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Hemostatic material

A technology of hemostatic materials and substrates, applied in the field of hemostatic materials, can solve the problem of small promotion of platelet aggregation

Active Publication Date: 2021-05-18
TORAY IND INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] On the one hand, it is known that lipid particles containing carboxylic acid type lipids, phospholipids and cholesterol, without H12 peptide on the surface, and lipid particles containing carboxylic acid type lipids, phospholipids and cholesterol, with H12 peptide on the surface, have Platelet aggregation-promoting effect, but lipid particles without H12 peptide on the surface have a smaller platelet aggregation-promoting effect than lipid particles having H12 peptide on the surface (Non-Patent Document 2)

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1~10 and comparative example 1

[0754] (1) Preparation of liposomes

[0755] Follow the steps below to prepare liposomes. At this time, the carboxylic acid-type lipid obtained by the above synthesis method was used together with the following lipids (commercially available). In addition, cholesterol may be described as "Chol" below.

[0756] DPPC (1,2-dipalmitoyl-sn-glycerol-3-phosphatidylcholine, manufactured by Nippon Seika Co., Ltd.)

[0757] DPPG (1,2-dipalmitoyl-sn-glycerol-3-phosphatidylglycerol, manufactured by NOF Sangyo Co., Ltd.)

[0758] DPPS (1,2-dipalmitoyl-sn-glycerol-3-phosphatidylserine, manufactured by NOF Sangyo Co., Ltd.)

[0759] Cholesterol (manufactured by Nippon Seika Co., Ltd.)

[0760] PEG-DSPE (1,2-distearoyl-sn-glycerol-3-phosphatidylethanolamine-N-[monomethoxypoly(ethylene glycol)], manufactured by NOF Corporation)

[0761] Lipids were mixed at the molar ratios shown in Table 1 to obtain lipid mixtures. The obtained lipid mixture was dissolved in tert-butanol, and the obta...

Embodiment 11 and 12

[0815] (1) Getting started with phospholipids

[0816] DPPA sodium salt (1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid sodium salt, 1,2-Dipalmitoyl-sn-glycero-3-phosphatidic acid, sodium salt) was purchased from NOF Sangyo Co., Ltd. ( COATSOME MA-6060LS). The -O-P(=O)(-OH)(-O - Na + ) into -P(=O)(-OH)(-OH) to produce acid-type DPPA. It should be noted that the solubility of anionic DPPA in tert-butanol is higher than that of DPPA sodium salt.

[0817] After mixing 150 mg of DPPA sodium salt and 15 mL of a mixed solution of chloroform and methanol (volume of chloroform:volume of methanol=6:4), 56.0 μL of 4M hydrochloric acid was added, and ultrasonic treatment was performed at 50° C. for 30 minutes. After sonication, the solvent was evaporated, 5 mL of tert-butanol was added, and NaCl was removed by filtration with a filter to obtain acid-form DPPA. It should be noted that the acid form of DPPA is obtained by reacting DPPA sodium salt with equimolar hydrochloric acid.

...

Embodiment 13~16

[0825] (1) Lipid synthesis

[0826] DHSG was synthesized in the same manner as above, and Asp-DHSG, Glu-DHSG, and AG-DHSG were synthesized in the same manner as above using the synthesized DHSG.

[0827] (2) Production of hemostatic materials

[0828] DHSG, Asp-DHSG, Glu-DHSG, and AG-DHSG were prepared in the same manner as above. In the same manner as above, a base material composite with a cellulose sponge and a poly-L-lactic acid resin fiber sheet formed on the cellulose sponge was produced, and the produced base material composite was punched out with a metal punch to obtain a diameter It is a 13mm cylindrical substrate complex. 66.7 μL each of 30 mg / mL DHSG, Asp-DHSG, Glu-DHSG, and AG-DHSG tert-butanol solutions were sprayed on the substrate part (fiber sheet part) of the obtained cylindrical substrate composite, and dried, thereby Make hemostatic material. In Example 13, a tert-butanol solution of DHSG was used to make a hemostatic material (hereinafter referred to a...

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Abstract

The purpose of the present invention is to provide a lipid-containing hemostatic material capable of promoting adhesion or agglutination of platelets even without having a protein or a peptide supported thereon, such as GPIb and H12, involved in for adhesion or agglutination of platelets. In order to accomplish said purpose, provided is a hemostatic material (10) provided with a water-insoluble base material (1) and a lipid supported on the surface of the base material (1), wherein the lipid comprises one or more types of anionic lipid.

Description

technical field [0001] The present invention relates to hemostatic materials. Background technique [0002] Platelets play a key role in hemostasis, and adhesion of blood platelets to blood vessels or aggregation of blood platelets are important opportunities for hemostasis. Many attempts have been made to artificially produce simulated platelets (platelet substitutes) in order to compensate for decreased platelet count or platelet dysfunction, or to cope with massive bleeding. As such platelet substitutes, for example, attempts have been made to carry proteins that exist on the surface of platelet membranes and are involved in adhesion to the blood vessel wall or aggregation of platelets, proteins that mediate the aggregation of platelets, or as these Lipid microparticles of peptides in active sites of proteins. The key role of platelet adhesion or aggregation is the glycoprotein GPIb present on the membrane surface and the von Willebrand factor (vWF) line as a plasma pro...

Claims

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Application Information

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IPC IPC(8): A61L15/20A61K9/127A61K9/107A61K9/70A61K31/225A61K47/24A61K47/28A61K47/34A61K47/36A61P7/04A61L15/26A61L15/28A61L15/42A61L15/64
CPCA61K47/28A61K9/1271A61L2400/04A61L24/0036A61L24/10A61K47/6911A61K47/542A61L24/08A61K31/23A61L24/046A61L24/0015A61L2300/22
Inventor 武冈真司中原景子西浦卫大坪真也车谷元荒金彻武田昌信中原诚小山久美
Owner TORAY IND INC
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