Thuốc Laminaria

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Thuốc Laminaria
Thuốc Laminaria

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Scientific Name(s): Laminaria bracteata Ag., Laminaria digitata (L.) Lamour.
Common Name(s): Brown algae, Devil’s apron, Kelp, Kombu, Lamicel, Laminaria, Ne-kombu, Sea girdles

Medically reviewed by Holevn.org. Last updated on Jan 20, 2020.

Clinical Overview

Use

Laminaria has been used traditionally as a hygroscopic cervical dilator and inducer of labor, and commercial products are available for this purpose. The basal parts of the blades of Laminaria japonica and Laminaria angustata have been used as a hypotensive agent (ne-kombu) in Japanese folk medicine.

Dosing

Clinical trials are lacking to provide dosing information for uses other than mechanical cervical dilation.

Contraindications

Use is contraindicated during pregnancy.

Pregnancy/Lactation

Laminaria dilators have been used to dilate the cervix and to induce labor in abortions. Information on the use of laminaria for other purposes during pregnancy is lacking. Avoid use.

Interactions

None well documented.

Adverse Reactions

There is a risk of laminaria dilators becoming trapped and fragmenting. Cases of hypersensitivity, including anaphylaxis, have also been reported.

Toxicology

Information is lacking.

Scientific Family

  • Laminariaceae

Botany

Laminaria, a genus of brown algae commonly known as “kelp,” is found primarily in the cold waters of the North Atlantic and North Pacific oceans.1

History

Laminaria for cervical dilation is used in the form of “tents,” usually made of any hygroscopic (readily absorbs water) material, that are placed to maintain the opening or cause dilation. Dilators are made from the dried stems of laminaria seaweeds. When dried and rounded into a stick-like shape, the dilators are approximately 6 cm (2.5 inches) long with a diameter of 0.3 to 0.5 cm. A strong thread is attached to one end, and a collar prevents migration into the uterus. The stem is hygroscopic and can swell 3 to 5 times its original diameter within 12 to 24 hours. Other natural products used as tents for various purposes include sponges, dried corn stalks, slippery elm bark, and tupelo wood.2 Hollow laminaria tents were developed in the 1800s to improve uterine drainage, and laminaria coated with wax was designed to release antiseptics as the wax melted.

Tents fell into disuse because of complications caused by infections. This was especially evident in tents derived from land plants because of the inability of sterilization to inactivate Clostridium spores, the causative agents of tetanus, botulism, and gas gangrene. Although laminaria from the ocean harbors relatively nonpathogenic bacteria, polluted waters and poor packaging negated the advantage. However, with the advent of ethylene oxide and gamma irradiation sterilization techniques, interest in laminaria dilators returned.

L. bracteata Ag. (L. japonica Aresch) is commonly used in soup, candy, and sushi, or is eaten with rice or as a salad. The plant is known as kombu in the Far East and is cultivated in China, Korea, and Japan.3

Chemistry

Laminarin (laminaran) is a polysaccharide found in laminaria sap. Soluble and insoluble forms are found in algae.4, 5 Kelp are rich in algin, a high molecular weight polysaccharide that forms viscous colloidal solutions or gels in water. This property has led to the use of kelp derivatives as bulk laxatives.6 The constituents of laminaria also include iodine, potassium, magnesium, calcium, and iron.7, 8, 9

Uses and Pharmacology

Cervical ripening

Laminaria dilators have been used to dilate the cervix and to induce labor in abortions. When inserted into the cervix, laminaria dilators absorb surrounding moisture and gradually swell to a diameter of approximately one-half inch. While most of the swelling occurs in the first 4 to 6 hours, it may continue for up to 24 hours. Because this is a gradual process, the patient rarely notices pain. At the same time, the cervix is induced to ripening (becoming soft and flexible). The effect is often limited to local cervical ripening; however, stimulation of the cervix can induce labor.

The mechanism of action may be similar to that of a foreign body that, when inserted into the cervical canal, disturbs the normal chorioamniotic balance and initiates a cascade of prostaglandin synthesis. This in turn has myometrial-contracting and cervical-ripening effects.10 Mediation by arachidonic acid has been suggested, but is not supported by evidence.11 Cervical dilation may also be the result of partial placental detachment induced by laminaria.12

Clinical data

A Cochrane review of mechanical methods of labor induction considered trials of laminaria versus placebo, prostaglandins, oxytocin, or extra-amniotic infusion. Most trials were small and evaluated different outcomes, making comparisons difficult. Thus, the review used risk of cesarian delivery as the comparator outcome measure. The lack of blinding in these trials must also be considered a potential source of bias.13

In trials of laminaria versus placebo, no evidence exists of increased risk of cesarian delivery. Rates of cesarian delivery were the same for laminaria versus oxytocin and for laminaria versus extra-amniotic infusion. Likewise, in trials versus prostaglandins, the risk of cesarian delivery was the same for both groups; however, laminaria caused less hyperstimulation with fetal heart rate changes. No added benefit was found in trials of laminaria added to prostaglandins or to oxytocin.13

Trials subsequent to the Cochrane review, which included trials up to 2001, have largely found similar results.14 More recent trials have evaluated laminaria versus misoprostol and mifepristone, finding similar efficacy, but showing an increase in cost, induction times, and pain associated with laminaria.15, 16, 17, 18 The lack of blinding remains a methodological issue.

The potential exists for adverse outcomes with laminaria dilator use, especially infectious morbidity; endometritis, fetal sepsis, septic shock, and anaphylaxis have been reported.10, 19, 20, 21 A review of laminaria in cervical ripening found no difference in maternal infection rates for trials reporting infection-related outcomes, but the number of trials was small.22 A further review concluded that serious infection and anaphylaxis were rare with commercial laminaria devices.23 In a review of trials using laminaria in mid-trimester abortions, no increased risk of clinically important subsequent pregnancy complications was found.24

Other uses

Sulfated polysaccharides from marine Laminaria cichoroides exert anticoagulant activity similar to that of heparin, but clinical relevance is unclear.25, 26

The basal parts of the blades of L. japonica and L. angustata have been used as a hypotensive agent (ne-kombu) in Japanese folk medicine.27 Chemical analysis of the blades suggests that histamine and the amino acid laminine may be responsible for this hypotensive effect.28, 29

Alginate-containing algae reduce the absorption of radioactive strontium in animals and humans and are used in the management of radioactive intoxications.30

Dosing

Clinical trials are lacking to provide dosing information for uses other than mechanical cervical dilation.

Pregnancy / Lactation

Laminaria dilators have been used to dilate the cervix and to induce labor in abortions. Information on the use of laminaria for other purposes during pregnancy is lacking. Avoid use.

Interactions

None well documented.

Adverse Reactions

There is a risk of laminaria dilators becoming trapped and fragmenting.23, 31 Synthetic laminaria dilators prepared from hydrophilic polymers provide increased levels of structural stability.32

Increases in serum thyrotropin were observed in healthy volunteers who consumed kombu 15 g daily for 7 to 10 days. Long-term ingestion (55 to 87 days) led to abnormally elevated serum thyrotropin levels, but these returned to normal on discontinuation of consumption. The effect was attributed to the iodine content of the seaweed. Reports of hypothyroidism exist among Japanese populations, but causality has not been established.27

A case report of laminaria hypersensitivity was followed up with a review conducted through August 2014 of reported cases of hypersensitivity to laminaria. Of the 10 reactions documented, 8 met the criteria for anaphylaxis. No deaths in the female patients were reported and most patients experienced prompt resolution with antihistamines and corticosteroids.33

Toxicology

Information is lacking.

Index Terms

  • Kelp

References

1. Morton JF. Major Medicinal Plants: Botany, Culture, and Uses. Springfield, IL: Thomas; 1977.2. Newton BW. Laminaria tent: relic of the past or modern medical device? Am J Obstet Gynecol. 1972;113(4):442-448.46366233. Johansen HW, Akioka H. Salad from the sea. Sea Front. 1988;34:136.4. Windholz M, Budavari S, Blumetti RF, Otterbein ES, eds. The Merck Index; An Encyclopedia of Chemicals, Drugs, and Biologicals. 10th ed. Rahway, NJ: Merck & Co; 1983.5. Zvyagintseva TN, Shevchenko NM, Chizhou AO, Krupnova TN, Sundukova EV, Isakov VV. Water-soluble polysaccharides of some far-eastern brown seaweeds. Distribution, structure, and their dependence on the development conditions. J Exp Mar Biol Ecol. 2003;294(1):1-13.6. Tyler VE. The New Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. Philadelphia, PA: GF Stickley Co; 1987.7. The Drug & Natural Medicine Advisor: The Complete Guide to Alternative & Conventional Medications. Alexandria, VA: Time-Life Books; 1997.8. Lininger SW, Wright JV, eds. The Natural Pharmacy. Rocklin, CA: Prima Publishing; 1998.9. van Netten C, Hoption Cann SA, Morley DR, van Netten JP. Elemental and radioactive analysis of commercially available seaweed. Sci Total Environ. 2000;255(1-3):169-175.1089840410. Kazzi GM, Bottoms SF, Rosen MG. Efficacy and safety of Laminaria digitata for preinduction ripening of the cervix. Obstet Gynecol. 1982;60(4):440-443.712193111. Crawford MA, Casperd NM, Sinclair AJ. The long chain metabolites of linoleic avid linoleic acids in liver and brain in herbivores and carnivores. Comp Biochem Physiol B. 1976;54(3):395-401.127780812. Jonasson A, Larsson B, Lecander I, Astedt B. Placental and decidual u-PA, t-PA, PAI-1, and PAI-2 concentrations, as affected by cervical dilatation with laminaria tents or Hegar dilators. Thromb Res. 1989;53(2):91-97.249368513. Boulvain M, Kelly A, Lohse C, Stan C, Irion O. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2001;(4):CD001233.1168710114. Almog B, Levin I, Winkler N, et al. The contribution of laminaria placement for cervical ripening in second trimester termination of pregnancy induced by intra-amniotic injection of prostaglandin F(2)alpha followed by concentrated oxytocin infusion. Eur J Obstet Gynecol Reprod Biol. 2005;118(1):32-35.1559626915. Prairie BA, Lauria MR, Kapp N, Mackenzie T, Baker ER, George KE. Mifepristone versus laminaria: a randomized controlled trial of cervical ripening in midtrimester termination. Contraception. 2007;76(5):383-388.1796386416. Darwish AM, Ahmad AM, Mohammad AM. Cervical priming prior to operative hysteroscopy: a randomized comparison of laminaria versus misoprostol. Hum Reprod. 2004;19(10):2391-2394.1533360717. Edelman AB, Buckmaster JG, Goetsch MF, Nichols MD, Jensen JT. Cervical preparation using laminaria with adjunctive buccal misoprostol before second-trimester dilation and evacuation procedures: a randomized clinical trial. Am J Obstet Gynecol. 2006;194(2):425-430.1645864018. Borgatta L, Chen AY, Vragovic O, Stubblefield PG, Magloire CA. A randomized clinical trial of the addition of laminaria to misoprostol and hypertonic saline for second-trimester induction abortion. Contraception. 2005;72(5):358-361.1624666219. Lin SY, Cheng WF, Su YN, Chen CA, Lee CN. Septic shock after intracervical laminaria insertion. Taiwan J Obstet Gynecol. 2006;45(1):76-78.1727221620. Kim SH, Chang YH, Kim WK, et al. Two cases of anaphylaxis after laminaria insertion. J Korean Med Sci. 2003;18(6):886-888.1467644921. Knowles SR, Djordjevic K, Binkley K, Weber EA. Allergic anaphylaxis to Laminaria. Allergy. 2002;57(4):370.1190637522. Heinemann J, Gillen G, Sanchez-Ramos L, Kaunitz AM. Do mechanical methods of cervical ripening increase infectious morbidity? A systematic review. Am J Obstet Gynecol. 2008;199(2):177-188.1867466123. Lichtenberg ES. Complications of osmotic dilators. Obstet Gynecol Surv. 2004;59(7):528-536.1519927124. Jackson JE, Grobman WA, Haney E, Casele H. Mid-trimester dilation and evacuation with laminaria does not increase the risk for severe subsequent pregnancy complications. Int J Gynaecol Obstet. 2007;96(1):12-15.1719620525. Drozd NN, Tolstenkov AS, Makarov VA, et al. Pharmacodynamic parameters of anticoagulants based on sulfated polysaccharides from marine algae. Bull Exp Biol Med. 2006;142(5):591-593.1741547026. Yoon SJ, Pyun YR, Hwang JK, Mourao PA. A sulfated fucan from the brown alga Laminaria cichorioides has mainly heparin cofactor II-dependent anticoagulant activity. Carbohydr Res. 2007;342(15):2326-2330.1763128227. Miyai K, Tokushige T, Kondo M; Iodine Research Group. Suppression of thyroid function during ingestion of seaweed “Kombu” (Laminaria japonoca ) in normal Japanese adults. Endocr J. 2008;55(6):1103-1108.1868995428. Funayama S, Hikino H. Hypotensive principle of Laminaria and allied seaweeds. Planta Med. 1981;41(1):29-33.723254829. Chiu KW, Fung AY. The cardiovascular effects of green beans (Phaseolus aureus ), common rue (Ruta graveolens), and kelp (Laminaria japonica) in rats. Gen Pharmacol. 1997;29(5):859-862.934733830. Gong YF, Huang ZJ, Qiang MY, et al. Suppression of radioactive strontium absorption by sodium alginate in animals and human subjects. Biomed Environ Sci. 1991;4(3):273-282.176421731. Borgatta L, Barad D. Prolonged retention of laminaria fragments: an unusual complication of laminaria usage. Obstet Gynecol. 1991;78(5 pt 2):988-990.192324932. Chvapil M, Droegemueller W, Meyer T, Macsalka R, Stoy V, Suciu T. New synthetic laminaria. Obstet Gynecol. 1982;60(6):729-733.714527733. Sierra T, Figueroa MM, Chen KT, Lunde B, Jacobs A. Hypersensitivity to laminaria: a case report and review of literature. Contraception. 2015;91(4):353-355.25595541

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Further information

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Reference from: https://www.drugs.com/npp/laminaria.html

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