WO2000000180A1 - Verwendung von wachstumsfaktoren zur arzneimittelherstellung - Google Patents
Verwendung von wachstumsfaktoren zur arzneimittelherstellung Download PDFInfo
- Publication number
- WO2000000180A1 WO2000000180A1 PCT/CH1999/000278 CH9900278W WO0000180A1 WO 2000000180 A1 WO2000000180 A1 WO 2000000180A1 CH 9900278 W CH9900278 W CH 9900278W WO 0000180 A1 WO0000180 A1 WO 0000180A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- growth factors
- medicament
- medicament according
- insulin
- growth
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/106—Fibrin; Fibrinogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0019—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Definitions
- the present invention relates to the use of growth factors for the manufacture of a medicament for local use in the treatment of fixed bone fractures according to claim 1.
- the external fixation of fractures essentially entails the same problems as described above for fixation by means of implants.
- fixators 3 After initial rigid fixation, dynamization can take place, and a certain preload can be exerted on the fracture area F a . This avoids the bone loss caused by the rigid fixation during fracture healing.
- the areas F f between the bulwark see screws 31, 32, 33, 34 are practically not affected by the bone degradation owing to the possibility of dynamization and the use of the fixator 3 for a very limited time.
- This object is achieved by a medicament for local use in the treatment of bone fractures with internal or external fixation of the fracture parts to one another, which has the features of claim 1 and solved a use of growth factors for the manufacture of a medicament for local use in the treatment of fixed fractures.
- GFs growth factors
- Soluble low molecular weight proteins such as insulin-like growth factors (IGFs) have long been known for their local effects on the growth of cartilage and bone (Canalis, E. and LG Raisz, Endocr. Rev. 4: 62-77, 1983) known. The same authors demonstrated a positive effect of IGF on bone DNA synthesis in periosteal and non-periosteal bone.
- IGFs insulin-like growth factors
- IGF-1 In degenerative joint diseases, local application of IGF-1 to stimulate osteoblast activity and collagen production has been postulated.
- An advantage of using IGF in wound and fracture treatment is that IGF has no known relationship to oncogenes.
- IGF-1 also known as Somatomedin C
- Somatomedin C is a basic polypeptide consisting of 70 amino acids and has a molecular weight of 7649 D.
- IGF-1 stimulates inter alia the incorporation of proteoglycan into cartilage by chondrocytes (Froger-Graillard et al., Endocrinology 124: 2365-2372, 1989) and also the synthesis of DNA, RNA and proteins.
- the slightly acidic polypeptide IGF-2 consists like IGF-
- IGF 2 consists of 67 amino acids. IGFs are primarily dependent on growth hormone (somatotropin; GH). IGF-1 is predominantly active in adults, while IGF-2 is the main growth factor in the fetus.
- somatotropin somatotropin
- BMP Bone Morphogenetic Protein
- hOP-1 human Osteogenetic Protein-1
- BMP-7 three-dimensional structure of osteogenic protein 1 (OPl; BMP-7), which can induce bone formation in vivo.
- BMP-4 and BMP-7 are available as recombinant proteins from the BMPs which are members of the TGF beta superfamily.
- recombinant BMPs appear to be able to induce osteogenesis in vivo only if they are bound to suitable carriers or carriers (E. Tsuruga et al., J. Biochem. 121: 317-324, 1997).
- suitable carriers or carriers E. Tsuruga et al., J. Biochem. 121: 317-324, 1997.
- rhBMP-2 recombinant human BMP-2
- suitable carrier materials to accelerate and ensure the healing of bone defects (20 mm long critical-sized defects in the radius of rabbits was described by Zegzula, HD et al. tested and described in the Journal of Bone ans Joint Surgery, 79-A (12) 1778-1790, 1990.
- the carrier material cylinders made of porous polylactide are intended to serve as placeholders and scaffolds for the newly formed bone tissue.
- the collagen claimed in EP-A 0 206 801 has a very good tissue affinity and acts as a carrier material for BMP in the form of ribbons or solid bodies.
- these collagen preparations have a certain inherent antigenic effect, which is probably attributable to the telopeptides present and which disrupt ectopic bone formation.
- the increase in bone stability is a dynamic process that is expressed in a sigmoid curve.
- the osteosynthesis implant or external fixation can usually be removed when the stability of the fracture area has reached a certain threshold.
- Figure 3 shows the hypothetical course of fracture healing using only an osteosynthesis implant or external fixation.
- the implant / fixation must be able to take over the full mechanical load at time 0 and can only be removed when the increase in the stability of the healing bone tissue (plus a certain mechanical stability reserve) can bear these loads again.
- the implant / fixation has to fix the bone fragments in a certain relative position to one another until the bone material newly formed between them can take over this function again, the mechanical loads that act on the broken bone, however, must last from stabilization until the healing bone has regained such a high percentage of its mechanical properties that no additional stabilization is required. This does not mean that the bone has already regained its full mechanical strength when the external stabilization is removed. got to. All methods have in common that the affected area is immobilized for a long time, and next. the already mentioned bone loss the reduced muscle activity leads to muscle loss and a deterioration in mobility. Around to achieve again, time and cost-intensive therapies have to be carried out after removing the external stabilizing agents.
- the growth factors (GF) that can be used in the present invention come from the group of epidermal growth factors (EGF) or insulin growth factors (IGF) or transforming growth factors beta (TGF-beta) or fibrobalast growth factors (FGF). Suitable combinations of two or more of them can of course also be used. Many of the above growth factors are commercially available as lyophilized powders.
- the growth factors are in an injectable formulation. This makes it possible to inject the growth factors directly into the fracture area or m its immediate vicinity and m the rigidly fixed areas F on the bone.
- the growth factors are bound to a suitable biodegradable carrier material or encapsulated in one.
- the size of the individual carrier material particles or the capsules is dimensioned so that the ability to inject is retained.
- the particles or capsules loaded with growth factors can in turn be suspended in auxiliary liquids or gels that improve their ability to inject.
- the growth factors are converted into the following formulations:
- Encapsulated or embedded in biodegradable polymer material wherein the growth factors can be encapsulated in micro- or nanocapsules, made of a suitable biodegradable material such as polylactide, for example by means of "in water drying" of w / o / w emulsions.
- Solid microspheres can be made from one GF-polymer-solvent mixture can be produced, for example, by means of “spray drying”.
- FIG. 3 shows schematically the healing process of a fracture in conventional therapy using only a fixation and using the medicament according to the invention.
- the solid line shows on the one hand the accelerated temporal course of the new bone formation, respectively the increase in the mechanical strength of the healing bone in the fracture area F a .
- the slower increase without using growth factors is shown with the dashed line.
- the fracture must still be provided with a fixation at time 0, which can take over the full mechanical load, but since this only has to be carried for a much shorter period of time, the fixation can be removed much earlier.
- the substantial reduction ( ⁇ t) in the time that the external or internal stabilizing agents have to be worn also reduces the time in which bone material is broken down in the rigidly fixed areas.
- the medicament according to the invention was applied only in the fracture area, the quicker healing of the fracture and the earlier removal of the fixation would have been enough in turn, an earlier resumption of the movement of the affected area reduces a very decisive effect on reducing the duration of the illness and also on the time and financial expenditure required for the after-treatment.
- the growth factors according to the present invention are also injected into the rigidly fixed regions F, F f on the bone, they directly counteract the breakdown of bone material here.
- the medicine may also be injected retrospectively, even in cases where the implants remain in the patient.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physical Education & Sports Medicine (AREA)
- Materials Engineering (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Surgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99926216A EP1091730A1 (de) | 1998-06-29 | 1999-06-29 | Verwendung von wachstumsfaktoren zur arzneimittelherstellung |
AU43562/99A AU4356299A (en) | 1998-06-29 | 1999-06-29 | Utilization of growth factors for the production of medicaments |
JP2000556765A JP2002519317A (ja) | 1998-06-29 | 1999-06-29 | 薬剤製造のための成長因子の使用 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH137598 | 1998-06-29 | ||
CH1375/98 | 1998-06-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000000180A1 true WO2000000180A1 (de) | 2000-01-06 |
Family
ID=4208961
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CH1999/000278 WO2000000180A1 (de) | 1998-06-29 | 1999-06-29 | Verwendung von wachstumsfaktoren zur arzneimittelherstellung |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1091730A1 (de) |
JP (1) | JP2002519317A (de) |
AU (1) | AU4356299A (de) |
WO (1) | WO2000000180A1 (de) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001058426A1 (en) * | 2000-02-09 | 2001-08-16 | White Spot Ag | Sustained release composition comprising insuline like growth factor |
KR100720052B1 (ko) | 2005-10-07 | 2007-05-18 | (주) 차바이오텍 | 성장인자를 함유한 나노입자가 코팅된 연골 조직 재건 및재생을 위한 마이크로스피어 또는 마이크로비드 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4843797B2 (ja) * | 2006-01-18 | 2011-12-21 | 国立大学法人 東京医科歯科大学 | 骨形成促進物質とナノゲルを含有する骨形成用生体材料 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996020698A2 (en) * | 1995-01-05 | 1996-07-11 | The Board Of Regents Acting For And On Behalf Of The University Of Michigan | Surface-modified nanoparticles and method of making and using same |
WO1998043664A1 (en) * | 1997-04-01 | 1998-10-08 | Lg Chemical Limited | Sustained-release composition of drugs encapsulated in microparticles of hyaluronic acid |
WO1998046289A1 (de) * | 1997-04-16 | 1998-10-22 | White Spot Ag | Biodegradables osteosynthese-implantat |
EP0896825A1 (de) * | 1997-08-14 | 1999-02-17 | Sulzer Innotec Ag | Zusammensetzung und Vorrichtung zur Reparatur von Knorpelgewebe in vivo bestehend aus Nanokapseln mit osteoinduktiven und/oder chondroinduktiven Faktoren |
-
1999
- 1999-06-29 EP EP99926216A patent/EP1091730A1/de not_active Withdrawn
- 1999-06-29 JP JP2000556765A patent/JP2002519317A/ja active Pending
- 1999-06-29 AU AU43562/99A patent/AU4356299A/en not_active Abandoned
- 1999-06-29 WO PCT/CH1999/000278 patent/WO2000000180A1/de not_active Application Discontinuation
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996020698A2 (en) * | 1995-01-05 | 1996-07-11 | The Board Of Regents Acting For And On Behalf Of The University Of Michigan | Surface-modified nanoparticles and method of making and using same |
WO1998043664A1 (en) * | 1997-04-01 | 1998-10-08 | Lg Chemical Limited | Sustained-release composition of drugs encapsulated in microparticles of hyaluronic acid |
WO1998046289A1 (de) * | 1997-04-16 | 1998-10-22 | White Spot Ag | Biodegradables osteosynthese-implantat |
EP0896825A1 (de) * | 1997-08-14 | 1999-02-17 | Sulzer Innotec Ag | Zusammensetzung und Vorrichtung zur Reparatur von Knorpelgewebe in vivo bestehend aus Nanokapseln mit osteoinduktiven und/oder chondroinduktiven Faktoren |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001058426A1 (en) * | 2000-02-09 | 2001-08-16 | White Spot Ag | Sustained release composition comprising insuline like growth factor |
KR100720052B1 (ko) | 2005-10-07 | 2007-05-18 | (주) 차바이오텍 | 성장인자를 함유한 나노입자가 코팅된 연골 조직 재건 및재생을 위한 마이크로스피어 또는 마이크로비드 |
Also Published As
Publication number | Publication date |
---|---|
JP2002519317A (ja) | 2002-07-02 |
EP1091730A1 (de) | 2001-04-18 |
AU4356299A (en) | 2000-01-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0980273A1 (de) | Biodegradables osteosynthese-implantat | |
DE69432596T2 (de) | Zusammensetzungen für verabreichung von osteogenen proteinen | |
Bax et al. | Bone morphogenetic protein-2 increases the rate of callus formation after fracture of the rabbit tibia | |
Logan et al. | Transforming growth factor-ß1 and basic fibroblast growth factor in the injured CNS | |
US9717823B2 (en) | Osteogenic cell delivery matrix | |
US8475824B2 (en) | Resorbable matrix having elongated particles | |
DE69632790T2 (de) | Zusammensetzungen unter verwendung von morphogenen proteinen und stimulationsfaktoren | |
DE69434122T2 (de) | Osteogenisches produkt und verwendung | |
Kim et al. | Role of BMP, βig-h3, and chitosan in early bony consolidation in distraction osteogenesis in a dog model | |
DE60101339T2 (de) | Stimulierung des knochenwachstums mit peptidderivaten von thrombin | |
Mandracchia et al. | Current concepts of bone healing | |
US10363238B2 (en) | Methods and compositions to enhance bone growth comprising a statin | |
DE60016614T2 (de) | Zusammensetzungen zur abgabe osteogener proteine | |
WO2000047114A1 (en) | Injectable collagen-based delivery system for bone morphogenic proteins | |
US20100226959A1 (en) | Matrix that prolongs growth factor release | |
JP2018517527A (ja) | オキシステロールを含有するインプラントおよびその使用方法 | |
Bernstein et al. | Can bone healing in distraction osteogenesis be accelerated by local application of IGF‐1 and TGF‐β1? | |
Kitasato et al. | Local application of alendronate controls bone formation and β‐tricalcium phosphate resorption induced by recombinant human bone morphogenetic protein‐2 | |
Park et al. | Interaction between active motion and exogenous transforming growth factor Beta during tibial fracture repair | |
WO2000000180A1 (de) | Verwendung von wachstumsfaktoren zur arzneimittelherstellung | |
AU2008247320B2 (en) | A method for treating inflammation and controlled-release material capable of providing same | |
US5830857A (en) | Method of treating epilepsy | |
DE102005034421A1 (de) | Bioresorbierbares mineralisiertes Material zur Füllung von Knochendefekten | |
DE102007012276A1 (de) | Zusammensetzung zur Behandlung von Knochen- und/oder Knorpeldefekten | |
Gradinger et al. | Bioaktive Oberflächenbeschichtung |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1999926216 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09720626 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 556765 Kind code of ref document: A Format of ref document f/p: F |
|
WWP | Wipo information: published in national office |
Ref document number: 1999926216 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
NENP | Non-entry into the national phase |
Ref country code: CA |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1999926216 Country of ref document: EP |