EP0837882A1 - Kollagen peptid fraktion und deren verwendung - Google Patents
Kollagen peptid fraktion und deren verwendungInfo
- Publication number
- EP0837882A1 EP0837882A1 EP96920798A EP96920798A EP0837882A1 EP 0837882 A1 EP0837882 A1 EP 0837882A1 EP 96920798 A EP96920798 A EP 96920798A EP 96920798 A EP96920798 A EP 96920798A EP 0837882 A1 EP0837882 A1 EP 0837882A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- cpf
- collagen
- collagen peptide
- peptide fraction
- fraction
- 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.)
- Withdrawn
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 49
- 102000008186 Collagen Human genes 0.000 title claims abstract description 42
- 108010035532 Collagen Proteins 0.000 title claims abstract description 42
- 229920001436 collagen Polymers 0.000 title claims abstract description 42
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 31
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 31
- 229940079593 drug Drugs 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 17
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 15
- 230000000699 topical effect Effects 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000001802 infusion Methods 0.000 claims abstract description 5
- 230000007774 longterm Effects 0.000 claims abstract description 5
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims abstract description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000004471 Glycine Substances 0.000 claims abstract description 3
- 238000002835 absorbance Methods 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 13
- 238000010438 heat treatment Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000006641 stabilisation Effects 0.000 claims description 8
- 102000004190 Enzymes Human genes 0.000 claims description 7
- 108090000790 Enzymes Proteins 0.000 claims description 7
- 238000001179 sorption measurement Methods 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000000427 antigen Substances 0.000 claims description 4
- 102000036639 antigens Human genes 0.000 claims description 4
- 108091007433 antigens Proteins 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 238000002965 ELISA Methods 0.000 claims description 3
- 230000001900 immune effect Effects 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 238000012545 processing Methods 0.000 claims description 3
- 238000001042 affinity chromatography Methods 0.000 claims description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- 235000014571 nuts Nutrition 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 abstract description 7
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 abstract description 3
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 abstract description 3
- 229960002591 hydroxyproline Drugs 0.000 abstract description 3
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 abstract description 3
- 230000003019 stabilising effect Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 22
- 108091006905 Human Serum Albumin Proteins 0.000 description 13
- 102000008100 Human Serum Albumin Human genes 0.000 description 13
- 229940088598 enzyme Drugs 0.000 description 6
- 102000012422 Collagen Type I Human genes 0.000 description 5
- 108010022452 Collagen Type I Proteins 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 102000009027 Albumins Human genes 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 108090000190 Thrombin Proteins 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102000057297 Pepsin A Human genes 0.000 description 3
- 108090000284 Pepsin A Proteins 0.000 description 3
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 3
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 229940111202 pepsin Drugs 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 229960000187 tissue plasminogen activator Drugs 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- OIPPWFOQEKKFEE-UHFFFAOYSA-N orcinol Chemical compound CC1=CC(O)=CC(O)=C1 OIPPWFOQEKKFEE-UHFFFAOYSA-N 0.000 description 2
- 229940092253 ovalbumin Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 230000036515 potency Effects 0.000 description 2
- 239000003805 procoagulant Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical compound [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102000017975 Protein C Human genes 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000012505 colouration Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- -1 phosphate anions Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 229960004319 trichloroacetic acid Drugs 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
Definitions
- the present invention relates to a new collagen peptide fraction (CPF) consisting of several peptide species which can among others be used for the stabilisation of protein and peptide drugs during long term infusion, of liquid forms of protein and peptide drugs and of freeze dried respectively lyophilised proteins and peptides or freeze dried respectively lyophilised drugs containing proteins and peptides for topical, nasal or transdermal application.
- CPF collagen peptide fraction
- Bioly active proteins in their natural environment are stabilized within a balanced system of biopolymers, carbohydrates and electrolytes. Maintenance of stability during handling and storage of highly purified proteins and polypeptides for therapeutic and other uses requires special procedures.
- Lyophilized pharmaceutical preparations in general may contain bulking agents (eg amino acids, carbohydrates or polyalcohols) , inorganic or organic buffer substances, electrolytes and bacteriostatics. Every single component of a freeze dried preparation has to be compatible with each other and the total composition has to provide an optimum environment for the stability of the active ingredient in the freeze dried state.
- bulking agents eg amino acids, carbohydrates or polyalcohols
- inorganic or organic buffer substances e.g electrolytes and bacteriostatics.
- a composition that provides stability in a freeze dried state is not necessarily best for drug stability in solution after reconstitution. This is of minor importance if the preparation is injected immediately after reconstitution. It may cause major problems, however, if the reconstituted drug has to be continuously infused during a prolonged time period.
- the composition of the respective pharmaceutical preparation has to guarantee maximum stability in the freeze dried state as well as after reconstitution.
- Loss of protein activity in solution may be caused by sub- optimal pH and ionic strength, autocatalytic degradation, heat, oxygen, surface denaturation, adsorbant surfaces, shear forces, high pressure, irradiation, etc.
- HSA human serum albumin
- BSA bovine serum albumin
- ovalbumin are strong antigens and can therefore not be used for the stabilization of injectable drugs.
- Human serum albumin is not antigenic to humans but it can bear a risk of viral (HIV, hepatitis) and mycoplasma contamination.
- a further disadvantage of HSA as a stabilizing agent involves the possible contamination with other biologically active materials eg proteinases or proteinase inhibitors that may interact with the protein to be stabilized (see M.C.E. Van Dam-Mieras, A.D.
- HSA is similarly disadvantageous when used in topical applications.
- solubilized collagen cannot be used in injectable preparations because of its activating effect on platelet aggregation.
- a further disadvantage of solubilized collagen is its high viscosity in solution and its instability. Heating over 40°C causes denaturation of collagen and subsequent gel formation upon cooling to room temperature. Addition of phosphate anions to collagen causes the formation of an insoluble gel.
- collagen following partial acid hydrolysis into lower molecular peptides, could still exhibit protein stabilising properties, did not cause platelets to aggregate, formed low viscosity solutions and was compatible with current buffering substances including phosphates. This was named as a collagen peptide fraction (CPF) .
- CPF collagen peptide fraction
- CPF was capable of saturating or blocking protein adsorbing or covalently binding sites of glass and synthetic or natural polymers in preparative, analytical, diagnostic and medical devices such as microtiter plates, blotting membranes, filters, tubings etc.
- a treatment by rinsing or incubation with CPF solution can therefore be used to prevent unspecific antibody or antigen binding in immunological techniques such as enzyme linked immuno adsorption (ELISA), immunoblotting and related procedures.
- ELISA enzyme linked immuno adsorption
- Incubation with CPF can also be used to saturate excessive active groups in activated supports for affinity chro atography, and washing with CPF of filter material, glass or plastic ware will prevent adsorption of proteins from solutions during processing.
- CPF collagen peptide fraction
- CPF collagen peptide fraction
- CPF collagen peptide fraction
- CPF collagen peptide fraction
- Collagen suitable for the production of a collagen peptide fraction (CPF) according to the present invention is obtainable from animal tissues, preferably pig skin.
- Pepsin solubilized type I collagen can be prepared by conventional techniques eg according to the method of N D Light, 1985.
- Collagen in Skin Preparation and Analysis, in: Methods in Skin Research (D Skerrow and C J Skerrow, Eds) J Wiley and Sons Ltd. p 559-585.
- Controlled hydrolysis of type I collagen can be performed by heating an aqueous collagen suspension at low pH for a defined time period.
- a collagen peptide fraction (CPF) according to the invention is obtainable by heating a collagen suspension at pH 2.5-4.0 for 30-90 minutes at 100 -150°C in an autoclave.
- the parameters (pH, temperature, time) can be varied to a wide extent. E.g. low pH and high temperature will reduce the heating time.
- a collagen peptide fraction (CPF) consists of several peptide species, >70%, especially >80%, of which have an average molecular weight of 8-30 kDa, especially 8 to 25 kDa, more especially 10-20 kDa, most especially 20 kDa (estimated by gel permeation chromatography), a hydroxyproline content of 15-19%, a proline content of 18-22% and a glycine content of 27-33% (according to D.H. Spackman et al., Anal. Chem. 30, 1190-1206, (1958)).
- a mixture of equal volumes of 10% aqueous CPF solution and 10% trichloro- -acetic acid does not form any protein precipitate while albumin or gelatin, under similar conditions form strong precipitates.
- a CPF solution in 5% ammonia after heating to 95°C with 1 ml silver nitrate, 0.1 M, does not show any brownish colouration, whereas gelatin under similar conditions, due to its content of reducing carbohydrates, shows a dark brown colour.
- reducing carbohydrates originating from glucosaminoglycan degradation produce a strong orcinol colour reaction whereas CPF shows a very weak reaction only.
- Type I collagen from pig skin was purified according to Light (see ref. above). Freshly frozen pig skin was ground and defatted by solvent extraction. The resulting skin fibre pulp was treated with pepsin to solubilize type I collagen. Insoluble material was removed by filtration, collagen was precipitated from the filtrate at pH 7.5, dissolved in saline and further purified by salt fractionation and ion exchange treatments. Precipitated type I collagen was suspended in water, the pH adjusted to 3.5 with hydrochloric acid, the acidified suspension was heated in an autoclave for 60 min at 145°C, the concentration was adjusted with water to 10 ⁇ 1% solids.
- Figure 2 shows that the activity of TPA which is commonly used in therapy as an infusion also suffered less loss of activity when incubated with CPF rather than HSA at 37°C.
- the loss in the activities during lyophilisation was approximately similar for CPF and HSA and the potencies of the enzymes lyophilized from CPF solutions were similar to those lyophilized from HSA solutions following storage for 12 weeks over a wide range of temperatures. Only at a severely elevated temperature (e.g.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96920798A EP0837882A1 (de) | 1995-06-10 | 1996-06-06 | Kollagen peptid fraktion und deren verwendung |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP95108967 | 1995-06-10 | ||
| EP95108967 | 1995-06-10 | ||
| EP96920798A EP0837882A1 (de) | 1995-06-10 | 1996-06-06 | Kollagen peptid fraktion und deren verwendung |
| PCT/EP1996/002453 WO1996041817A1 (en) | 1995-06-10 | 1996-06-06 | Collagen peptide fraction and its uses |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0837882A1 true EP0837882A1 (de) | 1998-04-29 |
Family
ID=8219349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP96920798A Withdrawn EP0837882A1 (de) | 1995-06-10 | 1996-06-06 | Kollagen peptid fraktion und deren verwendung |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0837882A1 (de) |
| JP (1) | JPH11507918A (de) |
| AU (1) | AU6222896A (de) |
| WO (1) | WO1996041817A1 (de) |
| ZA (1) | ZA964825B (de) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3343712B2 (ja) * | 1995-12-27 | 2002-11-11 | 宮城化学工業株式会社 | 非抗原性安定化剤および生理活性物質 |
| US20070031501A1 (en) * | 2003-08-05 | 2007-02-08 | Andries Van Es | Use of recombinant or synthetic gelatin-like proteins as stabiliser in lyophilized pharmaceutical compositions |
| JP4045289B2 (ja) * | 2006-04-12 | 2008-02-13 | 株式会社エーシーバイオテクノロジーズ | コラーゲン類生産方法及びコラーゲン類 |
| ES2670745T3 (es) | 2007-05-17 | 2018-05-31 | Advance Dx, Inc. | Tarjeta de recolección de separador de fluidos |
| JP2010143860A (ja) * | 2008-12-19 | 2010-07-01 | Chisso Corp | タンパク質の安定化剤 |
| JP5803104B2 (ja) * | 2010-12-28 | 2015-11-04 | 東ソー株式会社 | 安定化されたｓ−アデノシルホモシステイン加水分解酵素調製物 |
| WO2014008454A2 (en) * | 2012-07-06 | 2014-01-09 | Jnc Corporation | Aspirin response and reactivity test and aspirin compliance test using synthetic collagen |
| JP6183459B2 (ja) * | 2012-08-06 | 2017-08-23 | Jnc株式会社 | 合成コラーゲンを用いる二重抗血小板薬／アスピリン応答および反応性試験 |
| US20150198620A1 (en) * | 2012-08-09 | 2015-07-16 | Jnc Corporation | Anti-platelet response and reactivity test using synthetic collagen |
| US10088397B2 (en) | 2013-06-19 | 2018-10-02 | Advance Dx, Inc. | Fluid separator collection card assembly |
| JP2014088409A (ja) * | 2013-12-20 | 2014-05-15 | Jnc Corp | タンパク質の安定化剤 |
| JP2016011310A (ja) * | 2015-10-14 | 2016-01-21 | Jnc株式会社 | タンパク質の安定化剤 |
| US10610862B2 (en) | 2016-04-04 | 2020-04-07 | Advance Dx, Inc. | Multiple path sample collection card |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1227534A (de) * | 1967-08-31 | 1971-04-07 | ||
| US3608083A (en) * | 1968-06-05 | 1971-09-21 | Hoffmann La Roche | Vitamin e powder |
| US4285986A (en) * | 1980-01-21 | 1981-08-25 | Seton Company | Oligopeptides derived from collagen |
| US4307013A (en) * | 1980-10-02 | 1981-12-22 | Nippi, Incorporated | Method for removing antigenicity from peptide |
| JPS5785051A (en) * | 1980-11-18 | 1982-05-27 | Toppan Printing Co Ltd | Water-soluble photosensitive material |
| JPS58111661A (ja) * | 1981-12-24 | 1983-07-02 | Nippon Kayaku Co Ltd | 畜肉・魚肉加工品の製造法 |
| JPS59196824A (ja) * | 1983-04-21 | 1984-11-08 | Kowa Co | 吸着防止剤 |
| DE3725868A1 (de) * | 1986-08-12 | 1988-02-18 | Unilever Nv | Dauerwellshampoo |
| US5077198A (en) * | 1988-04-14 | 1991-12-31 | Eastman Kodak Company | Diagnostic kit and method for rapid detection of antibodies |
-
1996
- 1996-06-06 JP JP9502592A patent/JPH11507918A/ja active Pending
- 1996-06-06 EP EP96920798A patent/EP0837882A1/de not_active Withdrawn
- 1996-06-06 AU AU62228/96A patent/AU6222896A/en not_active Abandoned
- 1996-06-06 WO PCT/EP1996/002453 patent/WO1996041817A1/en not_active Application Discontinuation
- 1996-06-07 ZA ZA9604825A patent/ZA964825B/xx unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9641817A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1996041817A1 (en) | 1996-12-27 |
| AU6222896A (en) | 1997-01-09 |
| JPH11507918A (ja) | 1999-07-13 |
| ZA964825B (en) | 1997-02-13 |
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