WO1996041817A1 - Collagen peptide fraction and its uses - Google Patents
Collagen peptide fraction and its uses Download PDFInfo
- Publication number
- WO1996041817A1 WO1996041817A1 PCT/EP1996/002453 EP9602453W WO9641817A1 WO 1996041817 A1 WO1996041817 A1 WO 1996041817A1 EP 9602453 W EP9602453 W EP 9602453W WO 9641817 A1 WO9641817 A1 WO 9641817A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cpf
- collagen
- collagen peptide
- peptide fraction
- fraction
- Prior art date
Links
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, 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.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU62228/96A AU6222896A (en) | 1995-06-10 | 1996-06-06 | Collagen peptide fraction and its uses |
JP9502592A JPH11507918A (en) | 1995-06-10 | 1996-06-06 | Collagen peptide fraction and its use |
EP96920798A EP0837882A1 (en) | 1995-06-10 | 1996-06-06 | Collagen peptide fraction and its uses |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP95108967 | 1995-06-10 | ||
EP95108967.1 | 1995-06-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996041817A1 true WO1996041817A1 (en) | 1996-12-27 |
Family
ID=8219349
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1996/002453 WO1996041817A1 (en) | 1995-06-10 | 1996-06-06 | Collagen peptide fraction and its uses |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0837882A1 (en) |
JP (1) | JPH11507918A (en) |
AU (1) | AU6222896A (en) |
WO (1) | WO1996041817A1 (en) |
ZA (1) | ZA964825B (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0781779A3 (en) * | 1995-12-27 | 1999-04-07 | Miyagi Kagaku Kogyo Kabushiki Kaisha | Nonantigenic stabilizer and physiologically active substance |
WO2005011740A1 (en) * | 2003-08-05 | 2005-02-10 | Fuji Photo Film B.V. | Use of recombinant or synthetic gelatin-like proteins as stabiliser in lyophilized pharmaceutical compositions |
US8062608B2 (en) * | 2007-05-17 | 2011-11-22 | Advance Dx, Inc. | Fluid separator collection card |
US10088397B2 (en) | 2013-06-19 | 2018-10-02 | Advance Dx, Inc. | Fluid separator collection card assembly |
US10610862B2 (en) | 2016-04-04 | 2020-04-07 | Advance Dx, Inc. | Multiple path sample collection card |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4045289B2 (en) * | 2006-04-12 | 2008-02-13 | 株式会社エーシーバイオテクノロジーズ | Collagen production method and collagen |
JP2010143860A (en) * | 2008-12-19 | 2010-07-01 | Chisso Corp | Protein stabilizer |
JP5803104B2 (en) * | 2010-12-28 | 2015-11-04 | 東ソー株式会社 | Stabilized S-adenosylhomocysteine hydrolase preparation |
JP6319308B2 (en) * | 2012-07-06 | 2018-05-09 | Jnc株式会社 | Aspirin response and reactivity test, and aspirin compliance test using synthetic collagen |
JP6183459B2 (en) * | 2012-08-06 | 2017-08-23 | Jnc株式会社 | Dual antiplatelet / aspirin response and reactivity studies using synthetic collagen |
WO2014025968A2 (en) * | 2012-08-09 | 2014-02-13 | Jnc Corporation | Anti-platelet response and reactivity test using synthetic collagen |
JP2014088409A (en) * | 2013-12-20 | 2014-05-15 | Jnc Corp | Protein stabilizer |
JP2016011310A (en) * | 2015-10-14 | 2016-01-21 | Jnc株式会社 | Protein stabilizer |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH494250A (en) * | 1967-08-31 | 1970-07-31 | Orsymonde | Process for preparing degraded collagen |
US3608083A (en) * | 1968-06-05 | 1971-09-21 | Hoffmann La Roche | Vitamin e powder |
US4307013A (en) * | 1980-10-02 | 1981-12-22 | Nippi, Incorporated | Method for removing antigenicity from peptide |
EP0052374A1 (en) * | 1980-11-18 | 1982-05-26 | Toppan Printing Co., Ltd. | Water based photosensitive composition |
JPS58111661A (en) * | 1981-12-24 | 1983-07-02 | Nippon Kayaku Co Ltd | Preparation of processed cattle meat or fish meat |
GB2112001A (en) * | 1980-01-21 | 1983-07-13 | Seton Co | Trophic agent |
EP0123304A2 (en) * | 1983-04-21 | 1984-10-31 | Asahi Kasei Kogyo Kabushiki Kaisha | A method for stabilizing tissue plasminogen activator and a stable aqueous solution or powder containing the same |
DE3725868A1 (en) * | 1986-08-12 | 1988-02-18 | Unilever Nv | Permanent wave shampoo |
EP0525916A1 (en) * | 1988-04-14 | 1993-02-03 | Johnson & Johnson Clinical Diagnostics, Inc. | Diluent composition |
-
1996
- 1996-06-06 WO PCT/EP1996/002453 patent/WO1996041817A1/en not_active Application Discontinuation
- 1996-06-06 JP JP9502592A patent/JPH11507918A/en active Pending
- 1996-06-06 EP EP96920798A patent/EP0837882A1/en not_active Withdrawn
- 1996-06-06 AU AU62228/96A patent/AU6222896A/en not_active Abandoned
- 1996-06-07 ZA ZA9604825A patent/ZA964825B/en unknown
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH494250A (en) * | 1967-08-31 | 1970-07-31 | Orsymonde | Process for preparing degraded collagen |
US3608083A (en) * | 1968-06-05 | 1971-09-21 | Hoffmann La Roche | Vitamin e powder |
GB2112001A (en) * | 1980-01-21 | 1983-07-13 | Seton Co | Trophic agent |
US4307013A (en) * | 1980-10-02 | 1981-12-22 | Nippi, Incorporated | Method for removing antigenicity from peptide |
EP0052374A1 (en) * | 1980-11-18 | 1982-05-26 | Toppan Printing Co., Ltd. | Water based photosensitive composition |
JPS58111661A (en) * | 1981-12-24 | 1983-07-02 | Nippon Kayaku Co Ltd | Preparation of processed cattle meat or fish meat |
EP0123304A2 (en) * | 1983-04-21 | 1984-10-31 | Asahi Kasei Kogyo Kabushiki Kaisha | A method for stabilizing tissue plasminogen activator and a stable aqueous solution or powder containing the same |
DE3725868A1 (en) * | 1986-08-12 | 1988-02-18 | Unilever Nv | Permanent wave shampoo |
EP0525916A1 (en) * | 1988-04-14 | 1993-02-03 | Johnson & Johnson Clinical Diagnostics, Inc. | Diluent composition |
Non-Patent Citations (1)
Title |
---|
DATABASE WPI Section Ch Week 8332, Derwent World Patents Index; Class D13, AN 83-732159, XP002013591 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0781779A3 (en) * | 1995-12-27 | 1999-04-07 | Miyagi Kagaku Kogyo Kabushiki Kaisha | Nonantigenic stabilizer and physiologically active substance |
WO2005011740A1 (en) * | 2003-08-05 | 2005-02-10 | Fuji Photo Film B.V. | Use of recombinant or synthetic gelatin-like proteins as stabiliser in lyophilized pharmaceutical compositions |
US8062608B2 (en) * | 2007-05-17 | 2011-11-22 | Advance Dx, Inc. | Fluid separator collection card |
US8252139B2 (en) | 2007-05-17 | 2012-08-28 | Advance Dx, Inc. | Method of making a fluid separator collection card |
US10088397B2 (en) | 2013-06-19 | 2018-10-02 | Advance Dx, Inc. | Fluid separator collection card assembly |
US10871428B2 (en) | 2013-06-19 | 2020-12-22 | Advance Dx, Inc. | Method of assembling a fluid separator collection card assembly |
US10610862B2 (en) | 2016-04-04 | 2020-04-07 | Advance Dx, Inc. | Multiple path sample collection card |
Also Published As
Publication number | Publication date |
---|---|
EP0837882A1 (en) | 1998-04-29 |
JPH11507918A (en) | 1999-07-13 |
ZA964825B (en) | 1997-02-13 |
AU6222896A (en) | 1997-01-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5877152A (en) | Method for isolation of highly pure von Willebrand Factor | |
US4824938A (en) | Water-soluble dry solid containing proteinaceous bioactive substance | |
FI85335C (en) | Process for Preparation of Lyophilized Pharmaceutical Tissue Plasma Minogen Activator (t-PA) Composition | |
AU2003234743B2 (en) | Storage-stable, liquid fibrinogen formulation | |
FI85334B (en) | FOERFARANDE FOER FRAMSTAELLNING AV EN VATTENBASERAD, VAEVNADSPLASMINOGENAKTIVATOR (T-PA) INNEHAOLLANDE, KONCENTRERAD PARENTERAD LOESNING. | |
DE3400413C2 (en) | ||
EP0837882A1 (en) | Collagen peptide fraction and its uses | |
JPH0334992A (en) | Stabilized compound containing epidermic growth factor | |
JPH07501517A (en) | topical fibrinogen complex | |
KR20060135761A (en) | Wound dressings comprising a protein polymer and a polyfunctional spacer | |
EP0410207B1 (en) | Stabilization of highly purified proteins | |
WO1992013495A1 (en) | Fibrinogen based adhesive | |
JPH08504407A (en) | Method for preparing a biologically safe biological composition | |
US5798116A (en) | Stabilized materials comprised of copper ion-containing fibronectin mats | |
US8741846B2 (en) | Storage-stable, functionally intact fibrinogen | |
CN112717200A (en) | Recombinant human collagen absorbable hydrogel skin scaffold and preparation method and use method thereof | |
US5091363A (en) | Agent for the therapy of factor viii-resistant hemophilia a, and a process for the preparation thereof | |
JPH06135851A (en) | Chondroitinase composition and preparation for injection containing the same composition | |
EP0691850A1 (en) | Factor xiii for treatment of skin wounds | |
JPH0920677A (en) | Wound-healing agent | |
RU2687102C1 (en) | Pharmaceutical substance for treating infected wounds of various origins | |
JPH04198195A (en) | Method for stabilizing cpb-i and pharmaceutical composition | |
JP2916948B2 (en) | Method for stabilizing CPB-I and its pharmaceutical composition | |
US20020031518A1 (en) | Plasminogen fragment having activity to inhibit tumor metastasis and growth and process for preparing same technical field | |
CA2159609C (en) | Factor xiii for treatment of skin wounds |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AU AZ BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU IL IS JP KE KG KP KR KZ LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG US UZ VN |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 1997 502592 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1996920798 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 1996920798 Country of ref document: EP |
|
NENP | Non-entry into the national phase |
Ref country code: CA |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1996920798 Country of ref document: EP |