CN1166368C - 海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用 - Google Patents
海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用 Download PDFInfo
- Publication number
- CN1166368C CN1166368C CNB031052878A CN03105287A CN1166368C CN 1166368 C CN1166368 C CN 1166368C CN B031052878 A CNB031052878 A CN B031052878A CN 03105287 A CN03105287 A CN 03105287A CN 1166368 C CN1166368 C CN 1166368C
- Authority
- CN
- China
- Prior art keywords
- injection
- omega3
- seal
- emulsion
- grams per
- 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.)
- Expired - Fee Related
Links
- 238000010253 intravenous injection Methods 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims description 6
- 239000006071 cream Substances 0.000 title 1
- 238000002347 injection Methods 0.000 claims abstract description 54
- 239000007924 injection Substances 0.000 claims abstract description 54
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 16
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 14
- 229940067606 lecithin Drugs 0.000 claims abstract description 14
- 239000000787 lecithin Substances 0.000 claims abstract description 14
- 235000010445 lecithin Nutrition 0.000 claims abstract description 14
- 239000008215 water for injection Substances 0.000 claims abstract description 14
- 239000006185 dispersion Substances 0.000 claims abstract description 11
- 238000001914 filtration Methods 0.000 claims abstract description 11
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims abstract description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
- 239000002960 lipid emulsion Substances 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 239000000839 emulsion Substances 0.000 claims description 25
- 239000007788 liquid Substances 0.000 claims description 18
- 238000007670 refining Methods 0.000 claims description 14
- 238000001816 cooling Methods 0.000 claims description 10
- 230000003292 diminished effect Effects 0.000 claims description 10
- 150000003904 phospholipids Chemical class 0.000 claims description 10
- 230000001954 sterilising effect Effects 0.000 claims description 10
- 210000000481 breast Anatomy 0.000 claims description 6
- 238000003860 storage Methods 0.000 claims description 6
- 230000004927 fusion Effects 0.000 claims description 5
- 239000011521 glass Substances 0.000 claims description 5
- 238000005360 mashing Methods 0.000 claims description 5
- 239000004576 sand Substances 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 2
- 235000013336 milk Nutrition 0.000 abstract description 9
- 239000008267 milk Substances 0.000 abstract description 9
- 210000004080 milk Anatomy 0.000 abstract description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 8
- 235000012000 cholesterol Nutrition 0.000 abstract description 4
- 239000008280 blood Substances 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 abstract description 3
- 235000004626 essential fatty acids Nutrition 0.000 abstract description 2
- 230000009467 reduction Effects 0.000 abstract description 2
- 238000000265 homogenisation Methods 0.000 abstract 1
- 230000001900 immune effect Effects 0.000 abstract 1
- 238000006722 reduction reaction Methods 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 239000013589 supplement Substances 0.000 abstract 1
- 238000001356 surgical procedure Methods 0.000 abstract 1
- 241000283216 Phocidae Species 0.000 description 22
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- 239000003925 fat Substances 0.000 description 11
- 235000019197 fats Nutrition 0.000 description 11
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- DVSZKTAMJJTWFG-UHFFFAOYSA-N docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCCC=CC=CC=CC=CC=CC=CC(O)=O DVSZKTAMJJTWFG-UHFFFAOYSA-N 0.000 description 3
- MBMBGCFOFBJSGT-KUBAVDMBSA-N docosahexaenoic acid Natural products CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 3
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 3
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 3
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 2
- YUFFSWGQGVEMMI-UHFFFAOYSA-N (7Z,10Z,13Z,16Z,19Z)-7,10,13,16,19-docosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCCCC(O)=O YUFFSWGQGVEMMI-UHFFFAOYSA-N 0.000 description 2
- YUFFSWGQGVEMMI-JLNKQSITSA-N (7Z,10Z,13Z,16Z,19Z)-docosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCCC(O)=O YUFFSWGQGVEMMI-JLNKQSITSA-N 0.000 description 2
- PIFPCDRPHCQLSJ-WYIJOVFWSA-N 4,8,12,15,19-Docosapentaenoic acid Chemical compound CC\C=C\CC\C=C\C\C=C\CC\C=C\CC\C=C\CCC(O)=O PIFPCDRPHCQLSJ-WYIJOVFWSA-N 0.000 description 2
- 235000019485 Safflower oil Nutrition 0.000 description 2
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 210000001268 chyle Anatomy 0.000 description 2
- XIVFQYWMMJWUCD-UHFFFAOYSA-N dihydrophaseic acid Natural products C1C(O)CC2(C)OCC1(C)C2(O)C=CC(C)=CC(O)=O XIVFQYWMMJWUCD-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002333 glycines Chemical class 0.000 description 2
- 210000003701 histiocyte Anatomy 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000003170 nutritional factors Nutrition 0.000 description 2
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 2
- 229940033080 omega-6 fatty acid Drugs 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 235000005713 safflower oil Nutrition 0.000 description 2
- 239000003813 safflower oil Substances 0.000 description 2
- 229940031439 squalene Drugs 0.000 description 2
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010004103 Chylomicrons Proteins 0.000 description 1
- PIFPCDRPHCQLSJ-UHFFFAOYSA-N Clupanodonic acid Natural products CCC=CCCC=CCC=CCCC=CCCC=CCCC(O)=O PIFPCDRPHCQLSJ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 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 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 206010018873 Haemoconcentration Diseases 0.000 description 1
- 206010060766 Heteroplasia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000269799 Perca fluviatilis Species 0.000 description 1
- 241001529469 Phoca groenlandica Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000680 avirulence Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 1
- 230000003544 deproteinization Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 230000002366 lipolytic effect Effects 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 235000021290 n-3 DPA Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000010461 other edible oil Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011046 pyrogen test Methods 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000002620 vena cava superior Anatomy 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
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
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/35—Fat tissue; Adipocytes; Stromal cells; Connective tissues
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Virology (AREA)
- Developmental Biology & Embryology (AREA)
- Biotechnology (AREA)
- Dispersion Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Nutrition Science (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及OMEGA3海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用，该OMEGA3海狗油脂肪乳注射液的主要成分及配比为精制OMEGA3海狗油190-210克/升、精制卵磷脂11-13克/升、注射用甘油24-26克/升、其余为注射用水，该OMEGA3海狗油脂肪乳注射液的制备方法包括搅拌分散、高压匀化、减压过滤及消毒和装瓶步骤，本发明OMEGA3海狗油脂肪乳注射液其能量密度高，极易被人体吸收，既能供给人体热能，又能补充人体必需的脂肪酸，具有提高机体免疫能力，降低胆固醇，调整血液浓度以及抗炎作用，特别对术后病人迅速恢复体力有很大帮助。
Description
技术领域
本发明涉及海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用。更确切地说，本发明涉及OMEGA3海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用。
背景技术
脂肪是热能值最高的营养要素，每克脂肪供热量为9.3千克。人体的能源绝大部分是以脂肪形式储存的，当人体遭遇创伤和各种疾病而能量供给不足时，就会利用自身储存的脂肪产生热能，同时将机体蛋白(主要是肌肉蛋白)经糖元异生合成所需的葡萄糖，以维持机体的代谢功能。
人体正常摄取食物脂肪后，在肠内经胆盐先乳化成小于0.5μm的细微胶粒，进而被脂解酶分解为脂肪酸和甘油酯，经扩散作用由肠壁黏膜吸收，在肠黏膜细胞内再合成甘油三酯，与一部分蛋白和α-磷酸甘油酯结合构成乳糜，进入肠壁淋巴管，汇集到胸管后进入上腔静脉。当创伤和疾病导致人体不能经口服进食而失去摄取脂肪的功能时，需经静脉注射此类营养要素，这样就须将脂肪类物质配制成小于1μm的乳糜微粒，从体外注入静脉，供组织细胞利用。脂肪乳就是这种人造的乳糜液，它对满足人体能量需要、保持细胞膜生态以及提高免疫能力具有重要作用。
现有技术中生产的脂肪乳大多以豆油、红花油为主要成分，例如，CN1376460A公开了一种注射用脂肪乳剂及其制造方法，该脂肪乳剂的成分为纯化大豆油270-330克/升，精制卵磷脂11-13克/升，无水甘油15-18克/升，氢氧化钠适量，其余为注射用水。国内外尚未见采用OMEGA3海狗油制备脂肪乳注射液的报道。
本发明的脂肪乳注射液以精制OMEGA3海狗油为主要成分。海狗为海豹科动物竖琴海豹(harp seal)的俗称，栖居于北极和大西洋的北部。由于加拿大政府采取的保护措施，海狗的数量以每年7％的速度稳定增长。为保持海狗与鱼群之间的生态平衡，经加拿大政府批准，每年可以少量地捕杀海狗。本发明产品取材于新捕猎的北极海狗皮下脂肪，经过真空蒸馏等工艺，在低温条件下除去蛋白、碳水化合物等物质，得到呈微黄色、透明液体状的精炼OMEGA3海狗油。OMEGA3海狗油中富含人体必需的体内不能自行合成的Ω-3型多碳不饱和脂肪酸，其营养价值优于其它食用油类。在OMEGA3海狗油中除发现鱼油中通常含有的二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)外，还有含量可观的二十二碳五烯酸(DPA)。理想条件下提炼加工的OMEGA3海狗油，其中EPA、DHA和DPA的含量可达25％左右。OMEGA3海狗油中还含有少量的角鲨烯(SQUALENE)，且几乎不含胆固醇。OMEGA3海狗油含有大量的Ω-3型脂肪酸，而豆油、红花油主要含有Ω-6脂肪酸。由于OMEGA3海狗油其分子结构与人体内的脂肪酸分子结构相似，用OMEGA3海狗油制备的脂肪乳注射液极易被人体吸收利用，特别是近二十年来医学界不断研究Ω-3和Ω-6的平衡对身体健康十分重要，联合国卫生组织要求人类Ω-3和Ω-6的比例应为1∶1，由于目前饮食的关系人身体脂肪的比例为1∶35，Ω-3脂肪酸少，Ω-6脂肪酸太多，两者比例极不平衡，所以用OMEGA3海狗油制备的脂肪乳注射液其效用优于普通脂肪乳注射液。
本发明OMEGA3海狗油脂肪乳注射液既能供给人体热能，又能补充人体必需的脂肪酸，具有提高机体免疫能力，降低胆固醇，调整血液浓度以及抗炎作用，特别对术后病人迅速恢复体力有很大帮助。
发明内容
本发明目的是提供一种OMEGA3海狗油脂肪乳注射液，其主要成分为精制OMEGA3海狗油，它是既能供给人体热能，又能补充必需脂肪酸的营养乳液。
本发明另一个目的是提供该OMEGA3海狗油脂肪乳注射液的制备方法，该方法工艺独特，操作简便。
本发明还有一个目的是提供该OMEGA3海狗油脂肪乳注射液在制备静脉注射剂中的应用。
本发明的一种OMEGA3海狗油脂肪乳注射液，其特征在于主要成分及配比如下：
精制OMEGA3海狗油 190-210克/升
精制卵磷脂 11-13克/升
注射用甘油 24-26克/升
注射用水 加至1000毫升
本发明的一种OMEGA3海狗油脂肪乳注射液，其特征在于主要成分及配比优选如下：
精制OMEGA3海狗油 200克/升
精制卵磷脂 12克/升
注射用甘油 25克/升
注射用水 加至1000毫升
该产品性状为白色乳状液体(即水包油型)，用电泳法测定乳剂球粒带负电荷，球粒均匀分散，直径在1μm以下。
本发明的一种OMEGA3海狗油脂肪乳注射液的制备方法，其特征在于该方法包括如下步骤：
(1)搅拌分散，按规定配比称取各成分，将精制卵磷脂置于高速组织捣碎机内，加注射用甘油及适量的注射用水，在氮气流下搅拌成均匀的磷脂分散液，将其倾入二步匀化机中的储液瓶内，不断通入氮气；
(2)高压匀化，在低压为105kg/cm2，高压为317kg/cm2的加压状态下，使精制OMEGA3海狗油和磷脂分散液进行匀化以形成粗乳，然后使该乳化液在氮气流下，在两个储瓶之间环流匀化，至三次循环时加注射用水，经循环七次后，至油粒直径达到1μm以下时，小心调节该乳液的PH至5.5-7.0，放出乳液；
(3)减压过滤，使收集到的乳液冷却，在氮气流下用4号垂熔玻砂漏斗减压过滤至无异物；
(4)消毒和装瓶，在氮气流下装瓶、扎盖，经90℃预热，再经120℃灭菌15分钟，冲热水降温，放置室温即得产品。
本发明产品经用常规方法进行粒径测定、溶血试验、热原检查、油及甘油含量测定、过氧化值、酸价、PH值等项检查合格后进行包装，包装规格为100毫升/瓶×10瓶/箱，25℃以下储存，使用前摇匀。本发明产品最好常年放置冰箱内冷藏为宜，非低温储存会使油粒凝聚变大，此外储存时严禁冰冻，否则乳液会破坏。
本发明还提供了该OMEGA3海狗油脂肪乳注射液在制备静脉注射剂中的应用，本发明产品为手术后、短期内供机体利用的一种高热能输液，并能补充人体必需的脂肪酸，如与足够的蛋白质和碳水化合物配合应用，对手术后早期因分解代谢所引起的负氮平衡，有显著降低效果。
本发明OMEGA3海狗油脂肪乳注射液用于静脉滴注时其用量对成人而言，每天平均输注脂肪量每公斤体重不超过2.5g。每次输注时速率最初15-30分钟内，每分钟应控制在1ml，如无并发症，速率可增加到每小时80-100ml。
本发明OMEGA3海狗油脂肪乳注射液的急性毒性试验如下：
选用体重为12公斤左右的狗8条，在动物正常清醒状态下，以6g脂肪/公斤体重的剂量，一次静脉滴注给药，一周后病理切片检查各组织细胞均无明显异常，结果表明本发明产品无毒性。
临床试验35例成年人经静脉输注本发明OMEGA3海狗油脂肪乳注射液后，血甘油三酯水平，血总胆固醇浓度基本无变化并略有下降，结果表明，应用本发明OMEGA3海狗油脂肪乳注射液不会产生高脂血症等副作用。
具体实施方式：
下列实施例仅为了进一步说明本发明，而不是限制本发明。
实施例1
取精制OMEGA3海狗油200克/升、精制卵磷脂12克/升、注射用甘油25克/升、其余为注射用水的配比，按下列步骤制备OMEGA3海狗油脂肪乳注射液：
(1)搅拌分散，将精制卵磷脂置于高速组织捣碎机内，加注射用甘油及适量的注射用水，在氮气流下搅拌成均匀的磷脂分散液，将其倾入二步匀化机中的储液瓶内，不断通入氮气；
(2)高压匀化，在低压为105kg/cm2，高压为317kg/cm2的加压状态下，使精制OMEGA3海狗油和磷脂分散液进行匀化以形成粗乳，然后使该乳化液在氮气流下，在两个储瓶之间环流匀化，至三次循环时加注射用水，经循环七次后，至油粒直径达到1μm以下时，调节该乳液PH至6.3，放出乳液；
(3)减压过滤，使收集到的乳液冷却，在氮气流下用4号垂熔玻砂漏斗减压过滤至无异物；
(4)消毒和装瓶，在氮气流下装瓶、扎盖，经90℃预热，再经120℃灭菌15分钟，冲热水降温，放置室温即得产品。
实施例2
取精制OMEGA3海狗油190克/升、精制卵磷脂11克/升、注射用甘油24克/升、其余为注射用水的配比，按下列步骤制备OMEGA3海狗油脂肪乳注射液：
(1)搅拌分散，将精制卵磷脂置于高速组织捣碎机内，加注射用甘油及适量的注射用水，在氮气流下搅拌成均匀的磷脂分散液，将其倾入二步匀化机中的储液瓶内，不断通入氮气；
(2)高压匀化，在低压为105kg/cm2，高压为317kg/cm2的加压状态下，使精制OMEGA3海狗油和磷脂分散液进行匀化以形成粗乳，然后使该乳化液在氮气流下，在两个储瓶之间环流匀化，至三次循环时加注射用水，经循环七次后，至油粒直径达到1μm以下时，调节该乳液PH至5.5，放出乳液；
(3)减压过滤，使收集到的乳液冷却，在氮气流下用4号垂熔玻砂漏斗减压过滤至无异物；
(4)消毒和装瓶，在氮气流下装瓶、扎盖，经90℃预热，再经120℃灭菌15分钟，冲热水降温，放置室温即得产品。
实施例3
取精制OMEGA3海狗油210克/升、精制卵磷脂13克/升、注射用甘油26克/升、其余为注射用水的配比，按下列步骤制备OMEGA3海狗油脂肪乳注射液：
(1)搅拌分散，将精制卵磷脂置于高速组织捣碎机内，加注射用甘油及适量的注射用水，在氮气流下搅拌成均匀的磷脂分散液，将其倾入二步匀化机中的储液瓶内，不断通入氮气；
(2)高压匀化，在低压为105kg/cm2，高压为317kg/cm2的加压状态下，使精制OMEGA3海狗油和磷脂分散液进行匀化以形成粗乳，然后使该乳化液在氮气流下，在两个储瓶之间环流匀化，至三次循环时加注射用水，经循环七次后，至油粒直径达到1μm以下时，调节该乳液PH至7.0，放出乳液；
(3)减压过滤，使收集到的乳液冷却，在氮气流下用4号垂熔玻砂漏斗减压过滤至无异物；
(4)消毒和装瓶，在氮气流下装瓶、扎盖，经90℃预热，再经120℃灭菌15分钟，冲热水降温，放置室温即得产品。
Claims (4)
1.OMEGA3海狗油脂肪乳注射液，其特征在于主要成分及配比如下：
精制OMEGA3海狗油 190-210克/升
精制卵磷脂 11-13克/升
注射用甘油 24-26克/升
其余为注射用水。
2.权利要求1所述的OMEGA3海狗油脂肪乳注射液，其特征在于主要成分及配比如下：
精制OMEGA3海狗油 200克/升
精制卵磷脂 12克/升
注射用甘油 25克/升
其余为注射用水。
3.权利要求1所述的OMEGA3海狗油脂肪乳注射液的制备方法，其特征在于该方法包括如下步骤：
(1)搅拌分散，按规定配比称取各成分，将精制卵磷脂置于高速组织捣碎机内，加注射用甘油及适量的注射用水，在氮气流下搅拌成均匀的磷脂分散液，将其倾入二步匀化机中的储液瓶内，不断通入氮气；
(2)高压匀化，在低压为105kg/cm2，高压为317kg/cm2的加压状态下，使精制OMEGA3海狗油和磷脂分散液进行匀化以形成粗乳，然后使该乳化液在氮气流下，在两个储瓶之间环流匀化，至三次循环时加注射用水，经循环七次后，至油粒直径达到1μm以下时，小心调节该乳液的PH至5.5-7.0，放出乳液；
(3)减压过滤，使收集到的乳液冷却，在氮气流下用4号垂熔玻砂漏斗减压过滤至无异物；
(4)消毒和装瓶，在氮气流下装瓶、扎盖，经90℃预热，再经120℃灭菌15分钟，冲热水降温，放置室温即得产品。
4.权利要求1所述的OMEGA3海狗油脂肪乳注射液在制备静脉注射剂中的应用。
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031052878A CN1166368C (zh) | 2003-02-26 | 2003-02-26 | 海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用 |
| JP2004568621A JP2006519165A (ja) | 2003-02-26 | 2003-08-11 | アザラシ油ベースの脂質エマルジョン注射物、その調製および静脈注射物の調製のためのその使用 |
| KR1020057015959A KR20050120755A (ko) | 2003-02-26 | 2003-08-11 | 해구유 유래 지질 에멀젼 주사제, 그의 제조방법 및 그의정맥내 주사제제로의 용도 |
| EP03816023A EP1616560A1 (en) | 2003-02-26 | 2003-08-11 | Fatty emulsion injection of seal oil, method for preparation and the use in manufacturing intravenous injection |
| PCT/CN2003/000658 WO2004075878A1 (fr) | 2003-02-26 | 2003-08-11 | Composition a injecter d'huile de phoque sous forme d'emulsion grasse, son procede de preparation et son utilisation dans la production d'un produit pour injection intraveineuse |
| AU2003252527A AU2003252527A1 (en) | 2003-02-26 | 2003-08-11 | Fatty emulsion injection of seal oil, method for preparation and the use in manufacturing intravenous injection |
| US10/547,027 US20060292226A1 (en) | 2003-02-26 | 2003-08-11 | Fatty emulsion injection of seal oil, method for preparation and the use in manufacturing intravenous injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031052878A CN1166368C (zh) | 2003-02-26 | 2003-02-26 | 海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1432367A CN1432367A (zh) | 2003-07-30 |
| CN1166368C true CN1166368C (zh) | 2004-09-15 |
Family
ID=27634068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031052878A Expired - Fee Related CN1166368C (zh) | 2003-02-26 | 2003-02-26 | 海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20060292226A1 (zh) |
| EP (1) | EP1616560A1 (zh) |
| JP (1) | JP2006519165A (zh) |
| KR (1) | KR20050120755A (zh) |
| CN (1) | CN1166368C (zh) |
| AU (1) | AU2003252527A1 (zh) |
| WO (1) | WO2004075878A1 (zh) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1331467C (zh) * | 2004-10-09 | 2007-08-15 | 中国药品生物制品检定所 | 一种海狗油注射乳剂及其制备方法 |
| WO2007058523A1 (en) * | 2005-11-17 | 2007-05-24 | N.V. Nutricia | Composition with docosapentaenoic acid |
| CN100386029C (zh) * | 2005-12-30 | 2008-05-07 | 山东师范大学 | 脱除海狗油腥臭味的方法 |
| JP5951489B2 (ja) * | 2009-10-16 | 2016-07-13 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーＧｌａｘｏＳｍｉｔｈＫｌｉｎｅ ＬＬＣ | 組成物 |
| DE102009056883B4 (de) * | 2009-12-03 | 2012-08-16 | Novartis Ag | Impfstoff-Adjuvantien und verbesserte Verfahren zur Herstellung derselben |
| DE102009056871A1 (de) * | 2009-12-03 | 2011-06-22 | Novartis AG, 4056 | Impfstoff-Adjuvantien und verbesserte Verfahren zur Herstellung derselben |
| CN101797270B (zh) * | 2009-12-23 | 2012-08-01 | 王京南 | 蚕蛹油脂肪乳静脉注射液及制造方法 |
| CN101822839B (zh) * | 2010-03-31 | 2012-01-04 | 首都医科大学 | 以海豹油为液相基质的纳米结构脂质载体的制备及应用 |
| CN101991535A (zh) * | 2010-11-16 | 2011-03-30 | 王京南 | Dha酯脂肪乳静脉注射液及其制造方法 |
| CN101991534A (zh) * | 2010-11-16 | 2011-03-30 | 王京南 | Epa酯脂肪乳静脉注射液及制造方法 |
| CN102512367B (zh) * | 2011-12-26 | 2014-02-12 | 西安力邦制药有限公司 | 二十二碳六烯酸(dha)脂肪乳制剂配方和制备方法 |
| CN111150706A (zh) * | 2020-02-28 | 2020-05-15 | 深圳市金枫生物医药科技有限公司 | 一种含有元宝枫籽油的亚微乳及其制备方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4678808A (en) * | 1985-10-15 | 1987-07-07 | Baxter Travenol Laboratories, Inc. | Rapid acting intravenous emulsions of omega-3 fatty acid esters |
| WO1993021912A1 (de) * | 1992-04-28 | 1993-11-11 | Fresenius Ag | Verwendung einer omega-3-fettsäuren enthaltenden emulsion zur herstellung eines parenteral zu verabreichenden arzneimittels zur behandlung von entzündlichen erkrankungen |
| JPH0930962A (ja) * | 1995-07-21 | 1997-02-04 | Nisshin Oil Mills Ltd:The | 医療用油脂含有組成物 |
| JP3615284B2 (ja) * | 1995-08-31 | 2005-02-02 | 味の素ファルマ株式会社 | 脂肪乳剤の製造法 |
| JP3695499B2 (ja) * | 1997-03-12 | 2005-09-14 | ニプロ株式会社 | 脂肪乳剤 |
| CA2290885A1 (fr) * | 1999-12-02 | 2001-06-02 | Universite De Sherbrooke | Methode pour la transformation des tissus du loup marin |
| GB0012597D0 (en) * | 2000-05-25 | 2000-07-12 | Astrazeneca Ab | Formulation |
| PT102509A (pt) * | 2000-08-16 | 2002-02-28 | Fundacao Essprit Icarus | Composicoes farmaceuticas, cosmeticas e dermo-cosmeticas, de higiene, alimentares e para-alimentares a base de oleo de foca, e sua utilizacao |
| US7799365B2 (en) * | 2001-04-06 | 2010-09-21 | Burnbrae Farms Limited | Liquid egg composition including fish oil with omega-3 fatty acid |
-
2003
- 2003-02-26 CN CNB031052878A patent/CN1166368C/zh not_active Expired - Fee Related
- 2003-08-11 US US10/547,027 patent/US20060292226A1/en not_active Abandoned
- 2003-08-11 EP EP03816023A patent/EP1616560A1/en not_active Withdrawn
- 2003-08-11 KR KR1020057015959A patent/KR20050120755A/ko not_active Application Discontinuation
- 2003-08-11 WO PCT/CN2003/000658 patent/WO2004075878A1/zh active Application Filing
- 2003-08-11 JP JP2004568621A patent/JP2006519165A/ja active Pending
- 2003-08-11 AU AU2003252527A patent/AU2003252527A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2006519165A (ja) | 2006-08-24 |
| US20060292226A1 (en) | 2006-12-28 |
| AU2003252527A1 (en) | 2004-09-17 |
| CN1432367A (zh) | 2003-07-30 |
| WO2004075878A1 (fr) | 2004-09-10 |
| KR20050120755A (ko) | 2005-12-23 |
| EP1616560A1 (en) | 2006-01-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1166368C (zh) | 海狗油脂肪乳注射液、其制备方法及其在制备静脉注射剂中的应用 | |
| JPH07507327A (ja) | 神経系損傷を有するヒトのための栄養製剤 | |
| CN1553798A (zh) | 修改器官和组织细胞膜的脂肪酸组合物 | |
| CN103687495A (zh) | 包含维生素k2的组合物 | |
| EP0687418A2 (en) | A lipid composition, its use for normalizing injury response | |
| CN102215839B (zh) | 用于人工喂养重病的重症特护患者的脂肪乳剂 | |
| CN109393493A (zh) | 一种含hmb钙的预消化型全营养液及其制备方法 | |
| CA1249523A (en) | Method for directed visceral metabolism of medium chain triglycerides | |
| KR102195090B1 (ko) | 오메가 지방산을 포함하는 약학 조성물 및 이를 포함하는 수액제제 | |
| JPH07508720A (ja) | 異化代謝の病気の影響を最小限にするための食餌療法用補給物としてのモノ不飽和脂肪 | |
| CN1348983A (zh) | 从植物果仁中提取的果仁油组合物、提取方法及其应用 | |
| EP0696453A2 (en) | Pediatric lipid emulsion | |
| US7101584B2 (en) | Micro-molecular hyper-saturation of conventional cooking oils for high altitude and confined space applications | |
| CN105770902A (zh) | 一种ω-3鱼油中长链脂肪乳注射液药物组合物及其制备方法 | |
| CN112352837A (zh) | 一种含不饱和脂肪酸的调制乳及其制备方法 | |
| AU634537B2 (en) | Pharmaceutical lipid composition for parenteral nutrition | |
| JP4167849B2 (ja) | 植物の果実から抽出した果実油、その抽出方法、医薬組成物およびその用途 | |
| JP2007262088A (ja) | 栄養輸液製剤 | |
| CN104189058B (zh) | 一种含左卡尼汀的脂肪乳注射液 | |
| CN101015566A (zh) | 用骆驼乳和马来酸罗格列酮联合治疗ⅱ型糖尿病 | |
| CN101695487B (zh) | 一种高纯度epa-e、dha-e的多烯酸乙酯乳剂 | |
| CN1943590A (zh) | 一种治疗干眼症的人工泪液 | |
| CN1778373A (zh) | 保健组合物 | |
| CN101190248A (zh) | 一种荠蓝油中长链脂肪乳口服或注射制剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Liu Junxiang Document name: Notification to Pay the Fees |
|
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Liu Junxiang Document name: Notification to Pay the Fees |
|
| DD01 | Delivery of document by public notice |
Addressee: Liu Wei Document name: Notification to Pay the Fees |
|
| DD01 | Delivery of document by public notice |
Addressee: Liu Wei Document name: Notification of Termination of Patent Right |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20151217 Address after: 250002, Shandong, Ji'nan Province Shun Shun Road No. 28, Shun Geng Village, Hong Shun court 4 Patentee after: Shandong sun tree Bioengineering Co., Ltd. Address before: 100026, room four, unit 8, South Building, middle Tuanjiehu Road, Beijing, Chaoyang District, Patentee before: Liu Wei Patentee before: Liu Junxiang Patentee before: He Weijian Patentee before: Liu Yun |
|
| DD01 | Delivery of document by public notice |
Addressee: Liu Junxiang Document name: Notification of Passing Examination on Formalities |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160622 Address after: Ping Pingyin County of Ji'nan City, Shandong province 250400 Street No. 15 Patentee after: Shandong Inuit biological Polytron Technologies Inc Address before: 250002, Shandong, Ji'nan Province Shun Shun Road No. 28, Shun Geng Village, Hong Shun court 4 Patentee before: Shandong sun tree Bioengineering Co., Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20040915 Termination date: 20200226 |