Allantoin is a natural compound concentrated in comfrey root that promotes wound healing speeds up cell regeneration and has a skin-softening (keratolytic) effect. The Merck Index lists the therapeutic applications of allantoin as a topical vulnerary (wound healer) and treatment for skin ulcers. The FDA has approved allantoin skin creams (0.5% to 2.0%) as non-prescription drug products for: 1) the temporary protection of minor cuts scrapes burns and sunburn; 2) preventing and protecting skin and lips against chapping chafing cracking and wind-burn and 3) relieving dryness and softening cold sores and fever blisters.
Allantoin is also recommended for treating and preventing diaper rash and additionally helps to seal out wetness. Allantoin is also used in shampoos foam baths baby powders lipsticks various dental preparations and topical pharmaceuticals. The FDA OTC (over-the-counter Drug) Panel does not recognize allantoin as a wound-healing agent only as a skin protectant. However allantoin is ter ed as a cell proliferant and epithelization (skin growth) stimulant in texts including the 'United States Dispensatory' 'Merck Index' and 'British Pharmaceutical Codex'. Allantoin is said to clean away dead (necrotic) tissue and hasten the growth of new healthy tissue. Since allantoin stimulates new and healthy tissue growth skin formation may take place over wounds and sores. Allantoin has also been termed a counter irritant that helps alleviate the skin-irritation effects of certain cosmetic ingredients including soaps detergents surfactants oils and acidic or alkaline materials. Allantoin produces its desirable effects by promoting and speeding up the healthy natural processes of the body. It is said to help the skin to help itself. Allantoin is the soothing and healing constituent in comfrey root valued for use in creams and lotions for these properties. Comfrey teas containing allantoin are also recommended for speeding the healing of bruises sprains bone fractures and broken bones.
Allantoin is a botanical extract of the comfrey plant and is used for its healing soothing and anti-irritating properties. Allantoin helps to heal wounds and skin irritations and stimulate growth of healthy tissue. This extract can be found in anti-acne products sun care products and clarifying lotions because of its ability to help heal minor wounds and promote healthy skin.
Its chemical formula is C4H6N4O3. It is also called 5-ureidohydantoin glyoxyldiureide and 5-ureidohydantoin. It is a product of oxidation of uric acid. It is a diureide of glyoxilic acid. It is a product of purine metabolism in most mammals except higher apes and it is present in their urine.
The keratolytic effect and abrasive and adstringent properties of allantoin are used in skin softening cosmetic preparations. It is also frequently present in toothpaste mouthwash and other oral hygiene products in shampoos lipsticks various cosmetic lotions and creams and other cosmetic and pharmaceutical products.
Allantoin in its pure form is a white odourless crystalline powder soluble in water and alcohol and almost insoluble in ether. The Merck Index describes allantoin as a product of purine metabolism that is industrially prepared synthetically by a process using uric acid. It is nontoxic nonirritating and non-allergenic. Chemical name: glyoxyl-diureide. Molecular weight: 158.12. Melting range: 225C Heavy metals: 10 ppm maximum. Solubility in water: 0.5% at 25C. Can dissolve in hot water hot mellow watery sodium hydroxide solution dissolve in the water and mellow with normal temperature slightly hardly dissolve in the organic solvents such as aether and chloroform. Its saturated watery solution ( concentration is 0.6 % ) presents the slight acidity . PH value is 5.5 stable in the watery solution with PH value 4—9 also stable in non-watery solvents and dry air can be seethed in strong alkali solution and decompose by exposing to the sunlight .
5-Ureidohydantoin; Glyoxyldiureide; Alantan; Alloxantin;
Ureidohydantoin; Hemocane; Paxyl; Allantol; Cordianine; Glyoxyldiureid; Hydantoin 5-ureido-; 25-Dioxo-4-imidazolidinyl-urea;
DESCRIPTION: When isolated Allantoin is a white odorless crystalline powder.
INCI ADOPTED NAME:
Category I (Safe and Effective) OTC Tentative Final Monograph on Skin Protectant Drugs
Use rate of allantoin is 0.5 - 2.0% w/w. Small concentrations can be added to the water phase to incorporate more than 0.5% into an emulsion add during the cooling phase once the temperature has dropped below 50°C/122°F.
Simultaneous Measurement of Allantoin and Urate in Plasma: Analytical Evaluation and Potential Clinical Application in Oxidant:Antioxidant Balance Studies:
In humans allantoin is formed by nonenzymatic oxidation of urate; it may therefore be useful in assessing oxidative stress. Most published methods involve separate analysis of urate and allantoin and require extraction hydrolysis and derivatization procedures . The primary aim of this study was to evaluate a slightly modified version of an HPLC assay described by Lux et al. for the simultaneous measurement of urate and allantoin. A secondary aim was to explore the clinical utility of allantoin as a biomarker of oxidative stress the hypothesis being that in disease associated with increased oxidative stress allantoin increases because of an increased 'oxidative turnover' of urate. The final aim of the study was to investigate the effect of age on urate and allantoin concentrations.
Allantoin and uric acid were from Sigma; 1-heptanesulfonic acid sodium salt monohydrate was from Sigma-Aldrich; potassium dihydrogen phosphate was from Merck; sodium hydroxide was from Riedel-de Haen; orthophosphoric acid was from BDH and Moni-Trol Level 1 Chemistry Control Serum was from Dade International. MilliQ water (Millipore ultra-pure water system; Millipore) was used for preparation of all solutions. Aqueous stock solutions of allantoin (1000 µmol/L) and urate (2000 µmol/L) were prepared and stored at 4 °C. Because uric acid (urate) is more soluble at alkaline pH sodium hydroxide (1 mol/L) was added dropwise until the pH was ~9.0; at this pH all urate was dissolved. Calibrators (10–100 µmol/L for allantoin; 50–1000 µmol/L for urate) were prepared in mobile phase from stock solutions: 25 µL of each calibrator was mixed with 25 µL of Moni-Trol control serum and 75 µL of mobile phase. Ultrafiltrates (see below) of diluted calibrators were used to construct daily calibration curves. For precision studies we used 1-mL aliquots of pooled heparinized plasma with or without added allantoin (25 µL of stock solution) and urate (250 µL of stock solution) to prepare control samples. For sample preparation we vortex-mixed 25.0 µL of sample or control with 100 µL of mobile phase transferred the mixture into a filter unit (Millipore Ultrafree-MC 30 000 NMWL polysulfone-membrane filter unit; Millipore) that had been prewashed twice before use with 300 µL of water to remove the humectant (glycerol) and centrifuged the mixture in a MSE Micro Centaur (MSE Scientific Instruments) at 2500g for 10 min to remove protein and other molecules of Mr >30 000. Ultrafiltrate (20 µL) was injected into the HPLC system which comprised an isocratic pump (ISCO model 2350 pump with a 20-µL looped Valco manual injector; ISCO) a variable wavelength absorbance detector (ISCO model V4 detector with 5-mm flow cell path) a cartridge guard column (Spherisorb C18 5 µm 10 x 4.6 mm i.d. cartridge; ISCO) and a reversed-phase analytical column (ISCO C18 5 µm 250 x 4.6 mm i.d.). The mobile phase was aqueous 5 mmol/L potassium dihydrogen phosphate containing 5 mmol/L 1-heptanesulfonic acid (ion-pairing reagent) and adjusted to pH 3.1 using orthophosphoric acid. The flow rate was 1.0 mL/min and detection was at 210 nm.
Because urate reportedly is less stable at alkaline pH (2) the stability of the stock urate calibrator (pH 9.4) was assessed. To check whether membrane filtration caused loss of analyte fresh fasting heparinized plasma was analyzed with and without filtration. Linearity was assessed by repeated measurements of Moni-Trol control at various concentrations. Recovery was assessed by the addition of allantoin (25 µmol/L) and urate (250 µmol/L) to pooled plasma. A signal-to-noise ratio of 3:1 was used to determine detection limits.
This study was approved by the Ethics Subcommittee of the Hong Kong Polytechnic University and all procedures involving human subjects complied with the Declaration of Helsinki as revised in 1996.
The method showed clear separation of allantoin and urate with retention times of 3.0 and 9.5 min respectively (Fig. 1 ). The detection limit for allantoin and urate in mobile phase was 20 pmol (equivalent to a plasma concentration of 5 µmol/L). The within- (n = 9) and between-day (n = 6) CVs for allantoin (15–25 µmol/L) were <4% and <7% respectively; the within- and between-day CVs for urate (50–500 µmol/L) were <4%. The calibration curves were linear to 100 µmol/L for allantoin and 1000 µmol/L for urate. Recovery (n = 6) was 92% for allantoin and 98% for urate. Aqueous allantoin and urate (pH 9.4) stock calibrators were stable at 4 °C for at least 7 and 2 weeks respectively.
Figure 1. Typical chromatograms of allantoin and urate. (A) pure calibrators (allantoin prepared in water and urate in dilute sodium hydroxide solution) were diluted and mixed in mobile phase. The final mixture was injected directly into the HPLC system without ultrafiltration. (B) fasting heparinized plasma from one healthy subject after ultrafiltration.
Table 1. Allantoin and urate concentrations in biological fluids as reported in current and previous studies.
Allantoin µmol/L: range and/or mean (SD)
Urate µmol/L: range and/or mean (SD)
Allantoin:urate ratio %: range and/or mean (SD)
40; 23 males 17 females
14.8–27.8; 20.8 (3.8) males 21.0 (2.0) females
241–477; 380 (59) males 290 (41) females
5.55 (1.11) males 7.37 (1.26) females
64; 27 males 37 females
14.5–48.2; 23.7 (6.6) males 23.0 (6.0) females
135–635; 366 (98) males 352 (112) females
6.77 (2.06) males 6.87 (1.73) females
7; 4 males 3 females
14.1–25.4; 18.6 (3.8) all
258–621; 432 (121) all
4.7 (1.6) all
Grootveld and Halliwell (2)
9; 1 male 8 females
7.2–31.3; 29.9 (7.3) all
123–351; 205 (92) all
11.8 (5.6) all
Grootveld and Halliwell (2)
4; 2 males 2 females
20.3–45.2; 36.1 (6.3) all
273–485; 375 (102) all
10.5 (3.8) all
Grootveld and Halliwell (2)
Lagendijk et al. (3)
18 (no M/F information)
Lux et al. (7)
Hellsten et al. (5)
206 (55) males 320 (55) females
Kock et al. (6)
15; 9 males 6 females
240–450; 370 (80) all
Naidoo and Lux (9)
The U.S. Food and Drug Administration (FDA) has classified Allantoin as a Category I (safe and effective) active ingredient skin protectant.
The FDA's Tentative Final Monograph on skin protectant drug products for Over-The-Counter (OTC) human use was published in the Federal Register (Volume 48 No. 32 pp. 6820-33 and Volume 55 No. 11 pp. 25240-81). Based on the wide use and clinical acceptance of Allantoin as well as published reports in the literature the FDA has approved the following statements for non-prescription drug products containing Allantoin at 0.5% to 2.0%.
1. For the temporary protection of minor cuts scrapes burns and sunburn.
2. Helps prevent and temporarily protects chafed chapped cracked or wind-burned skin and lips.
3. Relieves dryness and softens cold sores and fever blisters.
4. Helps treat and prevent diaper rash. Protects chafed skin/minor skin irritation due to/associated with diaper rash and helps protect from/seal out wetness.
Allantoin is considered to be nontoxic nonirritating and non-allergenic by the Schwartz patch test on 200 individuals as published in the Federal Register (Volume 43 No. 151 pp. 34632-34). Clinical and marketing experience has confirmed that Allantoin is safe and effective in the dosage range recommended (0.5 to 2.0%) as a skin protectant.
Allantoin is a kind of important fine chemical with a broad purpose universally used in pharmaceuticals light industry agriculture daily chemicals and biology engineering.
Allantoin has many physiologies such as accelerating the growth of the cells expediting the wound to cicatrize intenerating horn albumen etc and it is also a good cicatrisation and anti-canker dosage for the skin wound which can be used to relax and cure skin xerosis dry scaly skin bits skin canker alimentary canal canker and inflammation and have a preferable curative effects on the osteomyelitis diabetes hepatocirrhosis and acne.