WO1999009835A1 - Utilisation d'une composition anti-microbienne - Google Patents
Utilisation d'une composition anti-microbienne Download PDFInfo
- Publication number
- WO1999009835A1 WO1999009835A1 PCT/SE1998/001510 SE9801510W WO9909835A1 WO 1999009835 A1 WO1999009835 A1 WO 1999009835A1 SE 9801510 W SE9801510 W SE 9801510W WO 9909835 A1 WO9909835 A1 WO 9909835A1
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- WO
- WIPO (PCT)
- Prior art keywords
- product
- microbial
- treatment
- use according
- intended
- Prior art date
Links
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Classifications
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- A—HUMAN NECESSITIES
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- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
- A01N63/50—Isolated enzymes; Isolated proteins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
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- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
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- 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
- A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
- A61L17/005—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters containing a biologically active substance, e.g. a medicament or a biocide
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
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- 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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/005—Ingredients of undetermined constitution or reaction products thereof
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- A—HUMAN NECESSITIES
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- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
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- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/005—Ingredients of undetermined constitution or reaction products thereof
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- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- 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
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
Definitions
- the present invention relates to the use of an anti-microbial composition comprising at least one anti-microbially active protein isolated from mussels and carbohydrates for the manufacturing of a product for treatment of tissues, body surfaces and cavities.
- an anti-microbial composition for the manufacturing of a product having an anti-microbial effect and a coagulative effect for anti-microbial treatment of microbially contaminated tissues, e.g. connective tissue, mucous membrane and intestinal tract and for treatment of bleeding and oozing tissue damages.
- microbially contaminated tissues e.g. connective tissue, mucous membrane and intestinal tract and for treatment of bleeding and oozing tissue damages.
- anti-microbial treatment means that the treatment results in neutralisation, inactivation or growth inhibition of at least part of the contaminating microbes and preferably of the pathogenic microbes.
- microbe includes viral structures and toxins. For simplicity reasons the term “cleaning” is in these specifications sometimes used instead of anti-microbial treatment and/or purification.
- Infection Microbes i.e. bacteria, protozoa, rickettsiae, fungi, viruses etc.
- bacteria i.e. bacteria, protozoa, rickettsiae, fungi, viruses etc.
- a series of events is started as soon as the immune system receives enough chemotactic signals from the intruders, by damaged tissue cells and from the first responding immunocells, such as macrophages and leukocytes.
- the symptoms of an ongoing inflammation and/or infection are partly caused by the foreign intruders but also by some of the activated immunocells themselves, for example, cytokines from lymphocytes and contents from lysed cells.
- the immune system is successful in fighting foreign intruders, inflammations and infections but there are a number of reasons for an infection/inflammation going astray, such as temporary or chronic immune deficiencies, diseases, drugs and circulation insufficiencies.
- a common reason for an otherwise functional immune system of not responding is that the microbes may disguise themselves beyond recognition of the immunocells, e.g. they may fold back certain cell surface receptors which are the actual homing sites for immunocells, cover themselves with fibrin, excrete substances that destroy or paralyse the immunocells.
- the formed antibodies are often unable to detect and to home with the viral structure since it is intracellular and the only opportunity the extracellular antibodies have to make contact is in the event the virus changes its host cell. An extremely severe situation is the case where an infection is treated with antibiotics because of a failing immune system and the microbial strain in question develops resistance to the drug - the consequences may easily become disastrous.
- Microbial contamination in the clinical sense can roughly be divided into sub-clinical and clinical infections, respectively.
- Sub-clinical infection indicates that there is a microbial invasion present but not virulent enough to trigger the immune system into any greater action.
- Clinical infection may show one or more of the symptoms of a responding immune system, e.g. inflammation, erythema, oedema, exudation, pus and soreness to different degrees.
- Blood clotting The initial response to a vascular injury is a contraction of the vessel wall smooth muscle, which instantaneously diminishes blood flow from the rupture. Disruption of the endothehal hning of the vessel triggers the formation of a platelet plug, which is a loose aggregation of cells that needs to be reinforced by fibrin into a stable insoluble plug by stimulation of the coagulation cascade. Coagulation results from a series of sequential events involving clotting factors (enzymes), substrates, initiators and inhibitors. Most of the clotting factors exist as zymogens that need to be converted to their activated enzymatic forms during coagulation.
- Activated factor X is involved in one of the final steps of the coagulation by converting protrombin to trombin. There are two pathways that will generate activated Factor X, the extrinsic and the intrinsic pathways.
- the trombin formed cleaves fibrinogen, forming fibrin monomers.
- Factor XIII then catalyses the polymerisation of the monomeiic fibrin into highly cross-Unked and insoluble fibrin that holds the platelet plug firmly in place.
- Tissue healing Tissue healing, e.g. following trauma, burn or post-surgical wound, sometimes lead to excessive scar formations, keloids and tissue adhesions.
- abnormal tissue healing may occur.
- Acute inflammations and/or severe infections cause oedema and swelling of the affected area, which could cause temporary circulation deficiencies preventing the series of events of a healthy healing process.
- Necrotic tissue, pus and blood clots are also obstacles of the natural healing process that can lead to poor healing.
- the natural healing process requires a certain inflammatory response to trigger the mechanisms of the immune system and to initiate the series of events for a proper tissue healing. Disturbances of the process may lead to cosmetically and functionally poor results.
- a polypepti.de fraction has been isolated from bivalve, Tridacna maxima, by
- EP-A-50 636 discloses a specific polypeptide fraction which has been isolated from Mytilus mussels and the use thereof as an anti-microbial drug.
- the fraction in question is characterised as capable of biospecifically binding at least one sialic acid in presence of calcium ions.
- WO 88/04303 describes a lectin, which has been isolated from scallops, Placopecten magellanicus. The lectin binds to certain cell types, such as Gram- negative bacteria.
- the patent claims refer to ways of purification and identification of the lectin and no use is suggested for the product.
- WO 85/05033 describes a crude aqueous extract from Green mussel, Perna canaliculus, which is suggested to be used as a nutritious protein supplement and as an antiphlogistic drug.
- WO 94/04033 describes an anti-microbial composition comprising an antimicrobially active protein isolated from mussels.
- the object of the invention is to provide a product for treatment and cleaning of microbially contaminated human or animal tissues, body surfaces and cavities, including bleeding wounds, lesions and damaged tissues.
- a further object of the invention is to provide a product having a coagulative effect resulting in decreased bleeding time of bleeding wounds and improved tissue healing.
- the present invention relates to the use of such antimicrobial composition for the manufacturing of a product intended for treatment of bleeding wounds, lesions and damaged tissues wherein use is made of the previously known anti- microbial effect and in addition a coagulative effect.
- the mechanism of action of the homing sequence between the proteins and a microbial cell is not yet completely elucidated. Macroscopically, the docking can be observed as a traditional agglutination reaction or as a precipitate. Microscopically, a docked cell is instantly paralysed/neutralised and is unable to multiply. Within two hours morphological changes can be observed and the cell collapses finally and within 36 hours it is completely lysed.
- the docking mechanism between erythrocytes and the mussel protein seems to be identical to the one between microbes and the mussel protein, in macroscopic and microscopic perspectives. It has not yet been identified if the cell surface receptor(s) on erythrocytes is/ are identical to those on microbial cells. From the evolutionary point of view it is though likely that some basic functions may have been maintained when the haemo-lymphatic system was developed into two separate systems, blood and lymph systems, in higher species, and that is a hypothesis why the mussel protein reacts with cell types that are several hundred million years younger than the mussel itself.
- the mussel protein In its present formulation, the mussel protein will have limited systemic function, i.e. direct contact with the blood system. In fact, administration into the blood stream could cause thromboses and emboli. Furthermore, it is not likely that the mussel protein, in high purity, will be very antigenic and cause formation of monoclonal antibodies since the binding to erythrocytes is instantaneous. It is more likely to expect that some interaction can be observed between the mussel protein and already existing antibodies.
- the anti-microbial composition compiising at least one anti-microbially active protein isolated from mussels and carbohydrates, such as glycogen, is used for the manufacturing of a product which can be any product for which it is advantageous having an antimicrobial effect and/or a coagulative effect.
- the anti-microbial compositon is used for the manufacturing of a product for external use such as a plaster, an adhesive dressing, a band aid, a bandage or a dressing.
- the anti-microbial compositon is used for the manufacturing of a product for internal use such as a catheter, an implant, or a suture thread, or a biodegradable of the products mentioned above.
- the extract was pumped on to a DEAE-Sepharose CL6B column which had been equilibrated with 0.10 M NaCl + 50 mM Tris-HCl, pH 7.5, buffer.
- the column was washed with the buffer till UV reached baseline, about two bed volumes and then a gradient salt buffer was introduced, 0.20 - 1.0 M NaCl + 50 mM Tris-HCl, pH 7.5, over 20 bed volumes. All collected fractions were desalted using PD-10 columns and tested for haemo- agglutination with 1% sheep erythrocytes, heparinised. Noticeable, the early fractions from the gradient contained HA-activity as well as fraction collected from regenerating the DEAE- matrix with 4 M NaCl, pH 3. The HA-active fractions were correlated to their anti- microbial activity in a MIC-test using a strain of E. coli and all fractions showing HA-activity also showed growth inhibition of the E. coli strain.
- the active protein obtained showed a molecular weight of approx. 18-20 kDa with a possible dimeric form at approx. 35-38 kDa, this under light reducing conditions, using SDS-PAGE electrophoresis. Under denatured conditions the protein showed a molecular weight of preferable 14-16 kDa and iso-electric focusing showed an i.p. at 4.3-4.8.
- the preparation contains carbohydrates, e.g. glycogen, necessary for the protein to keep its native properties without auto- agglutination. The yield of the protein was approx. 3 g lyophilised powder.
- the lyophilised powder from example 1 was dissolved and diluted in 0.9% saline to final concentrations of 0.005, 0.05 and 0.5 ⁇ g/ ⁇ l respectively.
- Fresh blood from a healthy person was collected and immediately treated as follows: 200 ⁇ l of blood was pipetted onto clean and dry glass slides, as Control 1.
- the lyophilised powder from example 1 was dissolved and diluted in 0.9% saline to final concentrations of 0.005, 0.05 and 0.5 ⁇ g/ ⁇ l respectively.
- Control 1 200 ⁇ l of blood was pipetted onto clean and dry glass slides, as Control 1.
- a stock solution of the lyophilised powder from example 1 was prepared at a concentration of 1 mg/ml and dispensed in aliquots of 0.5 ml and frozen to -20 °C.
- the fabric pad on a soft plaster was soaked with one aliquot and the plaster was put on the side of the trunk of a person. The procedure was repeated twice daily for 21 days. No irritation, rash, inflammation or itching was observed though the skin in contact with the adhesive on the plaster from time to time showed mild maceration.
- Example 5 The identical aliquots from example 4 were used to treat a fresh cut on the index finger, 6 mm long and about 1 mm deep, heavily bleeding. Within 2 minutes after the accidental cut had happened, a soft plaster soaked with 0.5 ml of mussel protein was applied over the wound. The wound was redressed after 5 minutes with a new soft plaster soaked with the mussel protein. Thereafter, the wound was identically redressed three times a day.
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Abstract
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU88950/98A AU8895098A (en) | 1997-08-27 | 1998-08-24 | Use of an anti-microbial composition |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9703085-2 | 1997-08-27 | ||
| SE9703085A SE9703085D0 (sv) | 1997-08-27 | 1997-08-27 | Anti-microbial composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1999009835A1 true WO1999009835A1 (fr) | 1999-03-04 |
Family
ID=20408050
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/SE1998/001510 WO1999009835A1 (fr) | 1997-08-27 | 1998-08-24 | Utilisation d'une composition anti-microbienne |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU8895098A (fr) |
| SE (1) | SE9703085D0 (fr) |
| WO (1) | WO1999009835A1 (fr) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009037571A3 (fr) * | 2007-09-20 | 2010-03-11 | Mike Ehrlich | Matériel d'hémostase contenant des peptides ou des polysaccharides synthétiques |
| CN105617446A (zh) * | 2014-10-30 | 2016-06-01 | 北京纳米能源与系统研究所 | 一种止血复合材料及其制备方法 |
| CN114668889A (zh) * | 2022-03-30 | 2022-06-28 | 绽妍生物科技有限公司 | 一种含有类贻贝粘蛋白的再生修复敷料及其制备方法 |
| CN114848891A (zh) * | 2022-03-22 | 2022-08-05 | 海南德诺海思生物科技有限公司 | 一种含有类贻贝粘蛋白的复配型创面修复敷料及其制备方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1981003124A1 (fr) * | 1980-04-29 | 1981-11-12 | Pharmacia Ab | Fractions polypeptides de moule pour une utilisation medicale |
| WO1985005033A1 (fr) * | 1984-05-01 | 1985-11-21 | Broadbent, James, Meredyth | Extrait de moules stabilise |
| WO1988004303A1 (fr) * | 1986-12-11 | 1988-06-16 | Medicarb Ab | La lectine et procede d'extraction de celle-ci a partir de coquillages |
| WO1994004033A1 (fr) * | 1992-08-17 | 1994-03-03 | Phairson Medical Ab | Composition antimicrobienne |
| WO1997009992A1 (fr) * | 1995-09-11 | 1997-03-20 | J.W. Broadbent Nominees Pty. Ltd. | Extrait lipidique possedant une activite anti-inflammatoire |
-
1997
- 1997-08-27 SE SE9703085A patent/SE9703085D0/xx unknown
-
1998
- 1998-08-24 WO PCT/SE1998/001510 patent/WO1999009835A1/fr active Application Filing
- 1998-08-24 AU AU88950/98A patent/AU8895098A/en not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1981003124A1 (fr) * | 1980-04-29 | 1981-11-12 | Pharmacia Ab | Fractions polypeptides de moule pour une utilisation medicale |
| WO1985005033A1 (fr) * | 1984-05-01 | 1985-11-21 | Broadbent, James, Meredyth | Extrait de moules stabilise |
| WO1988004303A1 (fr) * | 1986-12-11 | 1988-06-16 | Medicarb Ab | La lectine et procede d'extraction de celle-ci a partir de coquillages |
| WO1994004033A1 (fr) * | 1992-08-17 | 1994-03-03 | Phairson Medical Ab | Composition antimicrobienne |
| WO1997009992A1 (fr) * | 1995-09-11 | 1997-03-20 | J.W. Broadbent Nominees Pty. Ltd. | Extrait lipidique possedant une activite anti-inflammatoire |
Non-Patent Citations (1)
| Title |
|---|
| BIOCHEM. J., Volume 175, 1978, BRIAN A. BALDO et al., "Purification and Characterization of a Galactan-Reactive Agglutinin from the Clam Tridacna Maxima (Roeding) and a Study of its Combining Site", pages 467-477. * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009037571A3 (fr) * | 2007-09-20 | 2010-03-11 | Mike Ehrlich | Matériel d'hémostase contenant des peptides ou des polysaccharides synthétiques |
| CN105617446A (zh) * | 2014-10-30 | 2016-06-01 | 北京纳米能源与系统研究所 | 一种止血复合材料及其制备方法 |
| CN105617446B (zh) * | 2014-10-30 | 2019-06-07 | 北京纳米能源与系统研究所 | 一种止血复合材料及其制备方法 |
| CN114848891A (zh) * | 2022-03-22 | 2022-08-05 | 海南德诺海思生物科技有限公司 | 一种含有类贻贝粘蛋白的复配型创面修复敷料及其制备方法 |
| CN114668889A (zh) * | 2022-03-30 | 2022-06-28 | 绽妍生物科技有限公司 | 一种含有类贻贝粘蛋白的再生修复敷料及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| SE9703085D0 (sv) | 1997-08-27 |
| AU8895098A (en) | 1999-03-16 |
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