encyclopedia

Allantoin (Supplement)

Natural Sources:    

Comfrey root (Symphytum officinale L.), egg whites, and other foods.    
     
Forms:    

Standardized allantoin extracts; allantoin creams; comfrey root extracts.    
     
Therapeutic Uses:     

– Antibacterial (topically)
– Bone and Joint Conditions
– Bruises
– Burns
– Compress
– Diaper Rash
– Fractures
– Inflammation
– Joint Dislocations
– Psoriasis
– Scar Healing
– Skin Healing
– Skin Problems
– Skin Roughness
– Skin Softening
– Skin Ulcers
– Sprains
– Swelling (topically)
– Tissue Damage
– Ulcers (externally)
– Wound Healing     
             
     
Overview:    

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.
    
             
     
Chemistry:    

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.    
             
     
Suggested Amount:    

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.    
             
     
Drug Interactions:    

None known.    
             
     
Contraindications:    

None known.    
             
     
Side Effects:    

Cetyl alcohol used in skin cream formulations generally does not produce any side effects. However, cetyl alcohol may cause skin irritation in sensitive persons.    
             
     
References:     
     
Cajkovac M, Oremovic L, Cajkovac V. 1991. Influence of emulsoid vehicle on the release and activity of allantoin. Pharmazie 1992 Jan; 47(1): 39-43.
 
Fisher AA. 1981. Allantoin: a non-sensitizing topical medicament. Therapeutic effects of the addition of 5 percent allantoin to Vaseline. Cutis. 1981 Mar; 27(3): 230-1, 234, 329.
 
Pinheiro N. 1997. Comparative effects of calcipotriol ointment (50 micrograms/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream in treating plaque psoriasis. Br J Clin Pract 1997 Jan-Feb; 51(1): 16-9.
 
Sakuma K, Ogawa M, Kimura M, Yamamoto K, Ogihara M. 1998. [Inhibitory effects of shimotsu-to, a traditional Chinese herbal prescription, on ultraviolet radiation-induced cell damage and prostaglandin E2 release in cultured Swiss 3T3 cells]. Yakugaku Zasshi 1998 Jun; 118(6): 241-7. [Article in Japanese].
 
Willital GH, Heine H. 1994. Efficacy of Contractubex gel in the treatment of fresh scars after thoracic surgery in children and adolescents. Int J Clin Pharmacol Res 1994; 14(5-6): 193-202.
    
             
     
Additional Information:     
     
Allantoin Research:

Willital GH, Heine H. 1994. Efficacy of Contractubex gel in the treatment of fresh scars after thoracic surgery in children and adolescents. Int J Clin Pharmacol Res 1994; 14(5-6): 193-202.
 
Clinic and Polyclinic for Surgery of Children, Westphalian Wilhelm University, Munster, Germany.
 
Scar development was investigated in 45 young patients who had undergone thoracic surgery. Patients were randomly assigned either to a group which was treated topically with Contractubex gel (Merz + Co., D-Frankfurt/Main), containing 10% onion extract, 50/U of sodium heparin per one g of gel and 1% allantoin, or to a group receiving no treatment. The treatment began on average 26 days after the operation and was continued for one year. The scars of all treated and untreated patients were evaluated at monthly intervals. The appearance of the scar, including scar type and scar size as well as scar colour, was assessed by the physician. A reduction of the increase of scar width was seen in the Contractubex-treated group as compared with the untreated group. Further, physiological scars and skin-coloured scars were more frequent in the treated group than in the untreated group. Hypertrophic or keloidal scars were less frequent in the treated group. No differences in scar length and scar height were seen. At the end of the observation period, the clinical course of scar development was rated as “very good” or “good” in more than 90% of the treated patients, “good” in less than 40% and “moderate” or “bad” in more than 60% of the untreated cases. The tolerability of the drug was “good” or “very good” in all cases. In conclusion, Contractubex gel is useful in scar treatment after thoracic surgery.

Cajkovac M, Oremovic L, Cajkovac V. 1991. Influence of emulsoid vehicle on the release and activity of allantoin. Pharmazie 1992 Jan; 47(1): 39-43.
 
Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Zagreb.
 
Samples which contain 2% (w/w) of allantoin in various emulsified vehicles were prepared and characterized. The influence of vehicle on releasing and diffusion of allantoin through semipermeable membrane into an aqueous medium was examined and the quantity of released allantoin was estimated spectrophotometrically. The best results were achieved with ambiphilic vehicle emulsified with complex Tagat S-Tegin M which in the aqueous phase contained propylene glycol (sample A2). On the contrary, with both lanacolic vehicles, the poorest results were achieved in vitro. On the basis of the results for clinical evaluation, the best preparation was chosen (A2) and the preparation with lanacolic vehicle which contains propylene glycol (B2). Before the application of samples, each patient was tested for irritation and sensitization. All test were negative. During further clinical examinations on patients suffering from psoriasis an open double trial for the duration of 14 d was performed. For the evaluation of the efficacy of the examined preparations, objective parameters of the clinical picture were observed (the state of hyperkeratosis, of erythema and infiltration) as well as subjective parameters which were evaluated by the patients themselves. When the in vitro results are compared with clinical estimation, it is evident that they correspond only when characteristics of the preparation are estimated by patients (smearing, absorption and feeling on the skin), because the best preparation was in these cases A2. Both preparations are equally good when regression of subjective symptoms is evaluated (itching and burning). In the objective evaluation of the regression of visible symptoms, such as hyperkeratosis and erythema, results of the clinical experiment do not correspond with results in vitro.
 
Sakuma K, Ogawa M, Kimura M, Yamamoto K, Ogihara M. 1998. [Inhibitory effects of shimotsu-to, a traditional Chinese herbal prescription, on ultraviolet radiation-induced cell damage and prostaglandin E2 release in cultured Swiss 3T3 cells]. Yakugaku Zasshi 1998 Jun; 118(6): 241-7. [Article in Japanese].
 
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
 
We have investigated the effects of Shimotsu-to, a traditional Chinese herbal prescription (Kampo medicine), on ultraviolet (UV) radiation-induced cell damage and prostaglandin E2 (PGE2) release in cultured Swiss 3T3 cells to examine the anti-inflammatory mechanism of Shimotsu-to. Short-term UV irradiation significantly induced cell damage and stimulated PGE2 release in Swiss 3T3 cells cultured for 4 h. The UV-radiation-induced cell damage and the stimulation of PGE2 release were significantly suppressed by the treatment with Shimotsu-to. Among the single crude drug components of Shimotsu-to, Rehmanniae Radix showed significant protective effects against UV-radiation-induced cell damage and PGE2 release. Other synthetic anti-inflammatory agents, such as dexamethasone, dipotassium glycyrrhizinate and allantoin also protected against UV-induced cell damage and inhibited PGE2 release in cultured Swiss 3T3 cells. These results suggest that the anti-inflammatory mechanism of Shimotsu-to against UV-irradiated erythema (acute skin inflammation) in guinea pigs in vivo may be mediated by the inhibition of PGE2 release from cutaneous target cells.
 
Scott LJ, Dunn CJ, Goa KL. 2001. Calcipotriol ointment. A review of its use in the management of psoriasis. Am J Clin Dermatol 2001; 2(2): 95-120.
 
Adis International Inc., Langhorne, Pennsylvania, USA. demail@adis.com
 
Calcipotriol, a vitamin D3 analog, acts not only to inhibit cell proliferation and enhance cell differentiation in the skin of patients with psoriasis, but also appears to have effects on immunologic markers that are thought to play a role in the etiology of the disease. In several well designed, short term studies in adults, calcipotriol ointment 50 micrograms/g twice daily provided similar or superior efficacy to several other antipsoriatic agents in adult patients with mild to moderate psoriasis. In patients with nonscalp psoriasis, the drug provided superior efficacy to twice daily placebo (vehicle ointment), twice daily fluocinonide 500 micrograms/g, once daily tacalcitol 4 micrograms/g and twice daily coal tar 5% plus allantoin 2% and hydrocortisone 0.5%. Furthermore, calcipotriol therapy generally provided superior efficacy to twice daily betamethasone valerate 1 to 1.2 mg/g or once daily dithranol 1 to 20 mg/g, and similar efficacy to twice daily betamethasone dipropionate plus salicylic acid or once daily maxacalcitol 6 to 50 micrograms/g. Limited data indicated that calcipotriol ointment 50 micrograms/g also improved overall disease severity in children. In combination with other antipsoriatic agents [acitretin, cyclosporine, betamethasone valerate, halobetasol (ulobetasol)], ultraviolet B or psoralen ultraviolet A (PUVA) phototherapy, calcipotriol ointment 50 micrograms/g twice daily improved the beneficial effects of these drugs on overall disease severity in adult patients with moderate to severe psoriasis. Furthermore, in separate trials, calcipotriol combination therapy reduced the dosage of acitretin required to achieve clearance of psoriasis and the duration of PUVA and dosage of UVA phototherapy, potentially improving the benefit/risk ratio for these other antipsoriatic treatments. Calcipotriol was generally well tolerated in short and long term studies in adult patients, with the majority of adverse events being mild to moderate in intensity and transient. The most common adverse events associated with calcipotriol therapy were dermatologic in nature and included lesional or perilesional irritations, face and scalp irritations, worsening of psoriasis and miscellaneous dermatologic events. Notably, there have been very few reports of patients developing hypercalcemia or hypercalciuria during calcipotriol therapy, with most occurring in patients who exceeded the recommended dosage of 100 g/week. Although data in children are limited, the drug was well tolerated with the nature and incidence of adverse effects similar to those observed in adult patients. CONCLUSIONS: Extensive clinical experience, along with several short and long term clinical trials, has shown calcipotriol ointment to be an effective and well tolerated topical agent in adult patients with psoriasis. In addition, calcipotriol ointment proved beneficial in combination with other topical, phototherapy or systemic antipsoriatic treatments, reducing the dosage and/or duration of some of these treatments and potentially improving their benefit/risk ratio. Calcipotriol ointment is valuable as a first- or second-line therapy option for the management of mild to moderate psoriasis and in combination with other antipsoriatic agents for more severe psoriasis.
 
Pinheiro N. 1997. Comparative effects of calcipotriol ointment (50 micrograms/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream in treating plaque psoriasis. Br J Clin Pract 1997 Jan-Feb; 51(1): 16-9.
 
The comparative efficacy, tolerability and acceptability of calcipotriol ointment (50 micrograms/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream were determined in 122 patients with chronic plaque psoriasis affecting at least 100 cm2 of skin. Both preparations were applied twice daily for up to 8 weeks. At the end of treatment, investigators considered calcipotriol significantly more effective in the proportion of patients 'cleared' or 'markedly improved' (calcipotriol 72.3%, coal tar/allantoin/hydrocortisone 49.1%: p < 0.02). Calcipotriol was also superior in reducing the total sign score (p = 0.002), and individual scores for scaliness (p < 0.0001) and thickness (p = 0.001). The proportion of patients with less than 100 cm2 of affected skin at the end of treatment was significantly greater in the calcipotriol group (p < 0.05). Patients considered calcipotriol significantly more effective overall (p < 0.02) and in reducing flakiness/scaliness of skin (p = 0.001). Adverse events, most of which were application related and mild to moderate, were recorded in 15 (23.1%) patients using calcipotriol and in 10 (17.5%) patients using coal tar/allantoin/hydrocortisone (n.s.), and contributed to treatment withdrawal in one (1.5%) and three (5.3%) patients, respectively. Wilson TD, Steck WF. 2000. A modified HET-CAM assay approach to the assessment of anti-irritant properties of plant extracts. Food Chem Toxicol 2000 Oct; 38(10): 867-72.
 
Fytokem Products Inc., Saskatoon, Canada.
 
Hen's egg–chorioallantoic membranes were used to screen for and assess anti-irritant properties among aqueous extracts of plants (HET-CAM tests), in connection with searches for plant-derived substances with topical anti-irritant action. The main question to be answered was whether CAM-assay screening of plant extracts could provide a useful route to identifying promising anti-irritant extracts for follow-up clinical testing. To be useful, the method would have to flag materials with strong anti-irritant properties, and would have to avoid registering false negatives. The tests conducted provided positive indications. We measured the delays in onset of three manifestations of membrane irritation-vascular hemorrhaging, membrane lysis and membrane coagulation-observed with test substances relative to positive controls. Aqueous 15% lactic acid, a commonly used irritant in direct tests on human skin, was employed as the test irritant in this study. The ratio [irritation onset times after test substance pre-treatment]:[onset times without test substance pretreatment] was used to measure the anti-irritant power of test substances. A scoring notation was devised for this which treats the delay parameters as independent effects. Most tested plant extracts showed no significant irritant or anti-irritant effects. Among the apparently anti-irritant plant extracts (approx. 10% of all those tested), most showed their greatest effect against hemorrhaging. Lesser but still readily measurable effects against membrane lysis and coagulation were also observed in nearly all the apparently anti-irritant extracts. Two of the tested extracts proved to be membrane irritants. Some key CAM assay results were compared with results obtained in direct tests on human skin using the same test irritant (15% lactic acid). In these comparative tests on skin, an essentially similar pattern of efficacy was obtained, with the plant extract deemed best in the CAM screenings, outperforming the benchmark anti-irritant hydrocortisone. From these initial results it appears that physiological CAM assays may prove useful in screening natural materials for anti-irritant properties, as alternatives to mechanism-dependent biochemical assays, or expensive direct screening tests on human subjects. Further work remains to extend the CAM screening approach to irritants other than lactic acid, and to assess its quantitative powers of prediction of topical anti-irritancy.