WO2016076744A1 - Composition pharmaceutique à effet hémostatique et cicatrisant - Google Patents

Composition pharmaceutique à effet hémostatique et cicatrisant Download PDF

Info

Publication number
WO2016076744A1
WO2016076744A1 PCT/RU2014/000860 RU2014000860W WO2016076744A1 WO 2016076744 A1 WO2016076744 A1 WO 2016076744A1 RU 2014000860 W RU2014000860 W RU 2014000860W WO 2016076744 A1 WO2016076744 A1 WO 2016076744A1
Authority
WO
WIPO (PCT)
Prior art keywords
cellulose
composition
wounds
wound
starch
Prior art date
Application number
PCT/RU2014/000860
Other languages
English (en)
Russian (ru)
Inventor
Борис Славинович ФАРБЕР
Артур Викторович МАРТЫНОВ
Софья Борисовна ФАРБЕР
Дмитрий Александрович МАНЫЧ
Original Assignee
Борис Славинович ФАРБЕР
Артур Викторович МАРТЫНОВ
Софья Борисовна ФАРБЕР
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Борис Славинович ФАРБЕР, Артур Викторович МАРТЫНОВ, Софья Борисовна ФАРБЕР filed Critical Борис Славинович ФАРБЕР
Priority to EA201700004A priority Critical patent/EA033876B1/ru
Priority to PCT/RU2014/000860 priority patent/WO2016076744A1/fr
Publication of WO2016076744A1 publication Critical patent/WO2016076744A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/717—Celluloses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/718—Starch or degraded starch, e.g. amylose, amylopectin

Definitions

  • the invention relates to pharmacy and urgent medicine, surgery, and in particular to topically applied powder compositions for quickly stopping bleeding in humans and animals.
  • a pharmaceutical composition with a hemostatic effect is a mixture of several substances, including several biological active hemostatic and wound healing, as well as several auxiliary and form-forming substances in the form of a sterile powder for topical use, which can also be used to accelerate wound healing, stop bleeding both with capillary, venous and arterial bleeding due to the ability to quickly swell in the wound and tampon it.
  • An analogue of the proposed drug is the drug “Celox” (Celox), which is able to absorb blood from the wound and turn into a gel, thereby closing open bleeding.
  • carboxylation carboxycellulose or carboxy starch
  • maleic, succinic, phthalic and other anhydrides of di- and poly-carboxylic acids can be used, and for alkylation, substances such as monochloroacetic acid (carboxymethyl cellulose or carboxymethyl starch are formed in this case).
  • Cellulose is one of the most common natural polymers. polysaccharide nature, the main component of the cell walls of plants, which determines the mechanical strength and elasticity of plant tissues.
  • Cellulose macromolecules are constructed from D-glucose units linked by 1, 4-beta-glycosidic bonds into linear unbranched chains. The average degree of polymerization of cellulose (the number of glycosidic residues) varies over a wide range - from several hundred (for viscose fiber pulp it is 300-500) to 10-14 thousand (for cotton fiber and bast fibers).
  • Cellulose has a complex supramolecular structure.
  • the primary element is a microfibril, consisting of several hundred macromolecules and having the form of a spiral (thickness 35-100, length 500-600 nm and above).
  • Carboxypropyl cellulose is a CPC, a cellulose derivative in which carboxylation of cellulose is carried out by introducing a carboxypropyl group (- CH 2 —CH 2 —CH 2 —COOH) through a covalent bond with the hydroxyl groups of glucose monomers. It is used in tablet coatings and as a prolonging excipient in the production of various dosage forms of drugs.
  • Carboxymethyl starch- is a modified starch, ether starch, water-soluble anionic polymer. It is odorless, non-toxic, linear in form with a degree of substitution of more than 0.2 or more soluble in water.
  • Epsilon-aminocaproic acid- (6-aminohexanoic acid or ⁇ -aminocaproic acid) is a hemostatic drug that inhibits the conversion of profibrinolysin to fibrinolysin.
  • Epsilon-acetyl-aminocaproic acid-acetyl-6-aminocaproic acid in the form of the sodium salt is used as a medicine called acetamine.
  • a feature of the action of Acemine is the ability to cleanse wounds from necrotic masses, reduce exudation, accelerate epithelization and tissue regeneration. Acemin is used to treat long-term non-healing wounds, burns, as well as for closed fractures, especially with prolonged bone non-healing, to accelerate the formation of a postoperative scar.
  • protamine is a low molecular weight (4-12 kD) basic nuclear protein; in many animals, along with histones, it is contained in sperm, and in some (for example, in fish) it completely replaces histones; the presence of protamine protects DNA from the action of nucleases and gives chromatin a compact form. It is an antagonist of heparin and enhances blood coagulation.
  • Activators of accumulation of cyclic adenosine monophosphate - substances that increase the accumulation of cyclic adenosine monophosphate (cAMP) in the cell are activators of adenylate cyclase (papaverine, bendazole) or phosphodiesterase inhibitors (dipyridamole).
  • Cyclic adenosine monophosphate is a secondary messenger of cells involved in conducting intracellular signals.
  • the adenosine 3,5- (phosphate) molecule is formed as a result of the action of adenylate cyclase (APC) on adenosine triphosphate.
  • APC adenylate cyclase
  • the main element of the cyclase system is adenylate cyclase, which is associated with the cell membrane and forms the receptor-G-proteinLZTR: ACC complex. G-proteins interact with ACC.
  • cAMP-dependent protein kinases A1 and A2
  • the concentration of cAMP in the cAMP cell is a key factor in the negative regulation of the function of ICC, activates protein kinase A is stored as “secondary messengers” when exposed to stimulants on the cell - cytokines, hormones, mitogens and antigens.
  • cAMP-dependent protein kinases A1 and A2
  • activates protein kinase A is stored as “secondary messengers” when exposed to stimulants on the cell - cytokines, hormones, mitogens and antigens.
  • With an increased content of cAMP in mast cells their response to signals causing degranulation weakens.
  • cAMP has a positive effect on the maturation and differentiation of macrophages, on their cytotoxic activity.
  • the activity of the cAMP signaling pathway regulates the expression of c-fos and c-jun genes, factor AP-1, the conduct of co-stimulatory signals by increasing the activity of transcription factors CREB, CREM, ATF.
  • the negative regulation of the cAMP-dependent signaling pathway is carried out by the enzyme phosphodiesterase, which destroys cAMP. Phosphodiesterases of the 3rd and 4th types function in lymphocytes.
  • cellulose Due to the presence of hydroxyl groups in elementary macromolecules, cellulose is easily esterified and alkylated; these reactions are widely used in industry to produce cellulose ethers and esters. Many cellulose derivatives are capable of forming elastic films, which determines their use in the production of various medicines.
  • MCA cellulose acetate membranes
  • Ultracellulose membranes pore size from 5 to 50 nm
  • Microfiltration membranes pore sizes from 100 to 1000 nm are used in microbiological, biological and physico-chemical analyzes, for cleaning microorganism solutions of drugs, sterilizing filtration, electrophoretic separation of blood serum proteins and other high molecular weight compounds.
  • cellulose acetate (AC) for microencapsulation of low and high molecular weight drugs is promising.
  • polymer microcapsules are of the order of tens or hundreds of microns, and the membrane thickness is hundredths or tenths of a micron.
  • Microencapsulated drugs are introduced into ointment bases, used to prepare syrups and other liquid dosage forms. Microencapsulation is used in the preparation of injectable mixtures in the form of suspensions of microcapsules for intramuscular and subcutaneous administration with controlled release.
  • cellulose acetate for microencapsulation of drugs allowed to obtain microcapsules with a release rate of the drug, depending on the size of the microcapsule.
  • Cellulose acetates are used as a polymer permeable membrane for the immobilization of enzymes (glucooxidase, invertase, esterase, etc.), as well as polyenzyme systems (glucose oxidase and catalase, glucose oxidase and peroxidase). Using cellulose triacetate, fibrous immobilized enzymes were obtained.
  • AC is used to create a film that protects the medicinal substance from the effects of the external environment, and also as a binding and granulating substance.
  • Water-soluble AC is used to coat tablets of various drugs (glucose, terpinghydrate, aspen, ascofen, amidopyrine, etc.) and serves as a protective coating, providing a prolonged effect of the drug substance.
  • methyl cellulose allow it to be used as a protective coating for medicinal substances for enteral or topical use.
  • MC methyl cellulose
  • MGPC methylhydroxypropylcellulose
  • Phthalyl, acetal cephthalyl, acetylsushchinil - cellulose derivatives are widely used in the manufacture of medicines.
  • Sodium salt of carboxymethyl cellulose can be used as a protective shell for suppositories intended for use in places with a hot climate. Tablets with good appearance and satisfactory characteristics for strength and disintegration in the body are usually obtained using (1-8)% Na-CMC solutions.
  • the CMC aluminum salt in the form of a 1-5% aqueous solution is used for the manufacture of rapidly disintegrating vaginal tablets.
  • Films of Na-CMC have a pronounced stimulating effect on reparative processes in infected skin wounds, accelerate the formation and maturation of granulation tissue, and actively influence fibrillogenesis processes.
  • An effective remedy for the treatment of long-term non-healing radiation burns is an ointment, which is a Na-CMC gel containing an anti-inflammatory substance - fodomos.
  • Ointments based on Na-CMC are used as light-protective, coating and cooling pastes.
  • Bactericidal fluids containing Na-CMC form water-washable films and can be used to treat external wounds.
  • Pure methyl cellulose hydrogels are used as a drying ointment or wet dressing, as well as protective ointments when working with organic solvents and aggressive media.
  • MC-based ointments containing anesthetics, antibiotics, silver salts, mercury, zinc, etc. are used.
  • MCC monocarboxycellulose
  • This form of MCC can be considered as a biomaterial that combines the properties of a wound cover and a therapeutic agent that stimulates healing.
  • the acceleration of healing of burns with the help of MCC is 35%.
  • the range of therapeutic effects of the suspension can be significantly expanded due to the introduction of biologically active substances.
  • the prolonged action of drugs can also be achieved by attaching them to the polymer matrix with a relatively labile covalent bond, in particular ester or amide.
  • the drug fixation reaction is carried out with carboxymethyl cellulose chloride.
  • Starches can be modified in several ways in order to change their technological and physico-chemical properties.
  • dextrins When heated with acid or as a result of enzymatic hydrolysis, long starch chains break down into simpler molecules with the formation of low molecular weight water-soluble dextrins (dextrin, polydextrin and maltodextrin). Dextrins can be cross stitched so that the chains form a loop. Cyclodextrins are substances used as solubilizers of hormones and fat-soluble vitamins.
  • Starches pregluteinize (pre-gelatinized) by high temperature extrusion to obtain instant gelatinization preparation.
  • Known oxidized starch obtained in reaction with sodium hypochlorite, characterized by the formation of transparent and low viscosity solutions.
  • the introduction of a carboxymethyl group makes starch less prone to degradation at high temperature and by bacteria.
  • Carboxymethylated starch is also called starch glycolate.
  • Carboxymethyl groups increase the wettability and solubility of starch; therefore, it is often used as a disintegrant of tablet dosage forms.
  • the disadvantage of this invention is the presence of expensive fibrinogen protein from donated blood in a lyophilized form.
  • chitosan and its salts have a very limited degree of swelling and the onset of action.
  • Such compositions cannot be used to urgently stop heavy gunshots, including abdominal bleeding due to the onset of action after 15-20 minutes. After this period of time with arterial bleeding, the patient loses more than 50% of the blood and dies.
  • these compositions are not able to activate tissue regeneration, like cAMP activators.
  • the aim of the invention is the creation of a pharmaceutical composition with a hemostatic and wound healing effect, capable of exerting a quick effect in emergency cases with rupture of blood vessels, including gunshot and including with arterial bleeding with topical application in the form of a sterile powder.
  • the goal is achieved by creating a pharmaceutical composition in the form of a sterile powder for topical use with a hemostatic and wound healing effect containing, as the main active ingredient, a carboxylated derivative of the glucopyranose polymer in the form of a salt with an amino acid (aminocaproic or acetylaminocaproic), peptide (protamine) and activators of cyclic adenosine monophosphate accumulation (papaverine, dipyridamole om).
  • a pharmaceutical composition in the form of a sterile powder for topical use with a hemostatic and wound healing effect containing, as the main active ingredient, a carboxylated derivative of the glucopyranose polymer in the form of a salt with an amino acid (aminocaproic or acetylaminocaproic), peptide (protamine) and activators of cyclic adenosine monophosphate accumulation (papaverine, dipyridamole om).
  • carboxymethyl cellulose or carboxypropyl cellulose, or succinyl cellulose, or carboxymethyl starch, or succinyl starch, or a mixture of carboxymethyl cellulose, carboxypropyl cellulose, succinyl cellulose, carbocyl, are used as the carboxylated derivative of the glucopyranose polymer;
  • epsilon-aminocaproic acid or acetyl-epsilon-aminocaproic acid, or a mixture of epsilon-aminocaproic acid and acetyl-epsilon-aminocaproic acid are used as the amino acid;
  • the protamine base is used as a peptide
  • carboxy starch for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof
  • carboxy starch for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof
  • epsilon-acetyl-aminocaproic acid for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof
  • protamine 0.1-5 are added kg of papaverine, 0.1-5 kg of bendazole, 0.1-5 kg of dipyridamole, mix until completely homogeneous, pack 1-30 g in aluminum bags or glass vials.
  • the bottles are corked with rubber stoppers and rolled with aluminum caps, and the aluminum bags are sealed on a packaging machine. Vials and bags are autoclaved under standard sterilization conditions (120 ° C, 30 min).
  • 0.1-90 kg of carboxycellulose for example, succinyl cellulose, maleinyl cellulose, carboxymethyl cellulose or a mixture thereof
  • carboxycellulose for example, succinyl cellulose, maleinyl cellulose, carboxymethyl cellulose or a mixture thereof
  • 0.1-30 kg of epsilon-aminocaproic acid 0.1-1 kg of protamine
  • 0.1-5 kg of papaverine are added
  • 0.1-5 kg of bendazole 0.1-5 kg of dipyridamole
  • mix until completely homogeneous pack 1-30 g in aluminum bags or glass vials.
  • the bottles are corked with rubber stoppers and rolled with aluminum caps, and the aluminum bags are sealed on a packaging machine. Vials and bags are sterilized in an autoclave under standard sterilization conditions (120 0 C, 30 min).
  • 0.1-90 kg of carboxycellulose for example, succinyl cellulose, maleinyl cellulose, carboxymethyl cellulose or a mixture thereof
  • carboxy starch for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof
  • 0.1-30 kg of epsilon-aminocaproic acid for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof
  • 0.1-30 kg of epsilon-aminocaproic acid for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof
  • 0.1-30 kg of epsilon-aminocaproic acid for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof
  • 0.1-30 kg of epsilon-aminocaproic acid for example, succinyl starch, maleinyl starch, carboxymethyl starch or
  • Example 4 The effect of the drug "Carbox” and “Gemma” on the coagulation time
  • Example 5 The rate of resorption "Carbox” and “Gemma”
  • Materials for the study were hemostatic application tools: hemostatic collagen sponge, Cellox, Gemostop, as well as new materials on Carbox and Gemma.
  • the study was carried out in vitro under experimental conditions: a sample of hemostatic material weighing 1 g was placed in a volumetric tube containing 5 ml of distilled water. The tube was placed in a thermostat with a constant temperature of 37 °.
  • the results of the biological degradation rate of each hemostatic material were evaluated on days 1, 3, 7, and 14.
  • the test hemostatic tube was removed from the thermostat and a visual descriptive evaluation of the hemostatic agent was performed.
  • the studied hemostop was removed from the experimental medium and dried. Subsequently, repeated weighing of the studied hemostop was performed. The difference in the mass of the hemostop before the experimental study and after its implementation, expressed as a percentage, reflected the rate of resorption of the studied drug. Studying in an experiment in vitro the rate of degradation of hemostatic agents showed that all the studied samples of materials were resorbed.
  • hygroscopicity - volume (mass) of water absorbed by the material (ml); t 2 - mass (g) of material.
  • SP sorption indicator
  • the data obtained were processed statistically with the calculation of average values, average errors of the means and the significance of differences using the Student and Mann-Whitney criteria (with respect to the hemostatic collagen sponge).
  • the error of the statistical hypothesis was p ⁇ 0.05.
  • a relatively high sorption activity was demonstrated by a hemostatic collagen sponge having hygroscopicity of 69.41 ⁇ 1.65 ml / g and a sorption index of 15.1 ⁇ 0.95 mlhc / g.
  • the results of the hygroscopicity of the Carbox and Gemma materials were 70.31 ⁇ 1, 71 ml / g (p ⁇ 0.05) and 49.1 ⁇ 0.31 ml / g (p ⁇ 0.05), and sorption the indicator is 17.4 ⁇ 1, 11 mlkhs / g (p ⁇ 0.05) and 11.7 ⁇ 1, 12 mlkhs / g (p ⁇ 0.05), respectively.
  • the minimum sorption properties were noted in the hemostops “Celox” and “Hemostop”, the hygroscopicity of which amounted to 5.63 ⁇ 1.21 ml / g and 6.11 ⁇ 1.16 ml / g, and the sorption index was 1.23 ⁇ 0.11 mlhs / g and 1, 10 ⁇ 0.04 mlhs / g, respectively.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne une composition pharmaceutique sous forme d'une poudre stérile à administration percutanée avec effet hémostatique et cicatrisant comprenant en tant que substance active principale un dérivé carboxylé de polymère glucopyranose sous forme de sel avec un acide aminé (aminocaproïque ou acétylaminocaproïque), un peptide (protamine) et des activateurs d'accumulation d'adénosine-monophosphate (papavérine, bendazole ou dipyridamole). La composition peut être utilisée pour stopper rapidement les saignements veineux ou artériels d'origine traumatique (blessures par armes à feu,etc.) et l'activation de la régénération de blessures, y compris post-opératoires, cavitaires, traumatiques, y.c. les blessures par armes à feu). Le domaine d'utilisation sont la pharmacie, la chirurgie, la médecine en cas de catastrophes et les premiers soins.
PCT/RU2014/000860 2014-11-13 2014-11-13 Composition pharmaceutique à effet hémostatique et cicatrisant WO2016076744A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EA201700004A EA033876B1 (ru) 2014-11-13 2014-11-13 Фармацевтическая композиция с гемостатическим и ранозаживляющим действием
PCT/RU2014/000860 WO2016076744A1 (fr) 2014-11-13 2014-11-13 Composition pharmaceutique à effet hémostatique et cicatrisant

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/RU2014/000860 WO2016076744A1 (fr) 2014-11-13 2014-11-13 Composition pharmaceutique à effet hémostatique et cicatrisant

Publications (1)

Publication Number Publication Date
WO2016076744A1 true WO2016076744A1 (fr) 2016-05-19

Family

ID=55954702

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU2014/000860 WO2016076744A1 (fr) 2014-11-13 2014-11-13 Composition pharmaceutique à effet hémostatique et cicatrisant

Country Status (2)

Country Link
EA (1) EA033876B1 (fr)
WO (1) WO2016076744A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3524323A4 (fr) * 2016-10-05 2020-05-27 Maruha Nichiro Corporation Agent de cicatrisation des plaies ayant pour effet de renforcer les propriétés antibactériennes et les propriétés de cicatrisation des plaies

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4405324A (en) * 1981-08-24 1983-09-20 Morca, Inc. Absorbent cellulosic structures
US8575132B2 (en) * 2007-08-09 2013-11-05 Xin Ji Modified starch material of biocompatible hemostasis

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4405324A (en) * 1981-08-24 1983-09-20 Morca, Inc. Absorbent cellulosic structures
US8575132B2 (en) * 2007-08-09 2013-11-05 Xin Ji Modified starch material of biocompatible hemostasis

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
"Aminokapronovaia kislota (Aminocaproic acid): instruktsiia, primenenie i formula.", ENTSIKLOPEDIIA LEKARSTV I TOVAROV APTECHNOGO ASSORTIMENTA, 2007, Retrieved from the Internet <URL:http://www.rlsnet.ru/mnn_index_id_350.htm> [retrieved on 20150717] *
"Atseksamovaia kislota (Acexamic acid): instruktsiia, primenenie i formula.", ENTSIKLOPEDIIA LEKARSTV I TOVAROV APTECHNOGO ASSORTIMENTA, 2005, [retrieved on 20150717] *
"Bendazol (Bendazol): instruktsiia, primenenie i the claims.", ENTSIKLOPEDIIA LEKARSTV I TOVAROV APTECHNOGO ASSORTIMENTA (ELEKTRONNAIA VERSIIA, Retrieved from the Internet <URL:http://www.rlsnet.ru/mnn_index_id_42.htm> [retrieved on 20150717] *
"Dipiridamol (Dipyridamole: instruktsiia, primenenie i formula.", ENTSIKLOPEDIIA LEKARSTV I TOVAROV APTECHNOGO ASSORTIMENTA, 2011, Retrieved from the Internet <URL:http://www.rlsnetru/mnn_index_id_829.htm> [retrieved on 20150717] *
"Protamina sulfat (Protamine sulfate): instruktsiia, primenenie i formula.", ENTSIKLOPEDIIA LEKARSTV I TOVAROV APTECHNOGO ASSORTIMENTA, 1999, Retrieved from the Internet <URL:http://www.rlsnet.ru/mnn_index_id_2026.htm> [retrieved on 20150717] *
"Sosudorasshiriaiuschie sredstva.", BOLSHAIA SOVETSKAIA ENTSIKLOPEDIIA. M., SOVETSKAIA ENTSIKLOPEDIIA, 1996, Retrieved from the Internet <URL:http://dic.academic.ru/dic.nsf/bse/134626/Sosudorasshiriaiushchie> [retrieved on 20150717] *
A. S. TURAEV ET AL.: "«Gemostaticheskaia aktivnost i sposobnost k rassasyvaniiu karboksimetiltselliulozy»", KHIMIKO -FARMATSEVTICHESKII ZHURNAL, vol. 24, no. 8, 1990, Moscow, pages 47 - 50 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3524323A4 (fr) * 2016-10-05 2020-05-27 Maruha Nichiro Corporation Agent de cicatrisation des plaies ayant pour effet de renforcer les propriétés antibactériennes et les propriétés de cicatrisation des plaies

Also Published As

Publication number Publication date
EA201700004A1 (ru) 2017-08-31
EA033876B1 (ru) 2019-12-04

Similar Documents

Publication Publication Date Title
Liu et al. Preparation and characterization of chitosan–collagen peptide/oxidized konjac glucomannan hydrogel
US11229724B2 (en) Biocompatible and bioabsorbable derivatized chitosan compositions
EP3659631B1 (fr) Pansement comprenant de l&#39;acide hyaluronique-calcium et de la polylysine et procédé de fabrication s&#39;y rapportant
RU2369408C2 (ru) Гемостатическая композиция, включающая гиалуроновую кислоту
JP6069394B2 (ja) 医薬組成物
EP3034085A1 (fr) Médicament contenant du chitosane cationisé
US20140010887A1 (en) Modified starch material of biocompatible hemostasis
KR20170093243A (ko) 유동성 지혈 조성물
GB2344519A (en) Sterile therapeutic compositions
CN113577014B (zh) 医疗器械、水凝胶及其制备方法与应用
Abdelhak A review: Application of biopolymers in the pharmaceutical formulation
CN108421081A (zh) 一种抗感染、安全高效的止血气凝胶及其制备方法
Wang et al. Preparation and evaluation of chitosan-and hyaluronic acid-grafted pullulan succinate films for skin wound healing
CN105126153B (zh) 一种含有凝血酶的复合止血膜及其制备方法
WO2016076744A1 (fr) Composition pharmaceutique à effet hémostatique et cicatrisant
RU2657826C1 (ru) Композиция для получения гидрогеля
JP6877360B2 (ja) 止血組成物
EP2473203A2 (fr) Compositions et procédés destinés à désinfecter des matériaux
RU2315599C2 (ru) Способ получения лекарственной мембраны
RU2767853C1 (ru) Комплексное соединение иона Co2+ и полиакриловой кислоты, обладающее гемостатическими, антимикробными и ранозаживляющими свойствами
Pluta et al. Properties and active substance release kinetics from gelatin-alginate matrices
Evranos The Synthesis of Ph-responsıve Polymeric Film wıth an Enhanced Mechanical Properties for Wound Dress Applications
RU50416U1 (ru) Лекарственная мембрана
Lee et al. Genotoxicity Study of Carboxymethyl Chitosan-based Hydrogel for Clinical Use
CN114832148A (zh) 一种具有抗菌消炎功能的止血材料及制备方法与用途

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14905943

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 201700004

Country of ref document: EA

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14905943

Country of ref document: EP

Kind code of ref document: A1