herbal rubefacients include: [ citation needed ]


Sofpironium bromide , sold under the brand name  Ecclock  among others, is a  medication  used to treat  hyperhidrosis  (excessive sweating). [ 1 ]  Sofpironium bromide is an  anticholinergic  agent that is applied to the skin. [ 1 ]


It was approved in Japan in 2020, for the treatment of  primary axillary hyperhidrosis . [ 2 ]  It was approved for medical use in the United States in June 2024. [ 1 ] [ 3 ] [ 4 ]


Sofpironium bromide is  indicated  for the treatment of primary axillary hyperhidrosis. [ 1 ]


The pharmacodynamics of sofpironium bromide are unknown. [ 1 ]


It was approved for medical use in Japan in November 2020, [ 5 ]  and in the United States in June 2024. [ 1 ] [ 6 ]


Sofpironium bromide is the  international nonproprietary name . [ 7 ]


It is sold under the brand name Ecclock in Japan and under the brand name Sofdra in the US.


Tea tree oil , also known as  melaleuca oil , is an  essential oil  with a fresh,  camphoraceous   odour  and a colour that ranges from pale yellow to nearly colourless and clear. [ 1 ] [ 2 ]  It is derived from the  leaves  of the tea tree,  Melaleuca alternifolia , native to southeast  Queensland  and the northeast coast of  New South Wales , Australia. The oil comprises many constituent chemicals, and its composition changes if it is exposed to air and  oxidises . Commercial use of tea tree oil began in the 1920s, pioneered by the entrepreneur  Arthur Penfold .


There is little evidence for the effectiveness of tea tree oil in treating  mite-infected   crusting of eyelids , [ 3 ]  although some claims of efficacy exist. [ 4 ] [ 5 ]  In  traditional medicine , it may be applied  topically  in low concentrations for skin diseases, although there is little evidence for efficacy. [ 2 ] [ 6 ] [ 7 ] [ 8 ]


Tea tree oil is neither a  patented  product nor an  approved drug  in the United States, although it has been used in  skin care products [ 2 ] [ 8 ]  and is approved as a complementary medicine for  aromatherapy  in Australia. [ 9 ]  It is  poisonous  if consumed by mouth and is unsafe for children. [ 10 ]


Although tea tree oil is claimed to be useful for treating  dandruff ,  acne ,  lice ,  herpes ,  insect bites ,  scabies , and skin  fungal  or  bacterial  infections, [ 8 ] [ 11 ]  insufficient evidence exists to support any of these claims due to the limited quality of research. [ 2 ] [ 7 ] [ 12 ]  A 2015  Cochrane  review of acne complementary therapies found a single low-quality trial showing benefit on skin lesions compared to  placebo . [ 13 ]  Tea tree oil was also used during  World War II  to treat skin lesions of munitions factory workers. [ 2 ]


According to the  Committee on Herbal Medicinal Products  (CHMP) of the  European Medicines Agency , traditional usage suggests that tea tree oil is a possible treatment for "small, superficial wounds, insect bites, and small boils" and that it may reduce itching in minor cases of athlete's foot. The CHMP states that tea tree oil products should not be used on people under 12 years of age. [ 14 ]


Tea tree oil is not recommended for treating  nail fungus  because it is yet to be proven effective, [ 15 ]  It is not recommended for treating head lice in children because its effectiveness and safety have not been established and it could cause skin irritation or  allergic reactions . [ 16 ] [ 17 ]  As of 2020 [update] , there is uncertainty regarding the effectiveness of 5-50% tea tree oil as an effective treatment for  demodex  mite infestations, although products claiming efficacy exist. [ 18 ]


Tea tree oil is highly toxic when ingested orally. [ 2 ] [ 7 ] [ 19 ] [ 12 ]  It may cause drowsiness, confusion, hallucinations, coma, unsteadiness, weakness, vomiting, diarrhoea, nausea, blood-cell abnormalities, and severe rashes. It should be kept away from pets and children. [ 12 ]  It should not be used in or around the mouth. [ 2 ] [ 7 ] [ 10 ]


Application of tea tree oil to the skin can cause an allergic reaction in some, [ 2 ]  the potential for which increases as the oil ages and its chemical composition changes. [ 20 ]  Adverse effects include skin irritation, allergic contact dermatitis, systemic  contact dermatitis ,  linear immunoglobulin A disease ,  erythema multiforme -like reactions, and systemic  hypersensitivity  reactions. [ 11 ] [ 21 ]  Allergic reactions may be due to the various oxidation products that are formed by exposure of the oil to light and air. [ 21 ] [ 22 ]  Consequently, oxidised tea tree oil should not be used. [ 23 ]


In Australia, tea tree oil is one of the many  essential oils  causing poisoning, mostly of children. From 2014 to 2018, 749 cases were reported in New South Wales, accounting for 17% of essential oil poisoning incidents. [ 24 ]


Tea tree oil potentially poses a risk for causing  abnormal breast enlargement  in men [ 25 ] [ 26 ]  and prepubertal children. [ 27 ] [ 28 ]  A 2018 study by the  National Institute of Environmental Health Sciences  found four of the constituent chemicals ( eucalyptol ,  4-terpineol ,  dipentene , and  alpha-terpineol ) are  endocrine disruptors , raising concerns of potential  environmental health  impacts from the oil. [ 29 ]


In dogs and cats, death [ 30 ] [ 31 ]  or transient signs of toxicity (lasting two to three days), such as lethargy, weakness, incoordination, and muscle tremors, have been reported after external application at high doses. [ 32 ]


As a test of  toxicity  by oral intake, the  median lethal dose  (LD 50 ) in rats is 1.9–2.4 ml/kg. [ 33 ]


Tea tree oil is defined by the International Standard  ISO  4730 ("Oil of  Melaleuca ,  terpinen-4-ol  type"), containing terpinen-4-ol, γ- terpinene , and α-terpinene as about 70% to 90% of whole oil, while  p -cymene , terpinolene, α-terpineol, and  α-pinene  collectively account for some 15% of the oil (table). [ 1 ] [ 6 ] [ 8 ]  The oil has been described as colourless to pale yellow [ 1 ] [ 2 ]  having a fresh,  camphor -like smell. [ 34 ]


Tea tree oil products contain various  phytochemicals , among which  terpinen-4-ol  is the major component. [ 1 ] [ 2 ] [ 6 ]  Adverse reactions diminish with lower  eucalyptol  content. [ 11 ]


The name "tea tree" is used for several plants, mostly from  Australia  and  New Zealand , from the family  Myrtaceae  related to the  myrtle . The use of the name probably originated from  Captain James Cook 's description of one of these shrubs that he used to make an  infusion  to drink in place of  tea . [ 35 ]


The commercial tea tree oil industry originated in the 1920s when Australian chemist  Arthur Penfold  investigated the business potential of a number of native extracted oils; he reported that tea tree oil had promise, as it exhibited  antiseptic  properties. [ 33 ]


Tea tree oil was first  extracted  from  Melaleuca alternifolia  in Australia, and this species remains the most important commercially. In the 1970s and 1980s, commercial plantations began to produce large quantities of tea tree oil from  M. alternifolia . Many of these plantations are located in New South Wales. [ 33 ]  Since the 1970s and 80s, the industry has expanded to include several other species for their extracted oil:  Melaleuca armillaris  and  Melaleuca styphelioides  in Tunisia and Egypt;  Melaleuca leucadendra  in Egypt, Malaysia, and Vietnam;  Melaleuca acuminata  in Tunisia;  Melaleuca ericifolia  in Egypt; and  Melaleuca quinquenervia  in the United States (considered an invasive species in Florida [ 36 ] ).


Similar oils can also be produced by water distillation from  Melaleuca linariifolia  and  Melaleuca dissitiflora . [ 37 ]  Whereas the availability and  nonproprietary  nature of tea tree oil would make it – if proved effective – particularly well-suited to a disease such as scabies that affects poor people disproportionately, those same characteristics diminish corporate interest in its development and validation. [ 8 ]


Tralokinumab  sold under the brand names  Adtralza  (EU/UK) and  Adbry  (US) among others, is a  human monoclonal antibody  used for the treatment of  atopic dermatitis . [ 3 ] [ 5 ]  Tralokinumab targets the cytokine  interleukin 13 . [ 8 ]


The most common side effects include upper respiratory tract infections (colds and other infections of the nose and throat), reactions at the injection site, and redness and discomfort in the eye. [ 5 ]


Tralokinumab was approved for medical use in the European Union and in the United Kingdom in June 2021. [ 3 ] [ 5 ] [ 9 ]  It was approved for medical use in the United States in December 2021. [ 7 ] [ 10 ] [ 4 ]  The U.S.  Food and Drug Administration  (FDA) considers it to be a  first-in-class medication . [ 11 ]


Tralokinumab is  indicated  for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. [ 5 ] [ 3 ]


In the United States, tralokinumab is indicated for the treatment of moderate-to-severe atopic dermatitis in adults whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. [ 4 ] [ 7 ]


Tralokinumab was discovered by  Cambridge Antibody Technology  scientists [ 12 ] [ 13 ] [ 14 ]  using protein optimization based on  Ribosome Display . [ 15 ]  They used the extensive data sets from ribosome display to patent protect CAT-354 in a world-first of sequence-activity-relationship claims. [ 14 ]  In 2004, clinical development of CAT-354 was initiated with this first study completing in 2005. [ 16 ]  On 21 July 2011,  MedImmune  LLC initiated a Phase IIb, randomized, double-blind study to evaluate the efficacy of tralokinumab in adults with asthma. [ 17 ] [ 18 ] [ 19 ]


In 2016, MedImmune and AstraZeneca started developing tralokinumab for asthma (Phase III) and atopic dermatitis (Phase IIb) while clinical development for moderate-to-severe  ulcerative colitis  and idiopathic pulmonary fibrosis (IPF) have been discontinued. [ 16 ]  In July of that year AstraZeneca licensed tralokinumab to  Leo Pharma  for skin diseases. [ 20 ]


A phase IIb study of tralokinumab found that treatment was associated with early and sustained improvements in atopic dermatitis symptoms and tralokinumab had an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with atopic dermatitis. [ 21 ]


In June 2017,  Leo Pharma  started phase III clinical trials with tralokinumab in atopic dermatitis. [ 22 ]


In April 2021, the  Committee for Medicinal Products for Human Use  of the  European Medicines Agency  adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Adtralza, intended for the treatment of moderate‑to‑severe atopic dermatitis. [ 23 ]  The applicant for this medicinal product is LEO Pharma A/S. [ 23 ]  Tralokinumab was approved for medical use in the European Union in June 2021. [ 5 ]


Tralokinumab is the  international nonproprietary name  (INN) [ 24 ]  and the  United States Adopted Name  (USAN). [ 25 ]


Immune activation :  Dostarlimab
 Other:   Ibalizumab


Urea , also known as  carbamide-containing cream , [ clarification needed ]  is used as a medication and applied to the skin to treat dryness and itching such as may occur in  psoriasis ,  dermatitis , or  ichthyosis . [ 1 ] [ 2 ] [ 3 ]  It may also be used to soften  nails . [ 3 ]


In adults side  effects are generally few. [ 4 ]  It may occasionally cause skin irritation. [ 1 ]  Urea works in part by loosening dried skin. [ 5 ]  Preparations generally contain 5 to 50%  urea . [ 2 ] [ 3 ]


Urea  containing creams have been used since the 1940s. [ 6 ]  It is on the  World Health Organization's List of Essential Medicines . [ 7 ]  It is available  over the counter . [ 3 ]


Urea cream is indicated for  debridement  and promotion of normal healing of skin areas with  hyperkeratosis , particularly where healing is inhibited by local  skin infection , skin  necrosis , fibrinous or itching debris or  eschar . [ 5 ]  Specific condition with hyperkeratosis where urea cream is useful include:


Common side effects of urea cream are:


In severe cases, there can be an  allergic reaction  with symptoms such as  skin rash ,  urticaria ,  difficulty breathing  and swelling of the mouth, face, lips, or tongue. [ 8 ]


Urea in low doses is a  humectant  while at high doses (above 20%) it causes breakdown of protein in the skin. [ 9 ]


Urea dissolves the  intercellular matrix  of the cells of the  stratum corneum , promoting  desquamation  of  scaly skin , eventually resulting in softening of  hyperkeratotic  areas. [ 5 ]  In  nails , urea causes softening and eventually debridement of the nail plate. [ 5 ]


Dermatology  is the branch of  medicine  dealing with the  skin . [ 1 ] [ 2 ]  It is a speciality with both medical and surgical aspects. [ 3 ] [ 4 ] [ 5 ]  A  dermatologist  is a specialist medical doctor who manages diseases related to skin, hair, nails, and some cosmetic problems. [ 2 ] [ 6 ]


Attested in English in 1819, the word "dermatology" derives from the  Greek  δέρματος ( dermatos ), genitive of δέρμα ( derma ), "skin" [ 7 ]  (itself from δέρω  dero , "to flay" [ 8 ] ) and -λογία  -logia . Neo-Latin  dermatologia  was coined in 1630, an anatomical term with various French and German uses attested from the 1730s. [ 9 ]


In 1708, the first great school of dermatology became a reality at the famous  Hôpital Saint-Louis  in Paris, and the first textbooks (Willan's, 1798–1808) and atlases ( Alibert's , 1806–1816) appeared in print around the same time. [ 10 ]


After earning a medical degree ( M.D.  or  D.O. ), the length of training in the United States for a general dermatologist to be eligible for board certification by the  American Academy of Dermatology ,  American Board of Dermatology , or  American Osteopathic Board of Dermatology  is four years. [ 11 ]  This training consists of an initial medical, transitional, surgical, or pediatric intern year followed by a three-year dermatology residency. [ 2 ] [ 12 ] [ 13 ]  Following this training, one- or two-year post-residency fellowships are available in  immunodermatology ,  phototherapy ,  laser medicine ,  Mohs micrographic surgery ,  cosmetic surgery ,  dermatopathology , or pediatric dermatology. While these dermatology fellowships offer additional subspecialty training, many dermatologists proficiently provide these services without subspecialty fellowship training. For the past several years, dermatology residency positions in the United States have been one of the most competitive to obtain. [ 14 ] [ 15 ] [ 16 ]


According to the American Academy of Dermatology, dermatologists are trained to diagnose and manage over 3,000 distinct skin, hair, and nail conditions across patients spanning various age groups. [ 17 ]


The United States has been experiencing a national shortage of dermatologists for more than a decade. A study published by the  Journal of the American Medical Association  reported fewer than 3.4 dermatologists for every 100,000 people. [ 18 ]


In the UK, a dermatologist is a medically qualified practitioner who has gone on to specialize in medicine and then subspecialize in dermatology. This involves:


Upon successful completion of the four-year training period, the doctor becomes an accredited dermatologist and is able to apply for a consultant hospital post as a consultant dermatologist. [ 19 ]


Dermatologists have been leaders in the field of cosmetic surgery. [ 20 ]  Some dermatologists complete fellowships in surgical dermatology. Many are trained in their residency on the use of  botulinum toxin , fillers, and laser surgery. Some dermatologists perform cosmetic procedures including  liposuction ,  blepharoplasty , and  face lifts . [ 21 ] [ 22 ]  Most dermatologists limit their cosmetic practice to minimally invasive procedures. Despite an absence of formal guidelines from the  American Board of Dermatology , many cosmetic fellowships are offered in both surgery and laser medicine. [ 23 ]


A dermatopathologist is a  pathologist  or dermatologist who specializes in the  pathology  of the skin. [ 24 ]  This field is shared by dermatologists and pathologists. Usually, a dermatologist or pathologist completes one year of dermatopathology fellowship and according to market projections, it is estimated to expand at a compound annual growth rate (CAGR) of 11.4% from 2022 to 2030. This usually includes six months of general pathology and six months of dermatopathology. [ 25 ]  Alumni of both specialties can qualify as dermatopathologists. At the completion of a standard residency in dermatology, many dermatologists are also competent at dermatopathology. Some dermatopathologists qualify to sit for their examinations by completing a residency in dermatology and one in pathology. [ citation needed ]


Trichology specializes in diseases, which manifest with hair loss, hair abnormalities,  hypertrichosis  and scalp changes.  Trichoscopy  is a medical diagnostic method that is used by dermatologists with a special interest in trichology. [ 26 ]


This field specializes in the treatment of immune-mediated skin diseases such as  lupus ,  bullous pemphigoid ,  pemphigus vulgaris , and other immune-mediated skin disorders. [ 27 ]  Specialists in this field often run their own immunopathology labs. [ citation needed ]  Immunodermatology testing is essential for the correct diagnosis and treatment of many diseases affecting epithelial organs including skin, mucous membranes, gastrointestinal and respiratory tracts. The various diseases often overlap in clinical and histological presentation and, although the diseases themselves are not common, may present with features of common skin disorders such as urticaria, eczema and chronic itch. Therefore, the diagnosis of an immunodermatological disease is often delayed. Tests are performed on blood and tissues that are sent to various laboratories from medical facilities and referring physicians across the United States. [ 28 ]


The dermatologic subspecialty called Mohs surgery focuses on the excision of skin cancers using a technique that allows intraoperative assessment of most of the peripheral and deep tumor margins. Developed in the 1930s by  Frederic E. Mohs , the procedure is defined as a type of  CCPDMA  processing. Physicians trained in this technique must be comfortable with both pathology and surgery, and dermatologists receive extensive training in both during their residency. Physicians who perform Mohs surgery can receive training in this specialized technique during their dermatology residency, but many seek additional training either through formal preceptorships to become fellows of the American Society for Mohs Surgery [ 29 ]  or through one-year Mohs surgery fellowship training programs administered by the American College of Mohs Surgery. [ 30 ]  In 2020, the American Board of Dermatology (ABD) received approval from the American Board of Medical Specialties (ABMS) to establish a board-certification exam in the subspecialty of Micrographic Dermatologic Surgery (Mohs Surgery). The exam was first offered in October 2021 to any US board-certified dermatologist who practices Mohs surgery, regardless of whether they received their training in dermatology residency or as part of a fellowship. [ 31 ]


This technique requires the integration of the same doctor in two different capacities - surgeon and pathologist. In case either of the two responsibilities is assigned to another doctor or qualified health-care professional, it is not considered to be Mohs surgery. [ citation needed ]


Physicians can qualify for this specialization by completing both a pediatric residency and a dermatology residency. Or they might elect to complete a post-residency fellowship. [ 32 ]  This field encompasses the complex diseases of the  neonates , hereditary skin diseases or  genodermatoses , and the many difficulties of working with the  pediatric  population. [ 33 ]  Another area pediatric dermatologists may focus on is treating acne. Acne is formed when follicles under the skin become clogged. This can be caused by sebum, an oil that keeps the skin moist, or dead skin cells clogging the pores. This is very common in teens and young adults, and can be treated by prescription from a dermatologist.  [ 34 ]


Teledermatology is a form of dermatological practice in which telecommunication technologies are used to exchange medical information and treatment through audio, visual, and data communication, including photos of dermatologic conditions, between dermatologists and nondermatologists who are evaluating patients, along with dermatologists directly with patients via distance. [ 35 ] [ 36 ] [ 37 ]  In India, during the severe coronavirus situations, some dermatologists have initiated online consultation with their patients using some of popular apps, such as Practo, Apollo Pharmacy, Skin Beauty Pal, Lybrate, etc. This subspecialty deals with options to view skin conditions over a large distance to provide  knowledge exchange , [ 38 ]  to establish second-opinion services for experts, [ 39 ]  or to use this for follow-up of individuals with chronic skin conditions. [ 40 ] [ 41 ]  Teledermatology can reduce wait times by allowing dermatologists to treat minor conditions online while serious conditions requiring immediate care are given priority for appointments. [ 42 ]


Dermatoepidemiology is the study of skin disease at the population level. [ 43 ]  One of its aspects is the determination of the global burden of skin diseases. [ 44 ] [ 45 ]
From 1990 to 2013, skin disease constituted about 2% of total global disease disability  [ 46 ]  as measured in disability-adjusted life-years. [ 47 ]


Comparative dermatology is a branch of dermatology that examines skin disorders across species, focusing on similarities and differences between humans and animals, such as dogs. This interdisciplinary approach is crucial for enhancing our understanding of dermatological conditions and developing more effective treatment and prevention strategies.


Skin disorders are common in dogs, significantly affecting their quality of life and often requiring veterinary intervention. While some breeds are genetically predisposed to specific skin issues, there remains a notable gap in research comparing these canine conditions to similar human skin disorders. Addressing this gap can yield insights into the shared mechanisms underlying these diseases. For instance, atopic dermatitis. [ 48 ]  It is a common, itchy, and often difficult-to-treat condition. The Merck Veterinary Manual highlights various congenital and inherited skin disorders in dogs that are influenced by these factors, emphasizing the need for comparative research to improve disease management across species. [ 49 ]  By comparing the disease in animals and humans, researchers can gain insights into its progression and variability in response to treatments.


Furthermore, research into the genetic underpinnings of skin disorders has demonstrated that certain genetic mutations in dogs are associated with inherited skin diseases, which may serve as models for understanding similar human conditions. [ 50 ]  Environmental factors, such as allergens and pollutants, also play a significant role in skin health. Studies published in journals focusing on inflammatory skin conditions in humans and veterinary research reveal how these environmental influences intersect with genetic predispositions, offering a comparative framework for further study. [ 51 ]


Treatment strategies for skin disorders also differ between veterinary and human medicine. Veterinary treatments often prioritize symptomatic relief and prevention, while human dermatological care may involve a broader range of targeted pharmaceutical options. Comparative analysis of these treatment methodologies could lead to the development of new therapies beneficial to both fields, as discussed in microbiological research into skin health. [ 52 ]


By emphasizing the comparative aspects of dermatology, researchers can contribute to a deeper understanding of skin health across species. This field underscores the importance of genetic research, environmental studies, and treatment innovations, as evidenced by ongoing research in dermatological and veterinary science.


Therapies provided by dermatologists include:


Most dermatologic pharmacology can be categorized based on the  Anatomical Therapeutic Chemical (ATC) classification system , specifically the  ATC code D .


Acres of Skin: Human Experiments at Holmesburg Prison  is a 1998 book by  Allen Hornblum . The book documents clinical non-therapeutic  medical experiments on prison inmates  at  Holmesburg Prison  in Philadelphia from 1951 to 1974, conducted under the direction of  dermatologist   Albert Kligman . [ 1 ]  The title of the book is a reference to Kligman's reaction on seeing hundreds of prisoners when he entered the prison: "All I saw before me were acres of skin"; "It was like a farmer seeing a fertile field for the first time". [ 2 ]


The book discusses issues surrounding the inadequate consent procedures of the 1950s and 1960s when using prisoners.  Prisoners, attracted by the compensation, were angry when two of the experiment's participants testified before Congress. [ 3 ]


The publication of  Acres of Skin  in 1998 attracted considerable international media interest. [ 2 ]  The book has been reviewed in several journals including the  International Journal of Dermatology , [ 4 ]   Social History of Medicine [ 5 ]  and  Canadian Journal of History . [ 1 ] [ 6 ] [ 7 ] [ 8 ]


Actinic keratosis  ( AK ), sometimes called  solar keratosis  or  senile keratosis , [ 1 ] [ 2 ]  is a  pre-cancerous [ 3 ]  area of thick, scaly, or crusty skin. [ 4 ] [ 5 ]  Actinic keratosis is a disorder ( -osis ) of  epidermal   keratinocytes  that is induced by  ultraviolet (UV)  light exposure ( actin- ). [ 6 ]


These growths are more common in  fair-skinned  people and those who are frequently in the  sun . [ 7 ]  They are believed to form when  skin  gets damaged by UV radiation from the sun or indoor  tanning beds , usually over the course of decades. Given their pre-cancerous nature, if left untreated, they may turn into a type of skin cancer called  squamous cell carcinoma . [ 5 ]  Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, [ 8 ]  so treatment by a  dermatologist  is recommended.


Actinic keratoses characteristically appear as thick, scaly, or crusty areas that often feel dry or rough. Size commonly ranges between 2 and 6  millimeters , but they can grow to be several centimeters in diameter.  AKs are often felt before they are seen, and the texture is sometimes compared to  sandpaper . [ 9 ]  They may be dark, light, tan, pink, red, a combination of all these, or have the same color as the surrounding skin.


Given the causal relationship between sun exposure and AK growth, they often appear on a background of sun-damaged skin and in areas that are commonly sun-exposed, such as the face, ears, neck, scalp, chest, backs of hands, forearms, or lips.  Because sun exposure is rarely limited to a small area, most people who have an AK have more than one. [ 10 ]


If clinical examination findings are not typical of AK and the possibility of in situ or invasive  squamous cell carcinoma (SCC)  cannot be excluded based on clinical examination alone, a  biopsy  or  excision  can be considered for definitive diagnosis by  histologic  examination of the lesional tissue. [ 11 ]  Multiple treatment options for AK are available.  Photodynamic therapy  (PDT) is one option for the treatment of numerous AK lesions in a region of the skin, termed field cancerization. [ 12 ]  It involves the application of a photosensitizer to the skin followed by illumination with a strong light source. Topical creams, such as  5-fluorouracil  or  imiquimod , may require daily application to affected skin areas over a typical time course of weeks. [ 13 ]


Cryotherapy  is frequently used for few and well-defined lesions, [ 14 ]  but undesired skin lightening, or hypopigmentation, may occur at the treatment site. [ 15 ]  By following up with a dermatologist, AKs can be treated before they progress to skin cancer. If cancer does develop from an AK lesion, it can be caught early with close monitoring, at a time when treatment is likely to have a high cure rate.


Actinic keratoses (AKs) most commonly present as a white, scaly  plaque  of variable thickness with surrounding redness; they have a sandpaper-like texture when felt with a gloved hand. Skin nearby the lesion often shows evidence of solar damage characterized by pigmentary alterations, being yellow or pale in color with areas of hyperpigmentation; deep wrinkles, coarse texture,  purpura  and  ecchymoses ,  dry skin , and scattered  telangiectasias  are also characteristic. [ 16 ]


Photoaging leads to an accumulation of  oncogenic  changes, resulting in a proliferation of mutated  keratinocytes  that can manifest as AKs or other neoplastic growths. [ 17 ]  With years of sun damage, it is possible to develop multiple AKs in a single area on the skin.  This condition is termed field cancerization.


The lesions are usually asymptomatic, but can be tender, itch, bleed, or produce a stinging or burning sensation. [ 18 ]  AKs are typically graded in accordance with their clinical presentation: Grade I (easily visible, slightly palpable), Grade II (easily visible, palpable), and Grade III (frankly visible and hyperkeratotic). [ 19 ]


Actinic keratoses can have various clinical presentations, often characterized as follows:


The presence of  ulceration ,  nodularity , or  bleeding  should raise concern for malignancy. [ 23 ]  Specifically, clinical findings suggesting an increased risk of progression to  squamous cell carcinoma  can be recognized as "IDRBEU": I (induration/inflammation), D (diameter > 1 cm), R (rapid enlargement), B (bleeding), E (erythema), and U (ulceration). [ 24 ]  AKs are usually diagnosed clinically, but because they are difficult to clinically differentiate from squamous cell carcinoma, any concerning features warrant biopsy for diagnostic confirmation. [ 25 ]


The most important cause of AK formation is solar radiation, through a variety of mechanisms.  Mutation of the  p53  tumor suppressor gene, induced by UV radiation, has been identified as a crucial step in AK formation. [ 26 ]  This  tumor suppressor gene , located on  chromosome 17p 132, allows for  cell cycle  arrest when DNA or RNA is damaged.  Dysregulation  of the p53 pathway can thus result in unchecked replication of dysplastic keratinocytes, thereby serving as a source of  neoplastic  growth and the development of AK, as well as possible progression from AK to skin cancer. [ 27 ]  Other  molecular markers  that have been associated with the development of AK include the expression of p16 ink4 , p14, the  CD95  ligand,  TNF -related apoptosis-inducing ligand ( TRAIL ) and TRAIL receptors, and  loss of heterozygosity . [ 28 ] [ 27 ]


Evidence also suggests that the  human papillomavirus  (HPV) plays a role in the development of AKs. The HPV virus has been detected in AKs, with measurable HPV viral loads (one HPV-DNA copy per less than 50 cells) measured in 40% of AKs. [ 29 ]  Similar to UV radiation, higher levels of HPV found in AKs reflect enhanced viral DNA replication.  This is suspected to be related to the abnormal keratinocyte proliferation and differentiation in AKs, which facilitate an environment for HPV replication. This in turn may further stimulate the abnormal proliferation that contributes to the development of AKs and carcinogenesis.