SANGRE DE GRADO
Blood of the Dragon, Crofelemer, Croton lechleri, Drago, Dragon's Blood, Dragon's Blood Croton, Lan-Hiqui, Laniqui, Palo de Grado, Sang de Dragon, Sangre de Drago, Sangre de Dragon, Sangre de Grado, Sangue de Agua, Sangue de Drago, SP 303, SP-303, Taspine.
Overview InformationA chemical in sangre de grado known as crofelemer (SP-303) was approved as a drug by the U.S. Food and Drug Administration (FDA) for diarrhea in people with HIV/AIDS. It is also sometimes used for travelers' diarrhea and irritable bowel syndrome (IBS), but it has not been approved by the FDA for these uses. Sangra de grado supplement products have not been studied for these conditions.
Sangre de grado supplements are sometimes used for the common cold, upper airway infections, ulcers, and many other conditions. But there is no good scientific evidence to support these uses.
How does it work?Sangre de grado appears to help diarrhea by slowing down the amount of water that is lost through the intestines. It might also prevent the movement of some viruses into cells. It might also block pain signals in the nerves.
Uses & Effectiveness
Possibly Effective for
- Diarrhea in people with HIV/AIDS. Crofelemer is a chemical from sangre de grado. Research shows that taking crofelemer reduces diarrhea in people with AIDS-related diarrhea. This product is approved by the U.S. Food and Drug Administration for this condition.
- Genital herpes. Crofelemer is a chemical from sangre de grado. Research shows that applying crofelemer to the skin helps treat genital and anal herpes outbreaks in people with AIDS. But it might not be helpful for herpes outbreaks that do not respond to acyclovir, a drug used to treat herpes infections.
- Traveler's diarrhea. Crofelemer is a chemical from sangre de grado. Research shows that taking crofelemer helps traveler's diarrhea go away about 6-8 hours faster.
Possibly Ineffective for
- A long-term disorder of the large intestines that causes stomach pain (irritable bowel syndrome or IBS). Crofelemer is a chemical from sangre de grado. Research shows that taking crofelemer does not reduce pain or diarrhea in people with diarrhea-predominant IBS (IBS-D).
Insufficient Evidence for
- Insect bite. Early research shows that applying sangre de grado to the skin relieves symptoms of insect bites and skin irritation due to plants.
- Bleeding gums.
- Bone cancer.
- Common cold.
- Diarrhea caused by cancer drug treatment.
- Diarrhea in people taking antibiotics (antibiotic-associated diarrhea).
- Eczema (atopic dermatitis).
- Infection of the gastrointestinal tract by bacteria called Clostridium difficile.
- Menstrual cramps (dysmenorrhea).
- Mouth and throat ulcers.
- Stomach ulcers.
- Swelling (inflammation) of the vagina (vaginitis).
- Upper airway infection.
- Wound healing.
- Other conditions.
Side Effects & SafetyWhen taken by mouth: It is LIKELY SAFE to take a specific chemical from sangre de grado called crofelemer (SP-303). Some people have reported stomach pain, gas, headache, and bronchitis when taking crofelemer (SP-303). There isn't enough reliable information to know if sangre de grado itself is safe or what the side effects might be.
When applied to the skin: It is POSSIBLY SAFE to apply a chemical from sangre de grado, called crofelemer (SP-303), directly to the skin. Some people have reported pain and burning when applying this product to the skin. There isn't enough reliable information to know if sangre de grado itself is safe or what the side effects might be.
Special Precautions & Warnings:Pregnancy and breast-feeding: There isn't enough reliable information to know if sangre de grado is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.
A type of blood cancer called leukemia: Sangre de grado might make this condition worse. Avoid using sangre de grado if you have leukemia.
We currently have no information for SANGRE DE GRADO Interactions.
The following doses have been studied in scientific research:
- For diarrhea in people with HIV/AIDS: A prescription-only product (Fulyzaq; Mytesi) that contains a specific chemical found in sangre de grado (crofelemer) has been taken as 125 mg twice daily. This same product has also been used in a dose of 500 mg every 6 hours for 4 days, but this dose is not approved by the US Food and Drug Administration.
- For travelers' diarrhea: 125-500 mg of crofelemer (SP-303), a chemical isolated from sangre de grado, four times daily for 2 days has been used.
- For genital herpes: A specific ointment containing 15% crofelemer (SP-303), a chemical found in sangre de grado, has been applied to herpes lesions three times daily for 21 days.
- De, Marino S., Gala, F., Zollo, F., Vitalini, S., Fico, G., Visioli, F., and Iorizzi, M. Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity. Molecules. 2008;13(6):1219-1229. View abstract.
- Desmarchelier, C. J. and de Moraes Barros, S. B. Pharmacological activity of South American plants: effects on spontaneous in vivo lipid peroxidation. Phytother.Res. 2003;17(1):80-82. View abstract.
- DiCesare, D., DuPont, H. L., Mathewson, J. J., Ashley, D., Martinez-Sandoval, F., Pennington, J. E., and Porter, S. B. A double blind, randomized, placebo-controlled study of SP-303 (Provir) in the symptomatic treatment of acute diarrhea among travelers to Jamaica and Mexico. Am.J.Gastroenterol. 2002;97(10):2585-2588. View abstract.
- Froldi, G., Zagotto, G., Filippini, R., Montopoli, M., Dorigo, P., and Caparrotta, L. Activity of sap from Croton lechleri on rat vascular and gastric smooth muscles. Phytomedicine. 2009;16(8):768-775. View abstract.
- Gonzales, G. F. and Valerio, L. G., Jr. Medicinal plants from Peru: a review of plants as potential agents against cancer. Anticancer Agents Med.Chem. 2006;6(5):429-444. View abstract.
- Jones, K. Review of sangre de drago (Croton lechleri)--a South American tree sap in the treatment of diarrhea, inflammation, insect bites, viral infections, and wounds: traditional uses to clinical research. J.Altern.Complement Med. 2003;9(6):877-896. View abstract.
- Lopes, M. I., Saffi, J., Echeverrigaray, S., Henriques, J. A., and Salvador, M. Mutagenic and antioxidant activities of Croton lechleri sap in biological systems. J.Ethnopharmacol. 2004;95(2-3):437-445. View abstract.
- Milanowski, D. J., Winter, R. E., Elvin-Lewis, M. P., and Lewis, W. H. Geographic distribution of three alkaloid chemotypes of Croton lechleri. J.Nat.Prod. 2002;65(6):814-819. View abstract.
- Miller, M. J., MacNaughton, W. K., Zhang, X. J., Thompson, J. H., Charbonnet, R. M., Bobrowski, P., Lao, J., Trentacosti, A. M., and Sandoval, M. Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine sangre de grado. Am.J.Physiol Gastrointest.Liver Physiol 2000;279(1):G192-G200. View abstract.
- Miller, M. J., Vergnolle, N., McKnight, W., Musah, R. A., Davison, C. A., Trentacosti, A. M., Thompson, J. H., Sandoval, M., and Wallace, J. L. Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado. J.Invest Dermatol. 2001;117(3):725-730. View abstract.
- Pereira, U., Garcia-Le, Gal C., Le, Gal G., Boulais, N., Lebonvallet, N., Dorange, G., Lefeuvre, L., Gougerot, A., and Misery, L. Effects of sangre de drago in an in vitro model of cutaneous neurogenic inflammation. Exp.Dermatol. 2010;19(9):796-799. View abstract.
- Porras-Reyes, B. H., Lewis, W. H., Roman, J., Simchowitz, L., and Mustoe, T. A. Enhancement of wound healing by the alkaloid taspine defining mechanism of action. Proc.Soc.Exp.Biol.Med. 1993;203(1):18-25. View abstract.
- Risco, E., Ghia, F., Vila, R., Iglesias, J., Alvarez, E., and Canigueral, S. Immunomodulatory activity and chemical characterisation of sangre de drago (dragon's blood) from Croton lechleri. Planta Med. 2003;69(9):785-794. View abstract.
- Rossi, D., Bruni, R., Bianchi, N., Chiarabelli, C., Gambari, R., Medici, A., Lista, A., and Paganetto, G. Evaluation of the mutagenic, antimutagenic and antiproliferative potential of Croton lechleri (Muell. Arg.) latex. Phytomedicine. 2003;10(2-3):139-144. View abstract.
- Sandoval, M., Okuhama, N. N., Clark, M., Angeles, F. M., Lao, J., Bustamante, S., and Miller, M. J. Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells. J.Ethnopharmacol. 2002;80(2-3):121-129. View abstract.
- Tradtrantip, L., Namkung, W., and Verkman, A. S. Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol.Pharmacol. 2010;77(1):69-78. View abstract.
- Tran, C. D., Butler, R. N., and Miller, M. J. The role of Amazonian herbal medicine Sangre de Grado in Helicobacter pylori infection and its association with metallothionein expression. Helicobacter. 2006;11(2):134-135. View abstract.
- Williams, J. E. Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado. Altern.Med.Rev. 2001;6(6):567-579. View abstract.
- Alonso-Castro AJ, Ortiz-Sanchez E, Dominguez F, et al. Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae). J Ethnopharmacol 2012;140(2):438-42. View abstract.
- Barnard DL, Huffman JH, Meyerson LR, Sidwell RW. Mode of inhibition of respiratory syncytial virus by a plant flavonoid, SP-303. Chemotherapy 1993;39:212-7. View abstract.
- Barnard DL, Smee DF, Huffman JH, et al. Antiherpesvirus activity and mode of action of SP-303, a novel plant flavonoid. Chemotherapy 1993;39:203-11. View abstract.
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- Crofelemer. FDA-Approved Drug Products. FDA Web site. Accessed 6/30/2017. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/.
- Desmarchelier C, Witting Schaus F, Coussio J, Cicca G. Effects of Sangre de Drago from Croton lechleri Muell.-Arg. on the production of active oxygen radicals. J Ethnopharmacol 1997;58:103-8. View abstract.
- Dicesare D, Dupont HL, Mathewson JJ, et al. A double-blind randomized, placebo-controlled study of SP-303 (Provir) in the symptomatic treatment of acute diarrhea among travelers to Mexico and Jamaica. Infectious Diseases Society of America Annual Meeting, 1998 (abstract).
- Frampton JE. Crofelemer: a review of its use in the management of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Drugs 2013;73(10):1121-9. View abstract.
- Fulyzaq [package insert]. Salix Pharmaceuticals, Inc.; Raleigh, NC: December 2012. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202292s000lbl.pdf.
- Gabriel SE, Davenport SE, Steagall RJ, et al. A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion. Am J Physiol 1999;276:G58-G63. View abstract.
- Gilbert BE, Wyde PR, Wilson SZ, Meyerson LR. SP-303 small-particle aerosol treatment of influenza A virus infection in mice and respiratory syncytial virus infection in cotton rats. Antiviral Res 1993;21:37-45. View abstract.
- Holodniy M, Koch J, Mistal M, et al. A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS. Am J Gastroenterol 1999;94:3267-73. View abstract.
- MacArthur RD, Hawkins T, Brown SJ, et al. Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study. HIV Clin Trials 2013;14(6):261-73. View abstract.
- Mangel AW, Chaturvedi P. Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel syndrome patients. Digestion 2008;78(4):180-6. View abstract.
- Miller MJ, Vergnolle N, Wallace JL, et al. Sangre de grado is a potent and unique inhibitor of neurogenic inflammation and promotes healing in experimental necrotizing enterocolitis. Pediatric Academic Soc and Acad Pediatrics Joint Mtg, May 12-6 2000:Abstract 979.
- Nee J, Salley K, Ludwig AG, et al. Randomized clinical trial: crofelemer treatment in women with diarrhea-predominant irritable bowel syndrome. Clin Transl Gastroenterol. 2019;10(12):e00110. View abstract.
- Orozco-Topete R, Sierra-Madero J, Cano-Dominguez C, et al. Safety and efficacy of Virend for topical treatment of genital and anal herpes simplex lesions in patients with AIDS. Antiviral Res 1997;35:91-103. View abstract.
- Perdue GP, Blomster RN, Blake DA, Farnsworth NR. South American plants II: taspine isolation and anti-inflammatory activity. J Pharm Sci 1979;68:124-6. View abstract.
- Pieters L, de Bruyne T, Claeys M, et al. Isolation of a dihydrobenzofuran lignan from South American dragon's blood (Croton spp.) as an inhibitor of cell proliferation. J Nat Prod 1993;56:899-906. View abstract.
- Raintree Nutrition. Sangre de Grado website: www.rain-tree.com/sangre.htm (Accessed 31 January 2000).
- Safrin S, McKinley G, McKeough M, et al. Treatment of acyclovir-unresponsive cutaneous herpes simplex virus infection with topically applied SP-303. Antiviral Res 1994;25:185-92. View abstract.
- Sidwell RW, Huffman JH, Moscon BJ, Warren RP. Influenza virus-inhibitory effects of intraperitoneally and aerosol-administered SP-303, a plant flavonoid. Chemotherapy 1994;40:42-50. View abstract.
- Styczynski J, Wysocki M. Alternative medicine remedies might stimulate viability of leukemic cells. Pediatr Blood Cancer 2006;46:94-8. View abstract.
- USDA, ARS, National Genetic Resources Program. Germplasm Resources Information Network - (GRIN). Taxon: Croton lechleri mull. Arg website: www.ars-grin.gov/cgi-bin/npgs/html/tax_search.pl?croton+lechleri (Accessed 31 January 2000).
- Vaisberg AJ, Milla M, Planas MC, et al. Taspine is the cicatrizant principle in Sangre de Grado extracted from Croton lechleri. Planta Med 1989;55:140-3. View abstract.
- Wyde PR, Ambrose MW, Meyerson LR, Gilbert BE. The antiviral activity of SP-303, a natural polyphenolic polymer, against respiratory syncytial and parainfluenza type 3 viruses in cotton rats. Antiviral Res 1993;20:145-54. View abstract.
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