EA023447B1 - Производное инсулина, обладающее сахароснижающей активностью при пероральном применении, способ его получения и лекарственные формы на его основе - Google Patents
Производное инсулина, обладающее сахароснижающей активностью при пероральном применении, способ его получения и лекарственные формы на его основе Download PDFInfo
- Publication number
- EA023447B1 EA023447B1 EA201300207A EA201300207A EA023447B1 EA 023447 B1 EA023447 B1 EA 023447B1 EA 201300207 A EA201300207 A EA 201300207A EA 201300207 A EA201300207 A EA 201300207A EA 023447 B1 EA023447 B1 EA 023447B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- insulin
- pharmaceutical composition
- composition according
- peptides
- oral administration
- Prior art date
Links
- 239000002552 dosage form Substances 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title abstract description 8
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 230000002058 anti-hyperglycaemic effect Effects 0.000 title abstract 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract description 97
- 102000004877 Insulin Human genes 0.000 claims abstract description 53
- 108090001061 Insulin Proteins 0.000 claims abstract description 53
- 229940125396 insulin Drugs 0.000 claims abstract description 47
- 108010038807 Oligopeptides Proteins 0.000 claims abstract description 8
- 102000015636 Oligopeptides Human genes 0.000 claims abstract description 8
- 230000007071 enzymatic hydrolysis Effects 0.000 claims abstract description 4
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 claims abstract description 4
- 230000002255 enzymatic effect Effects 0.000 claims abstract 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 108090000790 Enzymes Proteins 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 239000000443 aerosol Substances 0.000 claims description 4
- 229940088598 enzyme Drugs 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 102000004169 proteins and genes Human genes 0.000 claims description 3
- 108090000623 proteins and genes Proteins 0.000 claims description 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 2
- 108090000317 Chymotrypsin Proteins 0.000 claims description 2
- 108010067770 Endopeptidase K Proteins 0.000 claims description 2
- 108090000526 Papain Proteins 0.000 claims description 2
- 239000004365 Protease Substances 0.000 claims description 2
- 108090000631 Trypsin Proteins 0.000 claims description 2
- 102000004142 Trypsin Human genes 0.000 claims description 2
- 229960002376 chymotrypsin Drugs 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 229940055729 papain Drugs 0.000 claims description 2
- 235000019834 papain Nutrition 0.000 claims description 2
- 229940014800 succinic anhydride Drugs 0.000 claims description 2
- 239000012588 trypsin Substances 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims 3
- 239000002253 acid Substances 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- -1 carboxylic acid chlorides Chemical class 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims 1
- 230000010030 glucose lowering effect Effects 0.000 claims 1
- 230000002209 hydrophobic effect Effects 0.000 claims 1
- 239000008297 liquid dosage form Substances 0.000 claims 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims 1
- 229940119528 pork insulin Drugs 0.000 claims 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 29
- 239000008103 glucose Substances 0.000 abstract description 29
- 239000008280 blood Substances 0.000 abstract description 16
- 210000004369 blood Anatomy 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 14
- 239000000203 mixture Substances 0.000 abstract description 10
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 6
- 229940088623 biologically active substance Drugs 0.000 abstract description 3
- 210000000936 intestine Anatomy 0.000 abstract description 2
- 239000004615 ingredient Substances 0.000 abstract 2
- 208000002249 Diabetes Complications Diseases 0.000 abstract 1
- 239000013543 active substance Substances 0.000 abstract 1
- 230000000712 assembly Effects 0.000 abstract 1
- 238000000429 assembly Methods 0.000 abstract 1
- 239000004026 insulin derivative Substances 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 23
- 208000007241 Experimental Diabetes Mellitus Diseases 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000012530 fluid Substances 0.000 description 4
- 238000010171 animal model Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 230000002218 hypoglycaemic effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- IZZIWIAOVZOBLF-UHFFFAOYSA-N 5-methoxysalicylic acid Chemical compound COC1=CC=C(O)C(C(O)=O)=C1 IZZIWIAOVZOBLF-UHFFFAOYSA-N 0.000 description 2
- 208000008960 Diabetic foot Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000001904 diabetogenic effect Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000002088 nanocapsule Substances 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 229940125395 oral insulin Drugs 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- AAUQLHHARJUJEH-UHFFFAOYSA-N 2-hydroxy-5-methoxybenzoic acid Natural products COC1=CC=CC(O)=C1C(O)=O AAUQLHHARJUJEH-UHFFFAOYSA-N 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000052651 Pancreatic hormone Human genes 0.000 description 1
- 101800001268 Pancreatic hormone Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 150000004075 acetic anhydrides Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- AWKDEEXFAVIGAF-UHFFFAOYSA-N bis(4-ethenylphenyl)diazene Chemical compound C1=CC(C=C)=CC=C1N=NC1=CC=C(C=C)C=C1 AWKDEEXFAVIGAF-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 201000008980 hyperinsulinism Diseases 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000004025 pancreas hormone Substances 0.000 description 1
- 229940032957 pancreatic hormone Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229920000771 poly (alkylcyanoacrylate) Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
Landscapes
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Endocrinology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/RU2011/001061 WO2013100793A1 (ru) | 2011-12-28 | 2011-12-28 | Производное инсулина, обладающее сахароснижающей активностью, и способ его получения |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201300207A1 EA201300207A1 (ru) | 2014-01-30 |
| EA023447B1 true EA023447B1 (ru) | 2016-06-30 |
Family
ID=48698085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201300207A EA023447B1 (ru) | 2011-12-28 | 2011-12-28 | Производное инсулина, обладающее сахароснижающей активностью при пероральном применении, способ его получения и лекарственные формы на его основе |
Country Status (3)
| Country | Link |
|---|---|
| EA (1) | EA023447B1 (cs) |
| IN (1) | IN2014MN01484A (cs) |
| WO (1) | WO2013100793A1 (cs) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019098869A1 (ru) * | 2017-11-15 | 2019-05-23 | Борис Славинович ФАРБЕР | Фармацевтическая композиция для стимуляции деления стволовых клеток и подавления вирулентности бактерий |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1226104B1 (en) * | 1999-11-05 | 2009-04-08 | Emisphere Technologies, Inc. | Phenoxy carboxylic acid compounds and compositions for delivering active agents |
| US20110293714A1 (en) * | 2008-11-28 | 2011-12-01 | Novo Nordisk A/S | Pharmaceutical compositions suitable for oral administration of derivatized insulin peptides |
-
2011
- 2011-12-28 IN IN1484MUN2014 patent/IN2014MN01484A/en unknown
- 2011-12-28 WO PCT/RU2011/001061 patent/WO2013100793A1/ru active Application Filing
- 2011-12-28 EA EA201300207A patent/EA023447B1/ru not_active IP Right Cessation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1226104B1 (en) * | 1999-11-05 | 2009-04-08 | Emisphere Technologies, Inc. | Phenoxy carboxylic acid compounds and compositions for delivering active agents |
| US20110293714A1 (en) * | 2008-11-28 | 2011-12-01 | Novo Nordisk A/S | Pharmaceutical compositions suitable for oral administration of derivatized insulin peptides |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019098869A1 (ru) * | 2017-11-15 | 2019-05-23 | Борис Славинович ФАРБЕР | Фармацевтическая композиция для стимуляции деления стволовых клеток и подавления вирулентности бактерий |
| US11191767B2 (en) | 2017-11-15 | 2021-12-07 | Boris Slavinovich FARBER | Pharmaceutical composition for stimulating stem cell division and suppressing bacterial virulence |
Also Published As
| Publication number | Publication date |
|---|---|
| IN2014MN01484A (cs) | 2015-05-01 |
| WO2013100793A1 (ru) | 2013-07-04 |
| EA201300207A1 (ru) | 2014-01-30 |
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