CN1744819A - Reduction of reactive oxygen species in chronic wound care - Google Patents
Reduction of reactive oxygen species in chronic wound care Download PDFInfo
- Publication number
- CN1744819A CN1744819A CNA2003801095668A CN200380109566A CN1744819A CN 1744819 A CN1744819 A CN 1744819A CN A2003801095668 A CNA2003801095668 A CN A2003801095668A CN 200380109566 A CN200380109566 A CN 200380109566A CN 1744819 A CN1744819 A CN 1744819A
- Authority
- CN
- China
- Prior art keywords
- solution
- ion
- wound
- value
- weight
- 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.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/32—Manganese; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
Reactive oxygen species associated with a wound are modulated through treatment of the wound with a solution of metal ions selected from the group consisting of potassium ions, zinc ions, calcium ions and rubidium ions, at a pH of between about 5 and about 7. Preferably, citric acid is employed to adjust the pH of the solution. Application of the extract to a wound exhibiting superoxide anions has been found to be effective in the treatment of these wounds through the reduction of the level of superoxide anions. Moreover, treatment of partial thickness excision wounds as well as contact burn wounds with the present composition has been found to improve epithelialization of these wounds. In addition to the antioxidant activity of the present invention, treatment of the wound employing the present composition produces inhibitory effects on ROS production by human PMNs and on human complement activation, and therefore, is further beneficial in chronic wound management.
Description
The intersection application case
The application's case is the non-provisional application case of the priority of No. the 60/436th, 197, the provisional application case of advocating application on December 23rd, 2002.
About the research of federal government's patronage or the statement of development
Inapplicable
Technical field
The present invention relates to the nursing of wound, relate in particular to chronic (non-reacted) wound that character is bedsore, burn etc.
Background technology
In recent years, apparent free radical is played an important role in the wound healing that is damaged.In local and chronic wounds, known free radical causes cell damage and serve as inhibiting factor in agglutination.In chronic wounds, ischemic conditions can be transformed into the enzyme hypoxanthine dehydrase xanthine oxidase of Catalytic Oxygen to the transformation of superoxide anion.By stimulating polymorphonuclear neutrophisls (PMN) in wound, to produce superoxide anion.Superoxide anion is for to organizing virose free radical, and it produces the formation that also can cause comprising more virose hydroxyl and stronger hypochlorous other reactive oxygen species of non-free oxidant (ROS).By nitrogen oxide, the free radical that is produced by macrophage (another inflammatory cell in the wound) superoxide anion is easy to react and forms the peroxynitrite root that surrounding tissue is played adverse effect.At last, superoxide anion also can bring out the crosslinked of substrate molecule cellulose and fibronectin, thereby causes not too being fit to the conversion matrix of epithelial growth.
Summary of the invention
According to an aspect of the present invention, after synthetic composition treatment with metal ion, the reactive oxygen species that modulation is associated with wound.Find, apply described composition to the wound that shows superoxide anion and effectively treat and these wounds that heal by the level that reduces the superoxide anion that is associated with wound.The present invention is especially effective in the treatment of chronic wounds and healing.And, found that the epithelium of having improved these wounds with present composition treatment segment thickness incised injury and contact burn forms.
Except that antioxidation activity of the present invention, adopt the present composition to treat described wound and will the generation to R0S produce depression effect, and human complement is activated the generation depression effect, and therefore further be of value to the nursing of chronic wounds by human PMN.
Description of drawings
Fig. 1 is as is checked the figure of the IC50 value of determined natural oak bark extract and synthetic solvent of the present invention to compare by the superoxide anion scavenger;
Fig. 2 is as is checked the figure of the IC50 value of determined natural oak bark extract and synthetic solvent of the present invention to compare by chemiluminescence; With
Fig. 3 is as is checked the figure of the IC50 value of determined natural oak bark extract of classical pathway and synthetic solvent of the present invention to compare by complement.
Embodiment
The technology used in the present invention and method
Material
A kind ofly be applicable to that preferred composition of the present invention comprises the calcium ion of the zinc ion of the potassium ion of 10-80 weight portion, 0.00001-20 weight portion, 0.01-10 weight portion and the quantity rubidium ion I up to 40 weight portions, the pH value of described solution is between about 5 and about 7.In one embodiment, described metal ion comprises (for example) chloride, sulphate, citrate, hydroxide derived from its salt separately.As required, preferably by adding the adjusting that citric acid is realized the pH value of described composition to described solution.For the object of the invention, this composition is sometimes referred to as PHI5 (using citric acid pH value to be adjusted to 5 polyhydrate electrolyte) in this article.
Found to use potassium, zinc and the rubidium ion therapeutic value of (not comprising calcium).Yet calcium is applicable to the treatment of some type wound, even and be not pharmaceutically effective to special wound, when the described special wound of treatment, it is present in, and curative effect to preferred solution is harmless in the solution of the present invention.
Suppress the check (chemiluminescence check) that ROS produces by human neutrophil
(Bloedbank Midden-Nederland, Utrecht isolate polymorphonuclear neutrophisls (PMN) in venous blood TheNetherlands) from the healthy volunteer.In white 96-hole flat-bottom microtiter plates (Costar, Badhoevedorp, The Netherlands), final volume 50 μ L are arrived in the sample serial dilution.In every hole, add 50 μ L PMN suspension (1 * 107 cells/ml) and 50 μ L luminols (120 μ M).By adding the zymosan A (OPZ of 50 μ L conditioning; Ultimate density: 200 μ g/mL) trigger PMN.During 30min, use Titertek Luminoskan photometer (TechGen International, ZelUk, Belgium) the luminous 0.5sec of every 2min monitoring chemical.
The activity that peak level is used for calculating the relevant sample of corresponding control group with it (the identical cultivation under the no sample situation).In the Hank balanced salt solution (I-IBSS) that is buffered to pH 7.35 with NaHCO3 and replenishes, carry out experiment, to avoid cell aggregation (HBSS-gel) with 0.1% (w/v) gel.Obtain OPZ by under 37 ℃, cultivating washed commercial zymosan A 30min with the human pooled serum (HPS) of dilution in 1: 10.After the washing, the product through nursing one's health is suspension (ultimate density: 0.8mg/mL) in HBSS again.
Superoxide anion is removed check
In the flat-bottom microtiter plates of white 96-hole, with phosphate buffer (PBS; PH 7.4) final volume 50 μ L are arrived in the sample serial dilution.Subsequently, add hypoxanthine (50 μ L; Ultimate density 1mM) and buffer or Sudismase (SOD; 25 μ L; 10U/mL).Introduce superoxide anion-O2 (free radical product) by the xanthine oxidase (10mU/mL) that adds 25 μ L, and during 15min, use Fluoroskan Ascent FL photometer (Labsystems, Breda, TheNetherlands) every millimeter luminous 0.5sec of monitoring chemical.Can suppress the activity that part is calculated described test compounds from the SOD-of described chemiluminescence signal.For getting rid of the direct influence of sample, determine the formation of uric acid on 290nm spectrophotometric ground to xanthine oxidase activity.
The haemolysis check (classical pathway and alternative route) of human complement activity
By people such as Klerx (Klerx, J.P.A.M., Beukelman, C.J., Van Dijk, people such as H., Microassay for colorimetric estimation of complement activityin guinea pig, human and mouse serum.J.Immunlol Methods 1983,63:215-220) described trace check revision determines that sample is to the tradition of human body complement and the inhibition activity of alternative route (being respectively CP and AP).At U type hole microtiter plate (GreinerLabortechnik, Nortingen, Germany) in, sample series being diluted in (1) adds to the VSB-CP of final volume 50 μ l (CP) with 0.15mM Ca2+ and 0.5mM Mg2+ (veronal (Veronal) brine buffer solution is with 5mM veronal, 150mM prepared in saline; PH 7.35), or (2) are with the preparation of above-mentioned veronal brine buffer solution and add to 0.5m Mg2+ and 0.8mM EGTA among the VSB-AP of final volume 100 μ l (AP).Subsequently, add 50 μ l (CP) or the human pooled serum (HPS of 25 μ l (AP); Obtain from healthy supplier) suitable dilution, and described plate cultivated 30min down at 37 ℃.Add 50 μ l sensitization sheep erythrocyte (CP) or 25 μ l rabbit erythrocyte (seeing below) afterwards, under 37 ℃, described plate is being cultivated 1h again.The sheep or the rabbit blood that are stored in the A Shi solution (Alsever solution) are erythrocytic sources.Before using, erythrocyte is washed three times with salt solution.The sheep erythrocyte is by cultivating 10min and sensitization with dilution hemolysin (1: 800); After the washing, described erythrocyte through sensitization is resuspended among the VSB-CP (4 * 108 cells/ml).The rabbit erythrocyte is suspended in (3 * 108 cells/ml) among the VSB-AP.At last, (900xg 5min) so that the rotation of complete cell and fragment settles down, and transfers to the 96-hole flat-bottom microtiter plates that 200 μ l water are contained in each hole with 50 μ l supernatants with described microtiter plate centrifugation.In the plate of back, uses above-mentioned automatic ELISA reader of under 405nm, working with spectrophotometry measurement by hemoglobin content that globulolysis was discharged.Control group by with water (100% haemolysis) or buffer solution (VSB-CP or VSB-AP; 0% haemolysis) cultivate together through the erythrocyte supernatant of similar processing and wherein HPS by hot deactivation HPS (56 ℃, 30min; The background colour of check sample) culture that replaces is formed.
Determine cytotoxicity
Acetone stock solution (the CFDA of preparation 5-carboxyl oxalic acid luciferin; 10mg/ml) and at-20 ℃ store down.Before the use, it is 1: 1000 with described stock solution dilution with buffer.Dissolving propidium iodide (PI in the phosphate buffer (PBS) of 10ml; 1.5mg), described phosphate buffer (PBS) contains 2.5% quenching ink (quenching ink), 5%w/v EDTA and 8mg bovine serum albumin(BSA) (BSA).Also in buffer, suspend again with vital stain CFDA (10 μ g/ml) mark PMN15min, washing at 20 ℃, to reach the concentration of 107 cells/mL.Dilute sample with equal volume under 37 ℃ is cultivated 15min with the described cell suspension of 100 μ l.Subsequently, with 25 μ l PI/ink solution washings and the described cell that dyes with discrimination between viable (green fluorescence) and dead cell (red fluorescence).(Wetzlar Germany) determines the percentage of dead cell for Fluovert, Leitz to use fluorescence microscope.
Result and discussion
The reactive oxygen species that is associated with wound produces can come from some potential sources.Solution of the present invention shows that the generation to the reactive oxygen species (ROS) that is associated with described wound has pharmaceutically effectively depression effect.
ROS reactive oxygen species of serving as reasons and be excited human polymorphonuclear neutrophisls (PMN) generation in the source in the wound.Raise to (for example) wound site and the PMN that is activated and will consume the oxygen that is changed into ROS in a large number.The processing that is known as respiratory burst is depended on and can be handled the enzyme nadph oxidase that activates by receptor-mediated and acceptor dependent/non-dependent.Typical acceptor dependent stimulation thing is (for example) complement component C5a and C3b, the chemotaxis tripeptides fMLP of bacterial derivation and the zymosan of conditioning; Acceptor dependent/non-dependent stimulus comprises long-chain unsaturated fatty acid.According to the activation of PMN, the multicomponent nadph oxidase is integrated in the cell membrane.Subsequently, described oxidase will be transferred to the molecular oxygen (molecular oxygen) of described film opposite side from the electronics of the NADPH of film cytosol side.This causes containing generation in ingested microorganisms (in the born of the same parents) phagosome or the superoxide anion (02) that born of the same parents are outer.Formed most of superoxide anion is transformed into hydrogen peroxide (H2O2).The latter only has microbe killing properties when high concentration, and superoxide anion is because its limited membrane permeability self can not killing bacteria.Some hydrogen peroxide are changed into the hydroxyl that has activity by iron catalysis Fenton reaction.Yet hydrogen peroxide is transformed into hypochlorous acid (HOCL) mostly, and known most bactericidal properties oxidant produces by PMN.Back one transformation takes place under the situation that has halogen (chloride) ion, and by myeloperoxidase (MPO) (a kind of also by being excited the enzyme that PMN discharged) catalysis.Although in phagolysosome, in order to the bacterium and the prevent wound infection of kill ingested, the outer generation of the born of the same parents of these oxygen metabolism things has adverse effect to surrounding tissue to the ROS in the born of the same parents (together with soluble protein and other cytotoxin enzyme of discharging from lysosome (particle)).
Except that above-mentioned ROS, also notice the nitrogen oxide (NO) that produces by the macrophage that is present in the wound.Described radical nitric oxide can easily be reacted with superoxide anion, and it causes the formation of peroxynitrite root (ONOO), and described peroxynitrite root is a kind of effective, metastable oxidant that is similar to hydroxyl (seeing above) characteristic that has.
Consider by being excited the ROS inhibitory action of human PMN, adopt chemiluminescence to verify as PHI5 the IC50 value is defined as 12 ± 2ml/ml.(described IC50 value is the sample concentration in given 50% inhibiting test macro; Mean value ± the SD (standard deviation) that determines that the IC50 value representation obtains with two crowdes of PMN from two different donors).Owing to the depression effect of ROS product in check can be caused by cell death, therefore also investigated the cytotoxic effect of described sample.Residue PMN is mark and cultivate with PHI5 with vital stain CFDA (5-carboxyl oxalic acid luciferin).Subsequently, give dead cell stain with propidium iodide.Found to compare, PMN has not been had any cytotoxic effect with the cultivation that 100 μ l/ml PHI5 carry out with control cells.Deduction with the inhibitory action of the ROS product of PHI5 not owing to cytotoxic effect to PMN.
Except that as mentioned above by being excited the superoxide anion that PMN produced, these free radicals also can result from the chronic wounds, but can change described enzyme hypoxanthine dehydrase into xanthine oxidase that Catalytic Oxygen is transformed into superoxide anion in described chronic wounds place ischemic conditions.Therefore, comprise that removing is regarded as being of value to treatment chronic wounds by PMN or the antioxidation activity by the superoxide anion that xanthine oxidase produced.PHI5 is shown as the significant scavenger of superoxide anion, and this mainly is owing to there is the event of citric acid.
Inhibitory action seen in ROS generation check (seeing above) also can produce by the specific removing of superoxide anion.Reported that oak bark extract (OBE) directly influences the effect of PMN.Viewed as removing in the check at the superoxide anion that adopts PHI5 (IC50 12 μ l/ml), active increase most likely by the citric acid component by PHI5 to due to the extra removing of superoxide anion.Therefore, PHI5 can provide superoxide anion to remove and to these two kinds of effects of inhibition that ROS produces, promote the serviceability of the present invention in wound care (especially chronic wounds nursing) whereby.
In the haemolysis check, also tested the regulating action of PHI5 to complement activity.Complement system is the immune part of non-habitual body fluid and plays an important role in human defense mechanism.Complement system comprises 20 multiple proteins, comprises complement component C 1 to C9.By tradition, substitute or the complement activation effect of lectin approach can cause continuous complement protein to dissociate with similar cascade system generation soluble protein, this finally can cause causing the formation of the macromolecule membrane attack complex (MAC) of bacterium death (or cause external source red blood cell death by dissolving).In addition, also can produce the little cleavage product that to regulate a lot of immunomodulatory effects.In this regard, complement factor C3b has main biological function, this is because (cause of disease) microorganism and foreign cell (zymosan) are covered (opsonification) by C3b, and this makes the phagocyte (for example PMN) that has C3b receptor on its film can discern and eat these invadors and destroy described invador by generation ROS.Segment C5a is another activator of PMN; In addition, it still is these cytophagous main chemotactic factor.
The inhibitory action of complement activation has limited the generation as the complement cleavage product of C5a.As above summarize, this will cause PMN in the wound still less inflow and the wound of reduction in the stimulation of PMN, and the born of the same parents that therefore reduce ROS and peroxynitrite root form outward, and therefore reduce tissue damage.
(for example, MMP), PHI5 suppresses human complement via described classical pathway and activates, and suppresses the generation of ROS by the PMN that is activated although other factor of control wound healing may be also very important.In addition, found that the citric acid that is associated with PHI5 helps to remove superoxide anion.The minimizing of ROS level helps the beneficial effect seen in the wound care (especially chronic wounds nursing), and preparation contains the metal ion and the citric acid of the present composition.
Fig. 1-3 is the IC-50 value of oak bark extract of prior art and the comparison of synthetic composition of the present invention, its for describe as superoxide anion scavenger check (Fig. 1), chemiluminescence check (Fig. 2) and complement check in the classical pathway (Fig. 3) determined as described in the figure of IC50 value of two kinds of compositions.Referring to these figures, it shows about super oxygen removing and PMN inhibition (chemiluminescence check) PHI5 more effective than natural oak bark extract (OBE), and only effective not as natural oak bark extract (OBE) slightly about the modulation PHI5 of complement activity.
Claims (15)
1. method that is used to promote wound healing, it comprises the steps:
It is the neutral metal ion aqueous solution substantially that pharmaceutically effective pH value is provided, described metal ion is selected from the group that is made up of potassium ion, zinc ion, calcium ion and rubidium ion, described solution is applied to described wound through one period that enough makes the reactive oxygen species that is associated with described wound reach neutralization, promotes the healing of described wound whereby by the described neutralization of the described solution pair described reactive oxygen species that is associated with described wound.
2. method according to claim 1, it comprises the step of regulating the described pH value of described solution with citric acid.
3. method according to claim 2, the described pH value of wherein said solution is about 5 and about 7.
4. method according to claim 1, wherein said solution show that one is about the super oxygen removing IC50 value of 33/ml.
5. method that is used to promote wound healing, it comprises the steps:
The pharmaceutically effective metal ion aqueous solution of pH value between about 5 and about 7 is provided, described metal ion is selected from the group that is made up of potassium ion, zinc ion, calcium ion and rubidium ion, described solution is applied to described wound, described whereby solution by be excited polymorphonuclear neutrophisls suppress the reactive oxygen species that is associated with described wound generation, remove superoxide anion, suppress to attract or stimulate the factor of polymorphonuclear neutrophisls or reach the combination of described effect, and described wound healing.
6. method according to claim 5 wherein adopts citric acid that the described pH value of described solution is adjusted to about 5.
7. method according to claim 5 wherein adopts hydrochloric acid that the described pH value of described solution is adjusted to about 7.
8. method according to claim 1, wherein said solution comprise the potassium ion of 10 to 20 parts by weight, the zinc ion of 0.00001 to 20 parts by weight and the rubidium ion that quantity is no more than about 40 parts by weight.
9. method according to claim 8, wherein said solution contain enough citric acids and are adjusted between about 5 and 7 with the described pH value with described solution.
10. method according to claim 8 comprises the calcium ion of 0.01 to 10 parts by weight.
11. containing enough citric acids, method according to claim 10, wherein said solution be adjusted between about 5 and 7 with described pH value with described solution.
12. method according to claim 5, wherein said solution comprise the potassium ion of 10 to 20 parts by weight, the zinc ion of 0.00001 to 20 parts by weight and the rubidium ion that quantity is no more than about 40 parts by weight.
13. containing enough citric acids, method according to claim 12, wherein said solution be adjusted between about 5 and about 7 with described pH value with described solution.
14. method according to claim 5 comprises the calcium ion of 0.01 to 10 parts by weight.
15. containing enough citric acids, method according to claim 5, wherein said solution be adjusted between about 5 and about 7 with described pH value with described solution.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43619702P | 2002-12-23 | 2002-12-23 | |
| US60/436,197 | 2002-12-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1744819A true CN1744819A (en) | 2006-03-08 |
Family
ID=32682357
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2003801095668A Pending CN1744819A (en) | 2002-12-23 | 2003-12-23 | Reduction of reactive oxygen species in chronic wound care |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1575359A4 (en) |
| JP (1) | JP2006511585A (en) |
| CN (1) | CN1744819A (en) |
| AU (1) | AU2003303335A1 (en) |
| CA (1) | CA2511440A1 (en) |
| WO (1) | WO2004057965A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6227856B2 (en) * | 2008-04-01 | 2017-11-08 | アントイポデアン ファーマシューティカルズ， インコーポレイテッド | Composition and method for skin care |
| WO2011022757A1 (en) * | 2009-08-24 | 2011-03-03 | Queensland University Of Technology | Purine-targeted diagnosis and therapy of wounds |
| WO2013016255A1 (en) * | 2011-07-28 | 2013-01-31 | 3M Innovative Properties Company | Wound-healing compositions and method of use |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3416777C2 (en) * | 1984-05-07 | 1986-11-20 | Gödecke AG, 1000 Berlin | Topical pharmaceutical preparations |
| WO1994011010A2 (en) * | 1992-11-06 | 1994-05-26 | H.E. Stanley Pharmaceuticals, Inc. | Compositions of oak bark extract, related synthetic compositions, and method of using same |
| AU2002359529B2 (en) * | 2001-11-29 | 2008-02-21 | Greystone Medical Group, Inc. | Treatment of wounds and compositions employed |
-
2003
- 2003-12-23 CA CA002511440A patent/CA2511440A1/en not_active Abandoned
- 2003-12-23 JP JP2004563981A patent/JP2006511585A/en active Pending
- 2003-12-23 CN CNA2003801095668A patent/CN1744819A/en active Pending
- 2003-12-23 EP EP03808544A patent/EP1575359A4/en not_active Withdrawn
- 2003-12-23 WO PCT/US2003/041038 patent/WO2004057965A1/en not_active Ceased
- 2003-12-23 AU AU2003303335A patent/AU2003303335A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2511440A1 (en) | 2004-07-15 |
| EP1575359A4 (en) | 2009-08-05 |
| WO2004057965A1 (en) | 2004-07-15 |
| EP1575359A1 (en) | 2005-09-21 |
| JP2006511585A (en) | 2006-04-06 |
| AU2003303335A1 (en) | 2004-07-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1214081B1 (en) | Superoxidized water based on hypochlorous acid for the treatment of wounds | |
| US20040170703A1 (en) | Reduction of reactive oxygen species in chronic wound management | |
| CH701627B1 (en) | Process for the preparation of a composition of hypochlorous acid and its uses. | |
| RU2204394C2 (en) | Agent for treatment of fungal infection, gastric and duodenal ulcers induced by helicobacter pylori | |
| CN1074931C (en) | Antimicrobial agent for staphylococcus | |
| RU2412990C2 (en) | Arthrospira-based compositions and their application | |
| US20220202939A1 (en) | Preparation for improving activity and/or thermal stability of superoxide dismutase, and application thereof | |
| DE69127459T2 (en) | CELL PROFILERATION MATTRESS AND THEIR USE | |
| CN113440645A (en) | Composite lysozyme liquid dressing for wound surface and preparation method thereof | |
| CN1744819A (en) | Reduction of reactive oxygen species in chronic wound care | |
| US8568711B2 (en) | Antimicrobial compositions | |
| CN113069413A (en) | Hypochlorous acid gel supporting electron beam irradiation sterilization and preparation method thereof | |
| CN107903322B (en) | Method for preparing antibacterial collagen based on safrole epoxidation modification | |
| KR0164923B1 (en) | Antimicrobial agent based on chitosan | |
| KR102665695B1 (en) | Composition for wound healing or skin regenerating comprising methylsulfonylmethane and agent for wound healing or skin regenerating using the same and method for manufacturing the same | |
| CN115487182B (en) | Application of isothiazolinone as synergist of antibacterial drug | |
| CN119318335A (en) | Compound quaternary ammonium salt disinfectant for aseptic environment and preparation method thereof | |
| CN114431233A (en) | Composition for preparing disinfectant | |
| EP4072294A1 (en) | Antimicrobial composition | |
| CN113367168A (en) | Novel product applied to aquaculture animal disinfection and preparation method thereof | |
| CN101766190A (en) | Housefly larvae chitooligosaccharide preparation for preventing and controlling tobacco leaf diseases and application thereof | |
| SK277698B6 (en) | Topic gel mediator with immunomodulating properties | |
| JPS61152276A (en) | Sterilization of recombinant microorganism | |
| KR20040092677A (en) | Composition of treatment for athlete`s foot using mixture of alcohol and pyroligneous liquid or/and organic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |