EP1135116A1 - Use of poly (hexamethylene) biguanide for producing an agent for promoting the healing of uninfected wounds - Google Patents

Use of poly (hexamethylene) biguanide for producing an agent for promoting the healing of uninfected wounds

Info

Publication number
EP1135116A1
EP1135116A1 EP19990963370 EP99963370A EP1135116A1 EP 1135116 A1 EP1135116 A1 EP 1135116A1 EP 19990963370 EP19990963370 EP 19990963370 EP 99963370 A EP99963370 A EP 99963370A EP 1135116 A1 EP1135116 A1 EP 1135116A1
Authority
EP
European Patent Office
Prior art keywords
phmb
solution
hexamethylene
biguanide
poly
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.)
Ceased
Application number
EP19990963370
Other languages
German (de)
French (fr)
Inventor
Frank Jethon
Ulrich Kirschner
Katja SCHÖN-HÖLZ
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fresenius Kabi Deutschland GmbH
Original Assignee
Fresenius Kabi Deutschland GmbH
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to DE19856153 priority Critical
Priority to DE19856153 priority
Application filed by Fresenius Kabi Deutschland GmbH filed Critical Fresenius Kabi Deutschland GmbH
Priority to PCT/EP1999/009426 priority patent/WO2000033829A1/en
Publication of EP1135116A1 publication Critical patent/EP1135116A1/en
Application status is Ceased legal-status Critical

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/155Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)

Abstract

The invention relates to the use of poly (hexamethylene) biguanide as an agent for promoting the healing of or for treating wound healing impairments of uninfected wounds, or to the use of poly (hexamethylene) biguanide for producing such an agent. Poly (hexamethylene) biguanide with an average molecular weight distribution (Mw) of up to 15,000 is suitable. Poly (hexamethylene) biguanide with an average molecular weight distribution of 1,000 to 8,000, especially an average molecular weight distribution of 1,500 to 5,000 and most especially, of 2,000 to 4,000 is preferred. The poly (hexamethylene) biguanide can optionally be used with a surface tension-lowering tenside and/or optionally, in water, lactate-free Ringer's solution or sodium chloride solution, and is preferably used for soft-tissue wounds.

Description

USE OF POLY (hexamethylene) biguanide FOR PRODUCING A MEANS TO PROMOTE THE HEALING OF INFECTION FREE WOUNDS

technical field

The invention relates to the use of poly (hexamethylene) biguanide as an agent for promoting the healing or for the treatment of wound healing disorders in wounds that are free from infection, and the use of poly (hexamethylene) biguanide for the preparation of an agent for promoting the healing of wounds which are free of infection.

A particular problem in surgery in the treatment of wound healing disorders as such. As severe soft tissue defects, slow-healing wounds and occur in chronic wounds represent. Wound healing disorders caused by the size of a wound and local infections. The infection of a wound makes their antiseptic treatment necessary.

The concept of antisepsis was first in 1772 by Pringle (J. Pringle, observations on the diseases of the army, translated by AE Brande, lessons Generic bookstore, Altenburg, 1772) can prevent associated with means rotting coined. The development of locally applied antiseptic then went in the wake of Karbolverband, the use of zinc chloride solution over chlorine-containing solutions, sublimate (Robert Koch) and iodoform (Bill Roth) to azo dyes and sulfonamides. In the history of antiseptics any new development on the basic pursuit of optimal microbicidal action with optimum compatibility for the organism is based. The side effects of early antiseptics were severe in some cases, ranging from burns to general poisoning. With the discovery of penicillin and the local application of antibiotics, chemical antiseptics were pushed back initially. With the appearance of more and more antibiotic-resistant pathogens the picture changed again so that again today various local antiseptics come for wound treatment to apply and there is still a need for optimized in the safety and efficacy of drugs. Of poly (hexamethylene) biguanide (PHMB) is known from the prior art that there is a bactericidal and fungicidal activity has (see. For example, GB-PS 1,202,495). PHMB is therefore used in many fields as a disinfectant, for example in the form of solutions or sprays. they are used for example in the food industry for cleaning and disinfecting rooms and equipment, for the stabilization of beverages and for the cleaning and stabilization of water, for example, in swimming pools to combat algae and bacteria growth.

It is also known from DE-OS 35 37 627, that are obtained by combining PHMB with a molecular weight of 1700-2500 with a small amount of polyethylene glycol disinfectants, which are also used as a local antiseptics in the treatment of wounds. When PHMB is suitable according to this DE-OS, for example, the PHMB, which is marketed as the hydrochloride under the tradename Vantocil IB ® from ICI.

According to WO 94/27440 an anti-infective agent on the basis of PHMB is described having an average molecular weight of M w from 2900 to 15,000, which is present in the form of a Wundantiseptikums and / or a wound treatment agent. This PHMB can together with PEG at a ratio of PHMB to PEG of 6: 1 can be used: 1 to 24 hours. The agents are used as topical antiseptics, in many fields of medicine, which is called in soft tissue infections, as an example to the use.

In WO 97/00076 the use of PHMB salts (eg. As the hydrochloride salt) in the manufacture of medicaments for the topical treatment of microbial infections described (including the eye), and as antiseptics. They can be used for wounds and mucous membranes. The concentration of the PHMB is different for the various uses and is in therapeutic use as an antimicrobial agent is preferably at least 0.02% and especially at least 0.1%. In EP 0450117 a Ringer solution and its application is described as a bactericidal local wound treatment medicament, wherein the lactate-free Ringer solution contains additionally dissolved 0.1% to 0.2% of a concentrate biguanide consisting of a 20% aqueous solution of poly (hexamethylene) - hydrochloride solution consists, is dissolved in 100 ml per 1 g of polyethylene glycol having a molecular weight of about 4,000. The product sold under the tradename Vantocil IB ® ICI product is also described as being useful as PHMB. Under the trademark Lavasept ® an antiseptic for topical use is known, wherein the Lavasept concentrate is an aqueous solution of 20 wt .-% PHMB and 1 weight polyethylene glycol 4,000 and the PHMB is the commercial product Vantocil IB ® ICI.

In vitro studies Kalle Berger et al. (Kallenberger A., ​​Roth W. Ledermann A .: Experimental and bacteriological tests to select the detergent antibacterial Spüldrainage, (in G. Hierholzer and J. Rehn eds). The posttraumatic osteomyelitis, 5. 79, Schattauer, Stuttgart, New York, 1970) showed on the compatibility of rinsing solutions that have different physiological electrolyte solutions produce different effects. So Ringer's solution is well tolerated, while saline may already lead to significant cell damage. Among various chemical substances with good bacteriostatic or bactericidal action (chlorine-containing solutions, organic silver compounds, alcoholic mixtures with quaternary ammonium compounds) in particular, the iodophors in surgery have gained acceptance for the antiseptic treatment of wounds. Due to known side effects (Hernandez-Richter HJ, Struck, H.: Wound healing, Georg-Thieme-Verlag, Stuttgart, 1970) is the availability of iodophors limited.

As is known, currently used antiseptics have tissue-damaging effect (eg. Necrotizing example, the tissue formation inhibiting effect) and thus wound-healing inhibitory effect on, so that they are limited in application. Summary of the invention

The object of the present invention is to provide a means by which the wound healing in wounds that are free from infection, can be effectively promoted and can be effectively treated with the wound healing in wounds that are free from infection.

According to the invention it was surprisingly found that this object is achieved by the use of poly (hexamethylene) biguanide (PHMB, also referred to as polyhexanide) can be solved.

In the inventive use any antiseptic treatment of the wound surface and the wound edges to be carried out, but should rather be treated the wound itself in infection-free state or further treated.

In the known antiseptic wound treatment with PHMB only infections in wounds suppressed, with the result that the wounds of infections remain free and thus the wound healing process is not adversely affected.

According to the invention has surprisingly been found that PHMB has granulation-properties and thus itself acts wound-healing. The inventive use of PHMB earlier and improved granulation and epithelialization of the wound, thus improved blood flow to the wound surface and formation of new healthy tissue in conjunction with the Wundabheilungsprozeß is achieved, thereby improving the healing process and accelerated.

By "infection free" according to the invention wounds understood who are not infected, so no signs of infection (eg. as redness, odor, secretion, pus) and hence not or must not be treated antiseptic. The PHMB used in the invention suitably has a mean

Molecular weight distribution (M w) to 15,000 and preferably from 1,000 to 8,000. Preferred is a poly (hexamethylene) biguanide with a mean molecular weight distribution of from 1500 to 5000, particularly preferably a PHMB having a mean molecular weight distribution of 2000 to 4000 and in particular from 2,800 to 4,000, for example, having an average molecular weight M w of 2,600, 2,800, 3,500, 4,000 or 4,500.

The molecular weight determination is made viskosimetrischem way.

The preparation of the poly according to the invention (hexamethylene) biguanide is carried out in manner known per se, for example as described in DE-PS 16 20 938 or GB-PS 1,202,495, the disclosure of which is incorporated by reference herein in its entirety. can biguanide from the obtained poly (hexamethylene) optionally an undesired molecular weight fraction in a conventional manner, for example by dialysis, molecular filtration, HPLC, gel permeation chromatography (GPC), fractional precipitation, and the like, can be separated (see. for example, EP - PS 0,700,249). According to the invention also suitable commercially available PHMB, such as Vantocil IB ® or Arlagard ® E or other commercial products.

The PHMB used in the invention is in free form or in the form of a water-soluble salt, before, for example as the hydrochloride, as a powder (e.g., lyophilized) in 100% concentration or in aqueous solution. It is used in concentrations up to 40 wt, for example, 2 to 40 wt .-%, preferably 3 to 30 wt .-%, in particular 4 to 20 wt .-%, for example 4 wt .-%, 4.5 .-%, 5 wt .-%, 6 wt in aqueous solution (ie, as a concentrate) are available.

By "PHMB" both the poly (hexamethylene) biguanide and the poly (hexamethylene) biguanide in the form of a water-soluble salt it is meant herein.

The concentration in which the PHMB used in the invention or the aqueous solution of PHMB is used for the treatment of wound healing or for promoting wound healing depends on the intended use.

Suitable concentrations are generally in the range of 0.0001 to 0.1 wt .-%, preferably in the range of 0.0005 to 0.06 wt .-%, in particular in the range of 0.001 to 0.04 wt .-%, for example, 0.04 wt .-% (based on PHMB). According to the invention, the PHMB may be employed in the stated concentrations, for example in water, Ringer's solution, preferably lactate-free Ringer solution or common salt solution.

The PHMB used in the invention, together with the surface tension-reducing surfactants, such as used, for example, polyethylene glycol. Preferably, polyethylene glycol with a molecular weight of 1,500 to 6000 and in particular such a polyethylene glycol having a molecular weight of 4000, such as is sold under the trademark Lutrol ® E 4000 from BASF AG, applied. The ratio of PHMB to the surfactant is suitably in the range of 6: 1 to 24: 1, preferably in the range from 12: 1 to 22: 1 and in particular is 20: 1.

For example, according to the invention the commercial product Lavasept ® after appropriate dilution are employed to the use concentration.

According to the invention PHMB is applied in various ways, such as for example locally or systemically, orally, rectally, or vaginally in the eye. It takes place in animals and humans, preferably in humans, application.

Depending on the intended use can according to the invention, the PHMB in various Anwendungsfprmen or pharmaceutical preparation forms, such as in the form of aqueous solutions (optionally with a content of lactate-free Ringer solution or common salt solution, preferably lactate-free Ringer solution), emulsions, suspensions, gels, ointments or creams, tablets, capsules, dragees, suppositories and the like. In these preparation forms are also included for the preparation of the necessary for the formulation in the usual auxiliaries and additives. The saline solution can be used as 0.4 to 1.2 wt .-% solution. Preferably, however, physiological, that is, 0.9% saline, applied.

The application can be carried out according to the invention in the form of wound irrigation solutions, in the form of impregnated with the invention applied solution tampons (for example, in dental surgery), compresses or longuettes (for example, to cover postoperative left open wounds) and the like.

In therapeutic use intermittent application is preferred, with the wounds of one to three times daily, soaked or rinsed in accordance with the therapeutic requirements, with the inventively used PHMB. In addition, irrigation-suction drainage for irrigation can be applied internally according to the invention.

Because of the aforementioned surprising that promotes wound healing property PHMB can be used to promote wound healing in wound healing in many areas of medicine, such as in wounds of soft tissue or wounds on bones (skeleton) can be used. Preferably PHMB is sore use in soft tissue. So PHMB can for soft tissue wounds, such as in surgical wounds after appendectomy or Abdominaleingriffen or skin and Subcutis- and deeper soft tissue abscesses, after accidents in which, for example, the soft tissue of the upper and lower extremities, including hands and feet, as well as thorax, abdomen and / or back are affected are applied. may find use in the present invention, the PHMB especially in wound healing, such as occur in severe soft tissue defects in slow-healing wounds and chronic wounds. Thus, the use is useful in the aseptic bone surgery, for the treatment of wounds, which correspond to the types of wounds after 2-4 Hierholzer (The surgeon, 1991, Vol. 62, pages 861-865), of leg ulcers, bedsores, diabetic foot, of heavy and severely burned patients, in critically involved in accidents and patients with wounds in the area of ​​the nose and throat, such as the oral cavity, as well as for wounds around the eyes. According to PHMB can be used both in already infected wounds as well as fresh wounds (for example, type 2 wounds).

Explanation of the Figure 1

1 shows the course of the healing of fresh contaminated, non-infected (ie, infection-free) soft tissue wounds treated with either 0.04% sodium PHMB solution or Ringer's solution (see Example 4) is shown. From 1 shows a clear difference in the timing of wound healing between the two treatments is evident. Using the PHMB-containing solution significantly accelerated the healing process can be seen.

Ways of carrying out the invention

The examples below. serve to illustrate the invention.

example 1

Of poly (hexamethylene) biguanide hydrochloride having an average molecular weight M w of 2,600, polyethylene glycol 4,000 (Lutrol ® E 4000, BASF AG) and water A solution was prepared of the following composition by mixing them:

Poly (hexamethylene len) biguanide hydrochloride, M w 2,600% 6 wt .-

Polyethylene glycol, M w 4,000 0.3 wt .-%

Water 93.7 wt .-%

The prepared solution was successfully applied after appropriate dilution with water or lactate-free Ringer solution for promoting wound healing or for the treatment of wound healing disorders in soft tissue wounds. As poly (hexamethylene) biguanide hydrochloride, the commercially available product PHMB Vantocil IB ® or Arlagard ® was applied E ICI. Vantocil IB ® or Arlagard ® E is an aqueous solution containing as active ingredient 20% poly (hexamethylene) biguanide hydrochloride.

example 2

To produce another solution for use in the invention Example 1 was repeated except that the corresponding PHMB was used instead of PHMB hydrochloride.

example 3

Of PHMB with a mean molecular weight distribution (M w) of 2,800 and lactate-free Ringer solution, a PHMB-containing solution according to the invention to be used with a final concentration of 0.04 wt .-% PHMB was prepared by mixing these ingredients.

This solution has been used to promote wound healing in soft tissue wounds and bone wounds.

example 4

Testing the effectiveness of PHMB to promote wound healing:

As described below study to investigate the efficacy of PHMB-containing wound irrigation solution, the healing-promoting effect of PHMB used was investigated in soft tissue wounds. As wound irrigation solution, a 0.04 wt .-% PHMB-containing solution as obtained in Example 3 was used. As a reference solution Ringer solution was used. The study was designed as a randomized, double-blind, two-arm, multi-center, placebokontroUierte clinical phase III. 49 patients were treated with the rinse solution containing PHMB and 36 patients with the Ringer solution. In the patients it was adult patients who had impaired wound healing, whereby only patients were enrolled in the study, whose wounds the wound types 2, 3 and 4 corresponded to Hierholzer (The surgeon, 1991, Vol. 62, pages 861-865) , The types of wounds after Hierholzer are classified as follows:

wound type

1 "clinically clean" surgical wound (no significant tissue destruction or accidental contamination)

2 "clinically clean" contaminated wound (fresh, traumatic wound, fracture without significant bacteria sowing)

3 contaminated wound (open fracture II and III, the cavity opening with significant seed sowing)

4 heavily contaminated or infected wound (open fracture II and III over 2 hours after injury, faecal contamination).

The treatment of soft tissue wounds was performed as follows:

The wounds were treated openly moist (moist wound treatment). The flushing of open, infected soft tissue wounds was performed using a cannula of drain passages from or inserted Spüldrains. The antiseptic covering wounds was (x 10 cm 10 cm) were impregnated with PHMB-containing solution or with the placebo (Ringer solution) made with longuettes or compresses. The covering material was wetted twice daily.

The duration of treatment was 15 days maximum. The assessment of efficacy was based on a wound cores, which was composed of a wound base index and a wound margin index, wound base index and wound margin index were graded as follows:

Wound base index

10 necrotic

8 greasy

6 infected

4 granulating

2 almost cleared

0 healed

Wound margin index

10 kailös

8 flammable

6 indurated

4 indurated moderately hard

2 almost cleared

0 healed

Still further, the wound granulation, wound basic index, the efficacy and tolerability assessment and bacterial colonization of the wounds were observed using a microbiological accompanying studies were being conducted on treatment days 0, 2, 8 and 15 microbiological tests on germ type and number (semiquantitative). Here wounds were the "germs detectable" had microbiologically the result, but "infected" in the assessment of the wound as a "greasy" or who were "necrotic", classified as infected. Otherwise done an assessment on the basis of actually encountered germs. The safety assessment was based on the logging of adverse events and monitoring of laboratory parameters and subjective tolerability investigator assessment.

Randomization of patients was performed by computer using a specially created randomization. The statistical methods Repeated Measure- covariance, the life table analysis and methods of descriptive statistics were applied. (Description of the statistical methods used can be found in L. Sachs, Applied Statistics, 7th ed., Springer, Berlin Heidelberg New York, 1992, GAF Seber, Multivariate Observations, John Wiley & Sons, New York, 1984, JD veal, RL Prentice, The Statistical Analysis of Failure Time Data, John Wiley & Sons, New York, 1980, SAS Institute Inc., SAS / STAT ® User's Guide, version 6, 4th Ed., Volume 2, Cary, NC, SAS Institute Inc ., 1989.)

In this study, the following results were obtained:

In the study, a superior efficacy of PHMB-containing rinsing solution against Ringer solution showed. The Repeated Measure analysis of covariance with the initial wound area as Covariable showed a significant difference (p = 0.0003 per protocol, p = 0.0001 intent-to-treat) in the healing running between the two solutions used (see also FIG. 1).

Furthermore, the efficacy of the investigators for the PHMB-containing solution in 95.9% of cases with good or very good judged for Ringer's solution only in 62.8% of the cases.

Under treatment with PHMB-containing solution addition in infected wounds significantly faster (log-rank test, p = 0.0001) achieved sterility than using Ringer's solution. For compatibility in addition to the recording of adverse events, the measured laboratory parameters (white blood cell and red blood cell count, hemoglobin level, and hematocrit) and the subjective tolerance assessment were considered by the investigator. In no medication group adverse events occurred. The laboratory parameters showed a normal course. In all cases, treatment with PHMB-containing solution was evaluated as very good or well tolerated. The Ringer solution was evaluated in a case as moderately tolerated. Neither of the two solutions were certified as poor compatibility.

1 shows the course of the examined in the study wound healing in contaminated non-infected, fresh soft tissue wounds is shown both in treatment with the PHBM-containing solution and treated with Ringer solution, on the y axis of the wound core consisting of the assessment the course of healing of the wound and the wound edge at the indicated on the x-axis days according to the formula

rel. Score = Score Summer t "

starting Score

were evaluated. Lower values ​​mean there an improvement in the wound state. There was a significant difference in the time course of wound healing, also using statistical methods as described above (see FIG. Repeated Measure analysis of covariance and Lifetable- analysis), confirmed as significant. Using the 0.04 wt .-% PHMB-containing solution significantly accelerated healing process, recognizable by a previous granulation and epithelialization of the wounds was observed when treated with the Ringer's solution. In the figure 1, this is illustrated by the earlier and steeper slope of the curve during treatment with PHMB. Since they were fresh, not purulent wounds, this difference was not based clearly on the removing existing infections by the bactericidal PHMB. So that the wound healing is promoted by applying the 0.04 wt .-% PHMB-containing solution is confirmed. The surprising healing-promoting effect of PHMB-containing solution is thus both in already infected wounds as well as fresh Type 2 wounds which still manifests no infection had (see FIG. 1), pointed out.

The wound-healing effect of PHMB-containing solution thus depends not only on the microbicidal activity and compared with Ringer's solution equally good compatibility, but was caused by PHMB itself.

example 5

Example 3 was repeated with the exception that was used instead of there PHMB having a mean molecular weight distribution (M w) of 2,800 PHMB having a mean molecular weight distribution (M w) of 4,000.

The solution thus prepared with a final concentration of PHMB (M w 4,000) 0.04 wt .-% has been well as the solution of Example 3 successfully used to promote wound healing or for the treatment of wound healing disorders in soft tissue wounds.

The PHMB was applied in known manner e ICI separated by fractional filtration from the commercially available PHMB product Vantocil IB ® or Arlagard ® (see. EP 0700249 Bl).

example 6

Example 1 was repeated with the exception that was used instead of PHMB used there with an average molecular weight (M w) of 2,600, a PHMB with a mean molecular weight (M w) of 2,800. The solution thus prepared may, after suitable dilution with water, lactate

Ringer's solution, or saline as well as the solution of Example 3 successfully used for the treatment of wound healing disorders in soft tissue wounds.

example 7

Example 1 was repeated with the exception that a PHMB having a mean molecular weight distribution (M w) was used in place of 4,000 of the PHMB used there with an average molecular weight distribution (M w) of 2,600.

The solution thus prepared was used after appropriate dilution with water or Ringer lactate solution to the use concentration to successfully promote wound healing in soft tissue wounds.

The PHMB used was prepared in the manner described in Example 5.

example 8

(Mw) of 3,500, polyethylene glycol 4,000, and water was prepared by mixing the components, a solution of the following composition of PHMB with a mean molecular weight:

PHMB hydrochloride, M w 3,500 20 weight

Polyethylene glycol, M w 4,000 1 0% by weight

Water 79 wt .-%

The solution thus prepared can be used with water or Ringer lactate solution to the use concentration to successfully promote wound healing in soft tissue wounds or bone wounds after appropriate dilution.

The PHMB hydrochloride used was obtained in the manner described in Example 5. example 9

Another PHMB according to the invention to be used containing the same solution was made of PHMB with a mean molecular weight distribution (M w) of 3,500 and lactate-free Ringer solution by mixing to a final concentration of PHMB of 0.04 wt .-%. This solution has been used to promote wound healing in soft tissue wounds.

The PHMB used was obtained in the manner described in Example 5.

example 10

(W M) of PHMB with a mean molecular weight of 4,500, polyethylene glycol 4,000, and water was prepared by mixing the components, a solution of the following composition:

PHMB hydrochloride, M w 4,500 20 wt .-%

Polyethylene glycol, M w 4,000 1.0 wt .-%

Water 79 wt .-%

The solution thus prepared was used after appropriate dilution with water, lactate-free Ringer solution or common salt solution to the use concentration to successfully promote wound healing in soft tissue wounds.

The PHMB used was obtained in the manner described in Example 5.

example 11

Of PHMB with a mean molecular weight distribution (M w) of 4,500 and lactate-free Ringer solution, a solution according to the invention to be used with a final concentration of PHMB of 0.04 wt .-% was prepared by mixing these ingredients. The solution thus prepared can successfully promoting

Wound healing are used in soft tissue wounds.

The PHMB used was obtained in the manner described in Example 5.

example 12

Of PHMB with a mean molecular weight distribution (M w) of 4,000 and water A solution was prepared of the following composition by mixing them:

PHMB, M w 4,000 4 wt

Water 96 parts by weight

The solution thus prepared was used after appropriate dilution with water, lactate-free Ringer solution or common salt solution to the use concentration to successfully promote wound healing in soft tissue wounds.

The PHMB used was prepared in the manner described in Example 5.

example 13

Of PHMB with a mean molecular weight distribution (M w) of 3,500 and water A solution was prepared of the following composition by mixing them:

PHMB, M w 3,500 4.5 wt .-%

Water 95.5 wt .-%

To prepare a solution to be used according to the invention 0.2% of the above-prepared solution with 0.9 saline solution to a final concentration of PHMB of 0.02 wt .-% were diluted. The solution thus prepared was successfully used to promote wound healing in soft tissue wounds.

The PHMB used was prepared as described in Example 5. Fig.

example 14

(Mw) of 2,800, polyethylene glycol 4,000, and water was prepared by mixing the components, a solution of the following composition of PHMB with a mean molecular weight:

PHMB, M w 2,800 20 wt .-%

Polyethylene glycol, M w 4,000 1 0 wt .-%

Water 79 wt

Using 2.0 g of the solution thus prepared and the following ingredients according to the invention to be used a gel of the following composition was prepared:

PHMB-containing solution (M w 2,800) 2.0 g

Ringer solution (lactatfrei) 965.5 g

Hydroxyethyl cellulose (DAB) 32.5 g

The gel thus produced has been successfully applied for the treatment of wound healing disorders in soft tissue wounds.

example 15

For the preparation of a further according to the invention to use gel Example 14 was repeated with the exception that was used instead of PHMB used there with an average molecular weight of 2,800, a PHMB with a mean molecular weight (M w) of 3,500. The PHMB used was prepared as described in Example 5.

The gel thus produced has been successfully used to promote wound healing in soft tissue wounds.

example 16

For the preparation of a further according to the invention to be used in the gel (M w) of 4,000 and water by mixing the same was prepared a solution of the following composition of PHMB with a mean molecular weight:

PHMB, M w 4,000 20 wt .-%

Water 80 wt .-%

2.0 g of the PHMB-containing solution thus prepared were then used to produce a gel having the following composition:

PHMB-containing solution (M w 4,000) 2.0 g

Ringer solution (lactatfrei) 965.5 g

Hydroxyethyl cellulose (DAB) 32.5 g

The PHMB used was obtained as described in Example 5.

The gel thus produced has been successfully eingsetzt to promote wound healing in soft tissue wounds.

Claims

claims
1. Use of poly (hexamethylene) biguanide for the preparation of an agent for promoting the healing of wounds that are free from infection.
2. Use according to claim 1, characterized in that the poly (hexamethylene) biguanide has an average molecular weight distribution has to 15,000.
3. Use according to claim 2, characterized in that the poly (hexamethylene) biguanide has an average molecular weight distribution of 1,000 to 8,000 has.
4. Use according to claim 3, characterized in that the poly (hexamethylene) biguanide has an average molecular weight distribution 2000-4000 possesses.
5. Use according to one of the claims 1 to 4, characterized in that the poly (hexamethylene) biguanide with a surface tension depressant surfactant is used.
6. Use according to claim 5, characterized in that the surfactant is polyethylene glycol.
7. Use according to claim 6, characterized in that the ratio of poly (hexamethylene) biguanide to polyethylene glycol is in the range of 6: is 1: 1 to 24 hours.
8. Use according to claim 7, characterized in that the ratio is in the range from 12: 1 to 22: 1.
, Use according to one or more of claims 1 to 8, characterized in that the poly (hexamethylene) biguanide is used in a lactate-free Ringer solution or common salt solution.
10. Use according to one or more of claims 1 to 9, characterized in that. the poly (hexamethylene) biguanide in a concentration of 0.0001 to 0.1 wt .-% is applied.
11. Use according to claim 10, characterized in that the concentration of 0.0005 to 0.06 wt .-% by weight.
12. Use according to claim 11, characterized in that the concentration of 0.001 to 0.04 wt .-% by weight.
sore 13. Use according to one or more of claims 1 to 12 for the treatment of soft tissue.
EP19990963370 1998-12-05 1999-12-02 Use of poly (hexamethylene) biguanide for producing an agent for promoting the healing of uninfected wounds Ceased EP1135116A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
DE19856153 1998-12-05
DE19856153 1998-12-05
PCT/EP1999/009426 WO2000033829A1 (en) 1998-12-05 1999-12-02 Use of poly (hexamethylene) biguanide for producing an agent for promoting the healing of uninfected wounds

Publications (1)

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