US20150209481A1 - Antiadhesive Material - Google Patents
Antiadhesive Material Download PDFInfo
- Publication number
- US20150209481A1 US20150209481A1 US14/419,260 US201314419260A US2015209481A1 US 20150209481 A1 US20150209481 A1 US 20150209481A1 US 201314419260 A US201314419260 A US 201314419260A US 2015209481 A1 US2015209481 A1 US 2015209481A1
- Authority
- US
- United States
- Prior art keywords
- antiadhesive material
- poly
- cst
- glutamic acid
- adhesion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000463 material Substances 0.000 title claims abstract description 50
- 230000000181 anti-adherent effect Effects 0.000 title claims abstract description 46
- 239000004220 glutamic acid Substances 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 239000000843 powder Substances 0.000 claims abstract description 18
- 239000004615 ingredient Substances 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000012153 distilled water Substances 0.000 claims abstract description 8
- 210000000056 organ Anatomy 0.000 claims description 23
- 206010060932 Postoperative adhesion Diseases 0.000 claims description 13
- 238000001356 surgical procedure Methods 0.000 abstract description 11
- 238000002674 endoscopic surgery Methods 0.000 abstract description 9
- 230000000052 comparative effect Effects 0.000 description 13
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 12
- 210000003815 abdominal wall Anatomy 0.000 description 12
- 229910052708 sodium Inorganic materials 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 206010052428 Wound Diseases 0.000 description 11
- 208000027418 Wounds and injury Diseases 0.000 description 11
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- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 206010000050 Abdominal adhesions Diseases 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
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- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
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- 229920001202 Inulin Polymers 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
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- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 229940051593 dermatan sulfate Drugs 0.000 description 1
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- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 208000003243 intestinal obstruction Diseases 0.000 description 1
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 1
- 229940029339 inulin Drugs 0.000 description 1
- KXCLCNHUUKTANI-RBIYJLQWSA-N keratan Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@H](COS(O)(=O)=O)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@H](O[C@@H](O[C@H]3[C@H]([C@@H](COS(O)(=O)=O)O[C@@H](O)[C@@H]3O)O)[C@H](NC(C)=O)[C@H]2O)COS(O)(=O)=O)O[C@H](COS(O)(=O)=O)[C@@H]1O KXCLCNHUUKTANI-RBIYJLQWSA-N 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/047—Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/145—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/424—Anti-adhesion agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Definitions
- the present invention relates to an antiadhesive material, and more particularly relates to an antiadhesive material that provides high safety and favorable handleability on the surgery.
- postoperative adhesions cause, for example, infertility due to fallopian tube adhesions, intestinal obstruction due to intestinal adhesions, and the like, and require a second surgery, which imposes a heavy burden on patients. Furthermore, the second surgery may even cause additional damage to the organs as a result of dissection of the adhesion site.
- an antiadhesive material in film form is known with which a wound site is physically covered on the surgery.
- Patent Document 1 WO 2006/054624
- Patent Document 2 WO 2007/132785
- the present invention has been made to solve the above-described problems, and it is an object thereof to provide an antiadhesive material that is easy to handle even when applied to a case such as endoscopic surgery and that can effectively prevent postoperative adhesion of organs in a wound site.
- the present invention provides an antiadhesive material containing a poly- ⁇ -glutamic acid having a weight-average molecular weight of 600,000 to 13,000,000 and/or a salt thereof as an effective ingredient.
- the poly- ⁇ -glutamic acid and/or a salt thereof has a kinematic viscosity at 37° C. of 2 cSt to 15 cSt when dissolved in distilled water at a concentration of 0.05% by mass.
- the antiadhesive material is processed into powder or gel form.
- the antiadhesive material is used to prevent postoperative adhesion of an organ in a wound site.
- the present invention also provides an antiadhesive material containing a poly- ⁇ -glutamic acid having a kinematic viscosity at 37° C. of 2 cSt to 15 cSt when dissolved in distilled water at a concentration of 0.05% by mass and/or a salt thereof as an effective ingredient.
- the poly- ⁇ -glutamic acid has a weight-average molecular weight of 600,000 to 13,000,000 and/or a salt thereof.
- the antiadhesive material is processed into powder or gel form.
- the antiadhesive material is used to prevent postoperative adhesion of an organ in a wound site.
- the present invention it is possible to provide an antiadhesive material that can effectively prevent postoperative adhesion of organs in a wound site and that is easy to handle even in relatively localized surgery such as endoscopic surgery. Moreover, the antiadhesive material of the present invention does not essentially require the use of ingredients derived from living organisms, and therefore confirmation of the safety in relation to contamination with infectious agents as strictly required for formulations derived from living organisms is not necessary. Furthermore, there is no need for crosslinking treatment, and it is therefore possible to solve the problems in manufacturing, such as the control of the degree of crosslinking.
- An antiadhesive material of the present invention contains poly- ⁇ -glutamic acid and/or a salt thereof as an effective ingredient.
- poly- ⁇ -glutamic acid is a linear polymer of glutamic acid bound by peptide linkages between y-carboxyl and a-amino groups.
- An example of the salt of poly- ⁇ -glutamic acid is sodium poly- ⁇ -glutamate.
- the poly- ⁇ -glutamic acid and/or a salt thereof that is used in the present invention is uncrosslinked.
- the poly- ⁇ -glutamic acid and/or a salt thereof in the present invention has a weight-average molecular weight of, for example, 600,000 to 13,000,000, preferably 800,000 to 10,000,000. If the weight-average molecular weight of the poly- ⁇ -glutamic acid and/or a salt thereof is less than 600,000, even when the material is applied to an affected part of a subject in order to prevent adhesion, the material may not appropriately stay in that affected part due to insufficient viscosity and thus allow the progression of adhesion between the surface of an organ and surrounding tissues without sufficiently exercising appropriate physical barrier functions for the affected part.
- weight-average molecular weight there is no particular limitation on the upper limit of the weight-average molecular weight, but it is considered that a poly- ⁇ -glutamic acid having a molecular weight exceeding 13,000,000 and/or a salt thereof would be difficult to manufacture using a conventionally known method of manufacturing.
- the poly- ⁇ -glutamic acid and/or a salt thereof in the present invention is a polymer having a kinematic viscosity at 37° C. of, for example, 2 cSt to 15 cSt and preferably 2.5 cSt to 8 cSt when dissolved in distilled water at a concentration of 0.05% by mass.
- the kinematic viscosity of the poly- ⁇ -glutamic acid and/or a salt thereof is less than 2 cSt, even when the material is applied to an affected part of a subject in order to prevent adhesion, the material may not stay in that affected part due to insufficient viscosity and thus allow the progression of adhesion between the surface of an organ and surrounding tissues without sufficiently exercising appropriate physical barrier functions for the affected part.
- There is no particular limitation on the upper limit of the kinematic viscosity but it is considered that a poly- ⁇ -glutamic acid having a kinematic viscosity exceeding 15 cSt and/or a salt thereof would be difficult to manufacture using a conventionally known method of manufacturing.
- the poly- ⁇ -glutamic acid and/or a salt thereof, which is contained as the effective ingredient satisfies either of the above-described range of weight-average molecular weight or the above-described range of kinematic viscosity under the predetermined conditions, or both.
- Examples of the poly- ⁇ -glutamic acid and a salt thereof as described above include those conventionally designated as food additives. Therefore, the safety for living organisms including human bodies has already been ensured.
- the poly- ⁇ -glutamic acid or a salt thereof satisfying either of the above-described predetermined range of weight-average molecular weight or the predetermined range of kinematic viscosity, or both that composes the antiadhesive material of the present invention can be easily produced by a person skilled in the art from, for example, a Bacillus microorganism such as Bacillus subtilis by using, for example, a method described in Biosci. Biotech., 56, 1031-1035 (1992).
- the antiadhesive material of the present invention may also contain other ingredient that is effective in preventing adhesion, other ingredient that is effective in retaining a given form, a molecularly targeted drug that targets for a molecule related to adhesion formation, and the like without interfering with the adhesion preventing ability that the poly- ⁇ -glutamic acid or a salt thereof itself has.
- Examples of the other ingredient that is effective in preventing adhesion include, but not limited to, commonly-used polysaccharides such as amylose, amylopectin, inulin, dextran, dextrin, pectin, alginic acid, carboxymethyl cellulose, and the like; glycosaminoglycans such as hyaluronic acid, alginic acid, heparan sulfate, chondroitin sulfate, chondroitin, dermatan sulfate, keratosulfate, heparin, and the like; disaccharides such as trehalose and the like; alcohols such as glycerin and the like; and synthetic polymers such as polyethylene glycol and the like.
- commonly-used polysaccharides such as amylose, amylopectin, inulin, dextran, dextrin, pectin, alginic acid, carboxymethyl cellulose, and the like
- the form of the antiadhesive material of the present invention is not particularly limited, but may be a powder or a gel for the reasons that postoperative adhesion of organs in a wound site can be effectively prevented and that handling is easy even in an area of relatively localized surgery such as endoscopic surgery.
- a powder for example, a poly- ⁇ -glutamic acid and/or a salt thereof that is originally in powder form can be used as it is.
- a poly- ⁇ -glutamic acid and/or a salt thereof that is originally in gel form can be selected and used as it is, or a poly- ⁇ -glutamic acid and/or a salt thereof in powder form can be used after appropriate mixing with a biocompatible medium such as water, saline, or the like and processing into a gel form.
- a biocompatible medium such as water, saline, or the like
- processing into a gel form it is desirable that a person skilled in the art pays attention to the amount of medium that is used so as not to significantly increase the fluidity of the resultant antiadhesive material.
- the antiadhesive material processed into a gel form has excessively high fluidity, even when the antiadhesive material is applied to an affected part of a subject in order to prevent adhesion, the antiadhesive material may not stay in the affected part due to insufficient viscosity and thus allow the progression of adhesion between the surface of an organ and surrounding tissues without sufficiently exercising appropriate physical barrier functions for the affected part.
- the antiadhesive material of the present invention can be applied on the surgery by, for example, coating or spraying onto a wound site and the surfaces of organs located around the wound site or surrounding tissues.
- the application may be performed with a plurality of times coating or spraying onto a local portion of the surface of the target organ or surrounding tissues, or with coating or spraying onto the entire target surface at one time.
- a coating or spraying device may be used. The dose can be appropriately selected by a person skilled in the art.
- the antiadhesive material of the present invention can be applied, without limitation, to organs of humans and other mammals (e.g., laboratory animals, pets, or domestic animals, such as mice, rats, hamsters, rabbits, dogs, cats, cattle, swine, sheep, deer, wild boars, and the like).
- organs include digestive organs (stomach, small intestine, large intestine, and the like), genital organs (uterus, ovary, or the like), circulatory organs (heart, blood vessels, lymphatic vessels, and the like), respiratory organs (e.g., lung), locomotive organs (muscles, bones, ligaments, and the like), and sensory organs (eyeballs and the like).
- the antiadhesive material of the present invention can be effectively used in not only endoscopic surgery but also common surgery.
- kinematic viscosity (cSt) was measured using an Ubbelohde viscometer (manufactured by Sibata Scientific Technology Ltd., (model) SU-00286) at a sample temperature of 37° C.
- the kinematic viscosity was calculated by the following equation using the obtained efflux time (sec):
- Donryu rats male, 5 to 8 weeks old were divided into five groups, namely, Groups A, B, C, D, and E such that each group was composed of 4 to 8 rats.
- Each rat was subjected to laparotomy by abdominal midline incision under general anesthesia.
- the ileocecum of the large intestine was taken out of the abdominal cavity.
- the serosal surface thereof was rubbed with gauze until small bleeding spots appeared, and then exposed to warm air from a dryer for about 10 seconds.
- an about 1 cm ⁇ 1 cm area of the abdominal wall directly above the ileocecum of the the large intestine was excised, and the abdominal wall was exposed to warm air from a dryer for about 10 seconds, and then dried in room air for about 10 minutes.
- the rubbed portion of the ileocecum and the excision portion of the abdominal wall were coated with about 0.2 g of a sodium poly- ⁇ -glutamate powder having a weight-average molecular weight of 1,100,000 to 1,300,000 and a kinematic viscosity of 3.2 cSt to 3.5 cSt (PGA; Example 1) such that the entire surface of those portions was covered, and the abdomen was closed such that the rubbed portion of the ileocecum and the excision portion of the abdominal wall came into contact with each other.
- PGA kinematic viscosity
- the rubbed portion of the ileocecum and the excision portion of the abdominal wall were coated with about 0.2 g of a sodium poly- ⁇ -glutamate powder having a weight-average molecular weight of 9,800,000 and a kinematic viscosity of 7.7 cSt (PGA; Example 2) such that the entire surface of those portions was covered, and the abdomen was closed such that the rubbed portion of the ileocecum and the excision portion of the abdominal wall came into contact with each other.
- PGA kinematic viscosity
- the rubbed portion of the ileocecum and the excision portion of the abdominal wall were coated with about 0.2 g of a crosslinked poly- ⁇ -glutamic acid obtained by crosslinking poly- ⁇ -glutamic acid by gamma-irradiation (crosslinked PGA; Comparative Example 1) such that the entire surface of those portions was covered, and the abdomen was closed such that the rubbed portion of the ileocecum and the excision portion of the abdominal wall came into contact with each other.
- Example 2 Example 3 1 2 Group C Group D Group E Group A Group B (Cross- (Sepra- (No (PGA) (PGA) linked PGA) film) treatment) Score: 0 4 1 1 0 0 Score: 1 0 3 5 0 0 Score: 2 0 0 2 1 0 Score: 3 2 0 0 3 0 Score: 4 0 0 0 1 3 Score: 5 0 0 0 1 2 Average 1.0 ⁇ 1.5 0.8 ⁇ 0.5 1.1 ⁇ 0.6 3.3 ⁇ 1.0 4.4 ⁇ 0.5 Value Numerical values in the table show the number of individuals.
- Example 3 Three polystyrene (PSt) Petri dishes were prepared. Then, 20 mg each of a sodium poly- ⁇ -glutamate powder having a weight-average molecular weight of 800,000 and a kinematic viscosity of 2.8 cSt (Example 3), a sodium poly- ⁇ -glutamate powder having a weight-average molecular weight of 1,500,000 to 2,500,000 (catalog value) and a kinematic viscosity of 5.5 cSt (manufactured by Wako Pure Chemical Industries, Ltd.; Example 4), and a sodium poly- ⁇ -glutamate powder having a weight-average molecular weight of 200,000 to 500,000 (catalog value) and a kinematic viscosity of 1.1 cSt (manufactured by Wako Pure Chemical Industries, Ltd.; Comparative Example 4) were applied to the respective Petri dishes by coating. After that, 0.1 ml of distilled water was added to each Petri dish and mixed using
- the sodium poly- ⁇ -glutamate powder of Comparative Example 4 as having a weight-average molecular weight of less than 600,000 or a kinematic viscosity of less than 2 cSt, exhibited increased fluidity when gelled, and readily flowed when the Petri dish was tilted.
- the sodium poly- ⁇ -glutamate powders of Examples 3 and 4 having a weight-average molecular weight or a kinematic viscosity exceeding these ranges had a tendency of the gel to be likely to stay in place on the bottom surface of the Petri dish.
- the antiadhesive material of the present invention after being applied to an affected part of a subject has a tendency to stay in that affected part even when swelled with, for example, moisture etc. in the body of the subject and gelled, and thus can prevent the progression of adhesion between the surface of an organ and surrounding tissues by exercising appropriate physical barrier functions for the affected part.
- the antiadhesive material of the present invention may have any form such as powder or gel form, and therefore, for example, is easy to handle even in relatively localized surgery such as endoscopic surgery and can more reliably prevent adhesion.
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| JP2012-180332 | 2012-08-16 | ||
| JP2012180332 | 2012-08-16 | ||
| PCT/JP2013/069921 WO2014027545A1 (ja) | 2012-08-16 | 2013-07-23 | 癒着防止材 |
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| US15/715,210 Division US10744234B2 (en) | 2012-08-16 | 2017-09-26 | Method for preventing postoperative adhesion of an organ in a wound site |
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| US15/715,210 Expired - Fee Related US10744234B2 (en) | 2012-08-16 | 2017-09-26 | Method for preventing postoperative adhesion of an organ in a wound site |
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| US15/715,210 Expired - Fee Related US10744234B2 (en) | 2012-08-16 | 2017-09-26 | Method for preventing postoperative adhesion of an organ in a wound site |
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| US (2) | US20150209481A1 (enExample) |
| EP (1) | EP2839851A4 (enExample) |
| JP (1) | JP6225906B2 (enExample) |
| CN (1) | CN104379184A (enExample) |
| IN (1) | IN2014MN02651A (enExample) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10752733B2 (en) * | 2016-04-08 | 2020-08-25 | Idemitsu Kosan Co.,Ltd. | Binder for electrochemical element |
| US20230040901A1 (en) * | 2018-01-04 | 2023-02-09 | PlantTec Medical GmbH | Pharmaceutical composition for inhibiting postoperative adhesions |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107596456A (zh) * | 2017-10-11 | 2018-01-19 | 广州新诚生物科技有限公司 | 一种具有止血功能的生物医用膜及其制备方法 |
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| US20080118907A1 (en) * | 2004-11-18 | 2008-05-22 | Keio University | Adhesion-Preventing Material And Process For Preventing Adhesion |
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| JP3466318B2 (ja) * | 1994-03-22 | 2003-11-10 | 株式会社日本触媒 | 吸水剤組成物およびその製法、並びにこれら吸水剤組成物を含有する吸収物品 |
| JPH09296039A (ja) * | 1996-05-02 | 1997-11-18 | Eiweiss Kk | 活性化ポリ−l−グルタミン酸、これを用いた止血用・医療用接着キット、および該キットの使用方法 |
| JPH11276572A (ja) * | 1998-03-31 | 1999-10-12 | Kanegafuchi Chem Ind Co Ltd | ポリ(γ−グルタミン酸)塩複合体からなる医療材料 |
| US7364879B2 (en) * | 2003-12-19 | 2008-04-29 | Tung Hai Biotechnology Corporation | Stable biodegradable, high water absorbable polyglutamic acid hydrogel by 3-dimensional cross-linking and its preparation method |
| AU2006279218B2 (en) | 2005-08-11 | 2013-05-02 | Adetherapeutics, Inc. | Reducing post-operative adhesion formation with intraperitoneal glutamine |
| EP2025354A4 (en) * | 2006-05-16 | 2010-06-02 | Univ Keio | AGENT FOR THE PREVENTION OF ORGAN ADHESION AND METHOD FOR PREVENTING ADHESION THEREWITH |
| KR101125934B1 (ko) * | 2008-11-19 | 2012-03-21 | 한남대학교 산학협력단 | 열감응성 조직 유착 방지 조성물 및 이의 제조 방법 |
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- 2013-07-23 US US14/419,260 patent/US20150209481A1/en not_active Abandoned
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| US20080118907A1 (en) * | 2004-11-18 | 2008-05-22 | Keio University | Adhesion-Preventing Material And Process For Preventing Adhesion |
Non-Patent Citations (2)
| Title |
|---|
| Ho et al (Polyglutamic Acid Produced by Bacillus subtilis (natto): Structural characteristics, Chemical Properties and Biological Functionalities, Journal of the Chinese Chemical Society, 2006, 53, 1363-1384). * |
| Tsao et al (Evaluation of chitosan/γ-poly(glutamic acid) polyelectrolyte complex for wound dressing materials, Carbohydrate polymers, Vol. 84, Issue 2, March 2011, pages 812-819). * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10752733B2 (en) * | 2016-04-08 | 2020-08-25 | Idemitsu Kosan Co.,Ltd. | Binder for electrochemical element |
| US20230040901A1 (en) * | 2018-01-04 | 2023-02-09 | PlantTec Medical GmbH | Pharmaceutical composition for inhibiting postoperative adhesions |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104379184A (zh) | 2015-02-25 |
| WO2014027545A1 (ja) | 2014-02-20 |
| IN2014MN02651A (enExample) | 2015-08-21 |
| JP6225906B2 (ja) | 2017-11-08 |
| EP2839851A1 (en) | 2015-02-25 |
| JPWO2014027545A1 (ja) | 2016-07-25 |
| US20180015208A1 (en) | 2018-01-18 |
| EP2839851A4 (en) | 2015-11-25 |
| US10744234B2 (en) | 2020-08-18 |
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