研究開発領域 優れた安全性と高い機能性を有する、医療用接着剤“LYDEX®”の開発

Development of medical adhesive,“LYDEX®”,which has excellent safety and functionality.

LYDEX® is made from dextran, medical polymer material of which safety is already demonstrated and poly lysine, which is food additive. Both consist of aldehyde dextran and carboxylated poly lysine. By mixing these two ingredients at appropriate mixing rate, pharmaceutical preparation, which has high adhesion, sealant effect and hemostatic effect is obtained. It is dissolved and disappears properly inside body after achieving its effect.

Merits of “LYDEX®”

LYDEX® not only possesses property of high adhesion and flexibility but also has excellent safety because it is made from infection-free material. And since various dosage forms can be available, it can be used in many medical applications such as hemostat, sealant, adhesion-prevention, wound care dressings with endoscope and DDS (Drug Delivery System).  

“Application of “LYDEX®”

We push forward the research and development of the applied technology using LYDEX® mainly in five domains.
Hemostat
Fibrin glue is widely used as hemostat in surgical operation where mechanical surgical treatment is effective for bleeding. But since fibrin glue is made from fibrinogen which is blood product, it has risk of infection such as virus.
As LYDEX® is made from natural material which is used for medical and food application, there is no risk of infection and it is being developed as hemostat substituting for fibrin glue.
Sealant for medical use
Fibrin glue is used not only as hemostat but also as sealant which prevent leakage of body fluid and air leakage from the lung. LYDEX®(powder type) is sprayed onto the biological tissue and then covered by sprayed water, becoming gel and adhering to tissue. In this process, LYDEX® shows strong sealing effect and it is being developed as novel medical sealant substituting for fibrin glue.
Adhesion prevention material for living tissue and organs
In surgical operation, undesired adhesion between operation wound and neighboring organs occurs at the rate of more than 90%. Therefore adhesion prevention material is used. But presently available adhesion prevention material has issues such as too short degradation time, too weak adhesion with organs and poor usability with endoscope.
LYDEX® (powder type) possessing excellent safety and functionality make it possible to be used with endoscope by spraying it to the part of adhesion-prone with the addition of sprayed water, resulting to instant gelling and adhering to organs. Since absorption time in the system could be modified by changing composition rate, LYDEX® has been developed to substitute for the conventional products.
Wound care dressings with endoscope
Hemostasis for peptic ulcer hemorrhage with endoscope is categorized to hemostat spraying, mechanical hemostasis, drug-injection hemostasis and tissue solidification. Here hemostat spraying is the method of spraying hemostat to the bleeding part under the view of endoscope. And the hemostat generally used is thrombin, sodium alginate and epinephrine-added saline. This is the simplest but is said to be less effective than other methods.
Since “LYDEX®” has excellent functionality and simple usability, it is developed as a wound care dressings for ulcer with endoscope substituting for conventional drug.
DDS (Drug Delivery System)
“LYDEX®”, which has excellent safety and functionality, can be presented as sheet-form or disc-form as well as liquid and powder. And since its absorption time is controllable, it is developed as a DDS solution which can deliver the drug effect to the desired point.

“References to “LYDEX®”

LYDEX
Self-Degradable Bioadhesive. 2007, Key Engineering Materials, 342-343, 713
Low cytotoxic tissue adhesive based on oxidized dextran and epsilon-poly-l-lysine.  J Biomed Mater Res A. 2014 Aug;102(8):2511-20. doi: 10.1002/jbm.a.34923. Epub 2013 Aug 30.
Self-degradation of tissue adhesive based on oxidized dextran and poly-l-lysine Carbohydrate Polymers Volume 113, 26 November 2014, Pages 32?38
Dextran oxidized by a malaprade reaction shows main chain scission through a maillard reaction triggered by schiff base formation between aldehydes and amines. Journal of Polymer Science Part A: Polymer Chemistry / Volume 54, Issue 14. First published: 16 March 2016
Controlling the degradation of an oxidized dextran-based hydrogel independent of the mechanical properties. Carbohydr Polym. 2019 Jan 15;204:131-141. doi: 10.1016/j.carbpol.2018.09.081. Epub 2018 Oct 3.
Hemostat
Evaluation of Wound Closure and Antihemorrhagic Efficiency of Medical Adhesive Composed of Aldehyded Dextran and Poly(L-lysine). Biomaterials Research 15(3) : 129-135 (2011)
Hemostatic effect of new surgical glue in animal partial nephrectomy models.  Urology. 2013 May;81(5):1095-100. doi: 10.1016/j.urology.2013.01.002. Epub 2013 Feb 20.
The effective control of a bleeding injury using a medical adhesive containing batroxobin." Biomed Mater. 2014 Apr;9(2):025002. doi: 10.1088/1748-6041/9/2/025002. Epub 2014 Jan 31.
Sealant
Creation of a uniform pleural defect model for the study of lung sealants. J Thorac Cardiovasc Surg. 2007 Jul;134(1):145-51.
Development of new biodegradable hydrogel glue for preventing alveolar air leakage. J Thorac Cardiovasc Surg. 2007 Nov;134(5):1241-8.
Anti-adhesion material
Novel biodegradable powder for preventing postoperative pleural adhesion. J Surg Res. 2013 Jan;179(1):e13-9. doi: 10.1016/j.jss.2012.01.056. Epub 2012 Apr 1.
Novel powdered anti-adhesion material: preventing postoperative intra-abdominal adhesions in a rat model. Int J Med Sci. 2013;10(4):467-74. doi: 10.7150/ijms.5607. Epub 2013 Mar 5.
Novel biodegradable powder for preventing postoperative pleural adhesion. J Surg Res. 2013 Jan;179(1):e13-9. doi: 10.1016/j.jss.2012.01.056. Epub 2012 Apr 1.
Prevention of retrosternal adhesion by novel biocompatible glue derived from food additives. J Thorac Cardiovasc Surg. 2013 Nov;146(5):1232-8. doi: 10.1016/j.jtcvs.2013.02.001. Epub 2013 Apr 10.
Wound care dressings with endoscope
Efficacy of a novel endoscopically deliverable muco-adhesive hemostatic powder in an acute gastric bleeding porcine model. PLoS One. 2019 Jun 11;14(6):e0216829. doi: 10.1371/journal.pone.0216829. eCollection 2019.
Drug Delivery System
Topical application of a biodegradable disc with amiodarone for atrial fibrillation. Ann Thorac Surg. 2011 Mar;91(3):734-9. doi: 10.1016/j.athoracsur.2010.10.022.
Aldehyded Dextran and ε-Poly(L-lysine) Hydrogel as Nonviral Gene Carrier. Stem Cells Int. 2013;2013:634379. doi: 10.1155/2013/634379. Epub 2013 Aug 21.
Scaffold
Biodegradable Adhesive (LYDEX) with Hydroxyapatite Granules. 2007, Key Engineering Materials, 361-363, 575
Development of a new tissue-engineered sheet for reconstruction of the stomach. Artif Organs. 2009 Oct;33(10):818-26. doi: 10.1111/j.1525-1594.2009.00808.x. Epub 2009 Oct 16.
Ophthalmology area
Sutureless amniotic membrane transplantation for ocular surface reconstruction with a chemically defined bioadhesive. Biomaterials. 2008 Jul;29(19):2923-31. doi: 10.1016/j.biomaterials.2008.03.027. Epub 2008 Apr 15.
Novel sutureless keratoplasty with a chemically defined bioadhesive. Invest Ophthalmol Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2679-85. doi: 10.1167/iovs.08-2944. Epub 2009 Jan 10.
An ex vivo model for suture-less amniotic membrane transplantation with a chemically defined bioadhesive.. Curr Eye Res. 2012 May;37(5):372-80. doi: 10.3109/02713683.2012.663853. Epub 2012 Mar 29.
Orthopedics area
Strong adhesiveness of a new biodegradable hydrogel glue, LYDEX, for use on articular cartilage. J Appl Biomater Funct Mater. 2013 Dec 16;11(3):e180-6. doi: 10.5301/JABFM.5000164.
Antibacterial
Sustained release of vancomycin from a new biodegradable glue to precent methicillin-resistant Ataphylococcus aureus graft ingection. Interact Cardiovasc Thorac Surg. 2010 Jul;11(1):52-5. doi: 10.1510/icvts.2010.232447. Epub 2010 Apr 1.
Antimicrobial effect of medical adhesive composed of aldehyded dextran and ε-Poly(L-Lysine). J Microbiol Biotechnol. 2011 Nov;21(11):1199-202.