JPS62161729A - Wound remedy containing monosaccharide - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention]

<Industrial Application Field> The present invention relates to methods and compositions effective in the treatment of wounds. More particularly, it relates to the use of monosaccharides, particularly fructose, useful in wound therapy. BACKGROUND OF THE INVENTION During severe injuries to the skin, for example due to severe burns, wounds, pressure ulcers, etc., the injured area is physiologically extremely unstable: following such injury or injury, the area in question normal physiological processes may be severely contaminated. Disruption of normal patterns of skin growth, blood flow, and immunity may occur to some extent due to injury to the area. Surgical treatment of such damaged tissues must therefore be able to control and substantially reverse these undesirable effects and, in one direction, facilitate the necessary treatment of the area. Because of the variety of different systems that can be adversely affected by such damage, it is difficult to find a single agent that is effective in controlling the sources of the various problems. For example, the most severe difficulty encountered is the immediate proliferation in the wound by a variety of different microbial barriers. What are the known agents of common invaders to wound sites, such as Staphylococcus aureus [! 1
taphylococcus reus], as well as various pathogens, such as Escheta coli, Pseudomonas aarugi
noaa], a variety of (yeast) fungi, especially Candida albicans.
] may also be found in the wound. Many antibacterial substances are known for their topical uses. Neither is effective without important drawbacks. For example, silver sulfadiazine, the currently selected antibacterial agent that is effective against Durum-positive and Durum-negative bacteria, has generated many resistant bacterial strains during its use, particularly in the Pseudomonas genus. Similarly commonly used petadine (Eatadtn)
e) (Povidone-Iodine) is effective against both Durham-positive and Durham-negative bacteria, but it causes severe pain to the patient when used, and it can cause white blood cells, polymorphonuclear cells, lymphocytes, and mononuclear cells in the wound. It will kill the bulbs and macrophages and sensitize the already severely injured area. Other known antimicrobial substances may be precluded from use by the low diffusion capacity of the composition or by the range of activity covering a relatively small number of bacterial species; is a factor to consider. There is a general reduction in circulation that is often observed in conjunction with compartmental entry into the wound site. For example, cessation of blood flow occurs gradually in sores or engorged ulcers, whereas rapid cessation occurs with thermal radiation and chemical burns. In either case, a reduction in blood flow rate means a corresponding reduction in the supply of nutrients and oxygen to the cells. Its deficiency therefore leads to the death of the tissue in the poorly supplied area, which is followed by the invasion of unfriendly bacteria and fungi. In order to proceed with treatment,
In addition to preventing the development of bacterial infection that lingers on the injured area, it is necessary to restore blood flow, which provides sufficient nutrients and oxygen to support regeneration of the wound area. Ideally, the formation of healthy granulation tissue should also be accompanied by increased blood flow. Granulation tissue is a highly vascularized tissue layer containing many fibrillar cells and collagen and interstitial material that supports recollagenation and reepithelialization during the normal wound healing process. To support. Another critical issue in the wound healing process is the initiation of wound closure. This generally proceeds in two stages and consists of contraction and epithelial migration. Contraction is a major skin transition process away from the wound green, while migration is the separation and migration of activated epithelial cells onto the wound surface. Since contraction itself leads to some degree of scarring, it is preferable that healing can be promoted by methods that increase the process of epithelial migration. The migratory process is characterized by accelerated mitosis of epithelial cells with movement across the wound site. The degree of epithelial migration and rate of wound closure can be accelerated and, in some cases, whether additional skin grafts are required to complete wound healing. It is clear that a number of different factors need to be controlled and/or promoted in order to achieve regeneration of damaged tissue. The processes involved and the mechanisms that should control them are so disparate that it is difficult to focus on a single treatment composition or treatment method that can simultaneously promote and promote most or all of the required processes. It turned out to be difficult. As discussed above regarding the variety of antimicrobial agents available, most available wound treatment compositions suffer from several drawbacks, are complicated to use, have inadequate infection control capabilities, or are expensive and inconvenient to the patient. It has disadvantages such as limited protection activity, limited range of protective activity, and high cost (for example, Wi
aa (ad,) BurnWosnd Covar
tnga*Vot, I Chap, 1. p, 11-22
. (see CBCP de saa, 1984). It has now surprisingly been found that certain single shield forces ζ, when used alone or in combination with known wound treatment compositions, provide additional protection against bacterial infection and inhibit granulation tissue growth. It was found to increase, promote revascularization of the wound site and/or arrest epithelial migration and wound closure. When single II is used in combination with known compositions, the effect on the wound healing process is marked and unexpectedly improved with respect to the above-mentioned characteristics. When used alone, monosaccharides exhibit remarkable and completely unexpected effects in controlling bacterial infections on damaged skin. Monofructose has proven to be the most effective and successful in this regard. -1l! A variety of monosaccharides are known to have been used for therapeutic purposes. For example, it is known to administer fructose intravenously to prevent red blood cell destruction during surgical extracorporeal circulation (US Pat. No. 4,448,771). It is known to use sorbose as a sugar substitute to prevent acid formation by bacteria in the mouth (U.S. Pat. No. 4,390,523), but it itself has no effect on bacterial growth. do not have. Oral administration of pure fructose to control stress responses in humans has also been discussed (US Pat. No. 4,024,250). It has been observed that irradiated glucose and fructose have a bacteriostatic effect.This effect is an obvious result of the peroxidized compounds produced by the irradiation. (Namike
at al. This point can indeed be contrasted by normal bacterial growth in the presence of glucose and fructose. Various natural substances such as honey or sand t11 (ie sucrose) are also traditionally used in folk medicine to prevent infections. Therefore, it is clear that monosaccharides have been used alone or in combination with other products for open wound treatment preparations, and that monosaccharides exhibit a more pronounced protective effect than two drugs such as sucrose and lactose. This has not been shown until now. As used herein, the term ``wound'' refers to skin or connective tissue injuries such as burns, pressure ulcers, ischemic trauma, chemical and radiation wounds, abscesses (αbce-aams), fistulas, bone defects, deformed healing of fractures, It is used for vasculitis, tropical parasitic ulcers, leprosy ulcers and sedentary or psoriatic lesions. Structure of the Invention The present invention provides at least one
The present invention relates to a composition characterized in that it contains an amount of 99 J of a pharmaceutically acceptable monosaccharide of the species and a pharmaceutically acceptable film-forming agent. In its preferred embodiments, the present invention relates to a composition containing an effective amount of fructose and a starch hydrolyzate, and preferably a starch hydrolyzate having fructose and dextrose equivalents of 13 to 17. These compositions are also suitable for use as carriers for wound treatment and therapy melons and other skin treatments used in the form of ointments. The present invention relates to the use of monosaccharides, particularly fructose, for the control of bacterial growth in wounds of mammals. (controlling rnicrobial
growth ) - refers to the ability of a monosaccharide to inhibit bacterial growth on uninfected wounds and to inhibit further growth or actually kill bacteria present in the wound in already infected i1J wounds. shall refer to. @bacterial (rnic)
``robial'' refers to bacterial or fungal infections. A particularly good effect is given by the addition of therapeutically effective amounts of monosaccharides to various film-forming agents that are routinely used as protective coatings for various types of wounds, especially burns. At the time of death, these drugs themselves form a simultaneous barrier to water and bacteria and are present here in different types of dry (non-gel) films, as well as in biological gels (gelatin and gelatin). /-! cutin substance), synthetic hydrogel,
Consists of ionic gel and adhesive. Monosaccharides can be used effectively in combination with any of the above substances. Extraordinarily favorable results are achieved when monosaccharides, particularly fructose, are combined with the film-forming starch hydrolyzate. Therapeutic uses of starch hydrolysates are described in U.S. Pat.
No. 12.252 and No. 4,414.202, the teachings of which are hereby incorporated by reference. - Speaking of itself, this substance is an extraordinarily effective treatment for burns, ulcers, lesions, etc. The starch hydrolyzate ultimately adheres to the underlying m-weave and forms a film that is semipermeable to gases and fluids. Thus, it provides a barrier that reduces plasma and fluid loss and also prevents the invasion of pathogenic bacteria. The effects observed when using starch hydrolyzate are far superior to the results seen when using traditional wound dressings. When used in combination with monosaccharides, the wound healing effect is improved tremendously, producing results hitherto unobtainable when using starch hydrolysates alone. For example, the use of a mixture of starch hydrolyzate and monosaccharides, especially glucose or fructose, has a significant effect on the wound revascularization process. Within 15 minutes to 6 hours after such use, the treated wound will develop an intense bright red color, vascularization will occur in the area, and visible evidence of the site's return to normal circulation. It is part of the normal healing process that revascularization does occur, and the rate of restoration of new blood vessels to injured tissue is greater than that seen with starch hydrolyzate alone. It is unexpectedly faster when treated with starch and fructose, which has a synergistic effect when combined with starch hydrolyzate, and the end result is much faster than when either of the two substances are used alone. Sometimes it is unattainable. A similar surprising effect is seen with the growth of granulation tissue. As noted above, the visible appearance of healthy granulation tissue is the starting point of the healing process, and the many lines associated with the gradual development of granulation. Healing is largely dependent on the reorganization of the connective tissue in the area damaged by the microblasts.The use of starch hydrolyzate alone has an effective effect to some extent on promoting the formation of granulation tissue: such m-cells When using starch hydrolyzate alone,
Relatively smooth outer arm. On the other hand, when starch hydrolysates are used in combination with monosaccharides, the granulation tissue takes on a very different appearance, being more granular, with rough surfaces, and greater activity in the tissue resulting in a faster healing rate. It shows the level. Particularly remarkable, however, is the effect that the added monosaccharides have on the wound closure process. This process is critical to the progression of healing because if it is fully developed, the need for skin grafting can be reduced or avoided altogether. One of the major problems with many of the known film-forming agents is that they are rarely able to promote wound closure, so skin grafting is always necessary for wounds of substantial size. Only starch hydrolysates have been shown to have a dramatic effect on this process, and actually significantly reduce the need for skin grafts. However, when combined with monosaccharides, the observations regarding wound closure are truly exceptional, with larger wounds showing complete closure in an even relatively shorter time than was previously possible. The effects of added monosaccharides are themselves particularly pronounced in promoting epithelial mitosis and migration; this can be demonstrated both macroscopically and microscopically. Therefore, the use of compositions containing both starch hydrolyzate and simple sugars, especially fructose, reduces or eliminates the need for skin grafts to a far greater extent than is possible with any known wound dressing. I can do it. Finally, of course, the added monosaccharides have an antimicrobial effect in combination with the starch hydrolyzate. Starch hydrolyzate alone is M
It is known that IJ has a remarkable ability to control the level of bacterial infection in wounds, and when combined with monosaccharides this ability is greatly enhanced, resulting in virtually no increase in the number of children at the site of application. completely prevent it. With all of the superior effects observed with film-forming agent-monosaccharide combinations, the compositions of the present invention provide an excellent method for treating damaged or scarred tissue. Monosaccharides alone are particularly effective as antimicrobial agents. It has been shown to be highly effective in controlling bacterial infections at wound sites, particularly in preventing the development of infections. These results demonstrate that clinically FL bacteria and M.
This was also observed in vitro under controlled conditions (see Example 3); these compounds inhibited colonization of both Durum-positive and Gram-resistant bacteria. It is particularly preferred because of its effectiveness in i15 control of growth and possibly opportunistic fungal infections. Monosaccharides are microbiostic (mtcrobiotic)
), but also to some extent microbicidal (m1
crobtcida L). For example, exposure of bacteria commonly found in wounds to a dose of fructose has been shown to cause visible disintegration of large numbers of bacterial cells. As mentioned above, it can be used in wounds where infection is already present as well as in injured areas of the skin where infection has developed to some extent. The antibacterial action of monosaccharides has been demonstrated by the addition of traditional treatment methods, such as bandages,
It is particularly effective when used as a pre-treatment of a wound prior to the use of gels, films, etc., or as a post-treatment treatment when other methods have not produced the desired results. This treatment can be accomplished in a variety of ways. For example, as a pretreatment for burn patients, areas of damaged tissue are placed in a bath consisting of a monosaccharide-containing V solution.
Soaking can be for a sufficient period of time to inhibit undeveloped bacterial growth. The bath solution may have a concentration of about 20 to about 95%, but preferably the concentration ranges from about 20-60%. The soaking treatment time varies depending on the severity of the wound. For small, fairly W6 partial wounds, the time to apply force depending on the monosaccharide concentration of the solution may be 24 hours or less. Those skilled in the art will know that the more monosaccharides in the solution, the more they tend to exert a proportionately greater osmotic effect on the wound, thus drawing fluid. For smaller wounds this is not a major problem; this effect occurs, for example, in the treatment required for patients with extensive burns. If it takes, simple sugars! It is desirable to limit the If or keep the treatment time short, e.g. for very large wounds as an 8-immersion medium (
When using corn syrup with a high fructose concentration (assuming such is conveniently available), the steeping time can be as low as S! Extremely high concentration, approximately 95%
It should not take more than about 1 or 2 hours to complete. On the other hand, diluting the syrup by about 4 times increases the soaking time proportionally. Similarly, as a pre-treatment for less extensive wounds, the injured area may be as painful with monosaccharide solution as with typical saline solution, which may cause damage to the injury. Summer - It can also occur due to V-drip. Again, the wound treatment time will vary depending on the size of the wound and the concentration of monosaccharide. The maximum recommended time for large wounds is 1-2 hours at a time. For smaller wounds, within 24 hours,
Up to 6 hours, several times a day is acceptable. Monosaccharides can also be used directly on burns or wounds in dry powder form. The powder is simply sprinkled onto the wound and left on for a period of time depending on the thickness of the wound. For example, for small wounds, the powder may be left in the casing for up to 24 hours, during which time the stool may be repeated 4-6 times. For extensive wounds, use should generally not be longer than 1-2 hours. In the practice of the present invention using only monosaccharides, the bath should have a monosaccharide concentration of about 20 to 195% weight/volume, with a preferred concentration of about 20 to about 60%. be. For solution preparation, the dry form of single s whole ius can be mixed with a pharmaceutically acceptable liquid vehicle suitable for localized treatment. Preferred diluents are distilled water, balanced salt solution, common salt or Ringer's solution. These and other pharmaceutically acceptable solutions are well known to those skilled in the art; particularly preferred are balanced salt solutions which themselves are known to have beneficial effects on wound healing processes (U.S. Pat. No. 4,414,202). solution p
H is maintained at about 5 to 7.4, preferably about 6-7. Alternatively, the use solution is diluted or undiluted, highly concentrated fructose corn syrup, which is currently available. When used in dry form, monosaccharides can be chemically pure powders. Particularly useful are dry high fructose corn syrup powders such as Arnerican Maize Coynpan.
3/ Made by (Indiana). This product is a mixture of approximately 95% glucose and fructose.
Umbrella is a high molecular weight sugar. The film-forming composition of the present invention contains an effective amount of at least one pharmaceutically acceptable monosaccharide having about 3 to 7 carbon atoms and a pharmaceutically acceptable film-forming agent. In preferred embodiments, the pharmaceutically acceptable monosaccharides of the present invention are pharmaceutically acceptable aldose ring or pharmaceutically acceptable ketose sugars. Among the pharmaceutically acceptable aldose rings to which the present invention is directed are erythrose, threose, ribose, Arapino-xylose, lyxose, allose,
These include alginate, glucose, mannogulose, idose, galactose and talose. Among the pharmaceutically acceptable ketose sugars preferred for use in the compositions of the invention are erythrulose, lipulose xylulose, busicose, fructose, tagatose, and sedoheptulose. Preference is given to ζCD) sugars, in which both the CD) and CL) isomers can be used. All of the above aldose and ketose sugars can be used as the monosaccharide component of the compositions of the present invention.Among the glucose and ketose sugars of the aldose ring, fructose and nrubose are particularly preferred. Among these, ketose sugars are most particularly preferred, among which fructose is the most preferred monosaccharide for use in the compositions of the invention, since the proportion necessary to achieve the desired effect is It is possible to use less time at 9 o'clock. The monosaccharide preferably accounts for about 5% of the weight of the composition.
present in an amount of from about 30% to about 30%. The monosaccharide component may be a mixture of two or more types of monosaccharides. For example, high fructose corn syrup, available in powder form, generally contains about 95% glucose and fructose gold in total, with both shields being approximately equal in amount. Such powder is called starch hydrolyzate. Preferably, the amount is 30% or less, and a mixture may be used instead of adding a single monosaccharide. In another preferred embodiment of the invention, 1L pharmaceutically acceptable film forming agents include, but are not limited to, starch hydrolyzate, polyvinyl vicritone, polyvinyl alcohol, ethylene glycol, albumin, cellulose, gelatin. , solubilized keratin, and dorocolloids, such as alginate, gum karaya, gum arabic, gum tragacanth, agar, and porgy bean gum. Among these film-forming agents, starch hydrolyzate has the highest H4
Yes. Those skilled in the art will appreciate that starch hydrolyzate is a common name for a mixture of carbohydrates most commonly classified by their dextrose content. The starch 7111 moisture waste of the present invention has a dextrose equivalent (tt) of 85 or less, preferably 4o or less. More preferably, the dextrose equivalent of the starch hydrolyzate of the present invention is about 5 and 4.
Chill between 0. Even more preferably the dextrose equivalent weight of the starch hydrolyzate is between about 7.5 and 30. Even more preferably the starch hydrolyzate is about 10 to 20
with a dextrose equivalent in the range of . Most preferably, the starch hydrolyzate of the present invention has a dextrose equivalent weight in the range of about 13-17. Those skilled in the art will know that starch hydrolysates having dextrose equivalents in this most preferred range are more particularly malt dextrose. "Pharmaceutically acceptable" is understood to mean pure and sterile. Although known methods including dry heating, filtration or irradiation can be used for sterilization, irradiation is not particularly recommended for monosaccharides as it can affect the molecular structure. The action of the film-forming agent in combination with monosaccharides can be further improved by the inclusion of small amounts of optional ingredients. Optional ingredients generally do not account for more than 5% of the total weight of the composition. In another preferred embodiment, the primary additional ingredient to the composition of the invention is one that comprises ascorbic acid or a pharmaceutically acceptable salt thereof. Those skilled in the art know that ascorbic acid or a pharmaceutically acceptable salt thereof promotes the formation and growth of healthy granulation tissue. Among the pharmaceutically acceptable ascorbate salts contemplated for use in the present invention are sodium ascorbate, potassium ascorbate, and calcium ascorbate. However, I would like to emphasize that the acid, ascorbic acid itself, is the most preferred. If used, the ascorbic acid component is used at about 0.1-5% of the total weight of the composition, most preferably about 1-3.5% of the composition. In another preferred embodiment, the composition of the invention comprises one or more pharmaceutically acceptable species selected from the group consisting of iron, calcium, copper, magnesium, selenium, silver, manganese, zinc and mixtures thereof. Contains metal salts. The inclusion of one or more of these salts in the compositions of the present invention is beneficial in their therapeutic process. Among the preferred salts, salts containing ferrous iron (monovalent ion) f: are most preferred. For example, ferrous sulfate,
The use of one of ferrous chloride or ferrous gluconate is preferred. Among these, use of ferrous sulfate is particularly preferred. It is emphasized that more than one of these salts can be included in the compositions of the invention, so that the ferrous salt is one of the metal salts of the above-mentioned type. Can be used with the above. Of course, ferrous sulfate is particularly preferred. Other salts of interest for use here include:
Calcium ascorbate, calcium chloride, calcium iodine, calcium permanganate, calcium phosphate (1,2 and 3), calcium gluconate, zinc acetate, zinc carbonate, zinc chloride, zinc citrate, iodine Zinc acid, zinc oxide, zinc permanganate, zinc peroxide, zinc salicylate, zinc stearate, zinc sulfate, magnesium chloride,
Magnesium citrate, magnesium chloride, sulfurized magnesium, manganese chloride and sulfuric acid steel. Preferred silver salts are silver mononitrate, silver citrate, silver iodide and silver lactate. Iodine in elemental form and iodine complexed with starch hydrolyzate by heating and tinctures of iodine, iodide salts such as Lugol's solution can also be added. Particularly preferred are sodium and potassium iodide, sodium and potassium iodate, calcium iodate and calcium iodide. Aqueous solutions of dilute pvp-iodine, normal saline or balanced salt solutions can also be used effectively in conjunction with the treatments of the present invention. Further additional components may be one or more adenosine phosphates, ie ATP, ADP or AMP. In yet another preferred embodiment of the composition of the invention, the composition contains a compound selected from the group consisting of alpha-ketoglutaric acid and pharmaceutically acceptable salts of alpha-ketoglutaric acid. Alpha-ketoglutaric acid and its salts promote collagen formation and thus increase the rate of wound healing using the compositions of the present invention. The kernel component is generally present in amounts of 1-2% or less. Finally, there are further ingredients that can be included in the compositions of the invention. This component is one or more amino acids that enhance the treatment. In preferred embodiments, one or more
All of the following amino acids can be provided in the composition of the invention: isoleucine, leucine, lysine, methionine, phenylalanine, threonine/, driftfan, valine, tyrosine, alanine, arginine,
Glycine, proline, histidine, serine, asparagine, aspartic acid, cysteine, cystine, glutamine and glutamine relatives, among which glycine, proline and lysine are particularly preferred. It is to be understood that as used herein the term "amino acid 0" is intended to refer to both the pure form and the hydrochloride salt of the amino acid.Thus, in a preferred embodiment of the invention in which all of the amino acids are used, the preferred 38! In a particularly preferred embodiment, the compositions of the invention include starch hydrolyzate and More particularly, the composition of the invention comprises a monosaccharide selected from the group consisting of d-fructose, d-glucose Md-sorbose.
Contains starch hydrolyzate and d-fructose. Preferably fructose accounts for up to about 30% of the total weight of the composition. In another preferred embodiment, the composition containing d-fructose and starch hydrolyzate having a dextrose equivalent of 40 or less is supplemented with one or more of the following additives: preferably of the amino acids mentioned above. 181 or two or more amino acids: alpha-ketoglutaric acid or a pharmaceutically acceptable salt thereof: ferrous salt, preferably ferrous sulfate; from the group consisting of calcium, zinc, manganese, magnesium, copper, selenium and silver Another pharmaceutically acceptable salt of the selected metal. In particularly preferred embodiments of the invention, all of the above-mentioned components are included in the composition. Therefore, in a particularly preferred embodiment of the invention, the primary i of starch hydrolyzate having a dextrose equivalent of 13 to 17 is present in a concentration of 5-30%.
- fructose; 1-5% IM ascorbine [;0
．． Ferrous sulfate at a concentration of 1-1%; zinc salt at a concentration of less than 1%; alpha-ketoglutaric acid at a concentration of about 1-2%; and 0.1
At least 1' present at -1% precision! Compositions are provided that include amino acids of II (% concentrations are based on the total weight of the 'l#1 composition). For wounds that are infected only to the extent of the wound or are uninfected, it is necessary to control the infection to a measurable level by mixing monosaccharides. However, especially in the case of severe infections, it may be desirable to also include a small amount of one of the classes of antibiotics or antifungals commonly used in the treatment of wounds. Among the useful antibiotics are streptomycin, inicillin, tetracycline, silver sulfadiazine, sul7anilamide, methylated sulfanilamide (5xlfartylonR), -k77rosboria and CF7mi/-/lycoside. Useful antifungal agents include nystatin (mycostatsn), or gramicidin. It should be noted that only small amounts of antibiotics need to be added. The compositions of the invention can be used effectively in regular programs of wound treatment. For example, in a preferred wound treatment method, a starch hydrolyzate monosaccharide powder formulation is applied directly to the wound 4 and 12 times per day. Typically, the wound is first surgically incised and then
Remove all dead tissue. Dissection can also be facilitated using water pulsing devices; enzymatic dissection is also effective, with proteolytic enzymes such as rravasmR%s
ioBmm, =y-lagenase, etc. are used. According to the teachings of US Pat. No. 4,414,202, prior to use of the film-forming composition, the wound is preferably irrigated with a buffer solution containing 6-7.8 pg. It has been found that irrigating and/or soaking the wound with a dilute (0.05-1%) pvp-iodine solution for 5 to 30 minutes before applying the composition accelerates the wound healing action of the dessicant. Just in case. The wound is then coated with the starch hydrolyzate/monosaccharide composition using enough of it to form a film over the wound. The wound may then optionally be covered with a preferably non-adhesive dressing that can be removed daily to repeat the procedure. This method of treatment is particularly effective for mammalian skin wounds and is most suitable for treating human wounds. Small amounts of pharmaceutically acceptable zinc, calcium, ferrous, copper, manganese, magnesium salts and silver when monosaccharides are used as active ingredients in the pretreatment solution.

It is often desirable to contain [salt]. These optional components are generally used in amounts of only about 0.001% to about 5%, preferably about 0.01% to about 0.1% of the total solution. These salts are known to have beneficial effects in the wound healing process. The salts to be used here include calcium ascorbate, calcium chloride, calcium iodate, calcium permanganate, calcium (1, 2, and 3 hydrogen) phosphate, calcium gluconate, zinc acetate, zinc carbonate, zinc chloride, citric acid. Zinc acid, zinc iodate, zinc oxide, permanganese [zinc,
Zinc peroxide, zinc salicylate, zinc stearate, zinc sulfate, magnesium chloride, magnesium citrate, silver nitrate, silver iodide, silver lactate, magnesium chloride, magnesium sulfate, manganese chloride, steel sulfate, ferrous sulfate, ferrous chloride iron, and ferrous gluconate. Also useful are iodine salts such as potassium iodide or iodate, sodium or calcium, and elemental iodine or PVP-iodine. Although they can be used alone or in combination with solutions or dry powders, it is generally preferred that the total of these additional ingredients does not exceed 5% in total. Other possible additives are very small amounts of antibiotics such as sulfonylamides (S1L
lfa-mylonR) sulfadiazine, silver-sulfadiazine, zinc-sulfadiazine, nitridines, tetracyclines, cephalosporins, aminoglucosides, clindamJcin and antifungal agents such as rrLycostatsn. Nystatin or Gramicidin. It is well recognized by those skilled in the art that for use in the prevention of bacterial infections, the components of either solutions or dry powders must be sterilized prior to use. Although there are no particular restrictions on the sterilization method, irradiation is not a recommended method because irradiation can affect the molecular structure of ηl sugars, especially in solution. Dry heat sterilization is particularly suitable for the purposes of this invention. The bacterial growth control method of the present invention is suitable for use on mammalian skin wounds. However, the method of the invention is particularly well suited for the treatment of human skin. The method of the invention may be better understood with reference to the following non-limiting example. Example 1 The following is an example of the wound treatment composition of the present invention. In both cases, fructose is produced by PfanstiehL Lab.
oratories. M-150 is a chemically pure fructose produced by M-13-17, Inc., Waukttgan, Ill.
The dextrose [! Starch hydrolyzate (Ma
ttrsn, GrainProcessing
Corporation, Mwscatine, Ia.
, )'1 It was the one to point to. Starch hydrolyzate must be sterilized by irradiation prior to use. 1. Af-15095# Fructose
5yn, M-tso
71'fructose
30y stone, M-15088fl fructose 10
g ascorbic acid 2
g ■, M-15072fl fructose 15
f Sodium ascorbate 3
yV, M-15081jl Fructose 15
:J ascorbic acid
3! jV1. Af-15077g Fructose 2J
/Potassium ascorbate 2
g Dalicin 0.33
ylysine 0.33
g Proline 0
．． 34g ■, M-15080g fructose 1
8,9α-ketoglutarate
1y ferrous sulfate 0.
1p amino acid (equal composition of 20 amino acids) 0.9
Example 2 A. An 84-year-old Caucasian woman had progressive encephalopathy, Alzheimer's disease, malnutrition, cachexia, and an untreated sore ulcer in the left ischial region. The size of the ulcer at the start of administration was 5.5x6x1.8an.
Met. There was a large amount of dead tissue emitting a foul odor. To culture the wound, first completely dissect the diseased tissue and then TIE-σ-8QL. Thoroughly washed with balanced salt solution. M-1 in the ulcerated area
D-Gelcol M (starch hydrolyzate) of 1113-17 per 50° dextrose was packed. The subsequent treatment is 1
It was to wash twice a day with salt solution and use starch hydrolyzate. After three weeks of treatment, in which the ulcer was each covered with a non-adhesive bandage, the infection decreased and the size of the ulcer decreased, but healing proceeded only very slowly. Treatment continued in the same manner at the temple points, but instead of starch hydrolyzate alone, a mixture of starch hydrolyzate and fructose in a ratio of 80:20 was used. An immediate clinical response was demonstrated by the formation of more highly vascularized granulation tissue, faster filling of the crater, faster reduction of ulcer surface area, and faster epithelial growth. Additionally, the exudate normally present in ulcers was significantly reduced, and a stronger, better organized, and more sticky film was observed on the granulation structure. Multiple layers of this film were seen to adhere and connect several areas of the granulation tissue platform of the ulcer. After 3 weeks (original 6 weeks), the ischial ulcer was completely healed. B. A 67-year-old woman has suffered from cirrhosis for 12 years, is completely paralyzed, and has severe, severely infected 4th degree compression in both sacrum and ischial areas. An rljI tumor had developed. A wound treatment agent was to be administered to this woman, and the following treatment was carried out for 1 ft. Twice daily equilibration, buffered salt bath washing, and application of M-150 starch strength n-hydrolysate powder, healing and infection control were initiated from the first day of treatment. After 3 weeks, the ulcerated area had healed to about 20% of its original size. At this point, the lesion on the right side was treated with starch hydrolyzate (73 parts).
, fructose (24 parts), ascorbic acid (2 parts),
Treatment was started with an isotropic compound (1 part) of 20f3Il amino acids. The lesion on the left side was subjected to the previous treatment rfIt and served as a control. After 8 weeks, 90 ulcers were treated with the combination regimen.
% cured, -10,000 controls were only 35% cured. Example 3 The following example demonstrates one of the antibacterial effects of monosaccharide sugars in vitro. Tissue samples of infected lesions were removed from the center of each wound with a skin punch, and a 2% sample had an average IT of approximately 0.7 g. M
Textile sample f: The two tissues were immersed in 95% ethanol and dried by fire to remove the surface contamination.
．． Grind it with OM salt solution until it is finely ground. Serial 10-fold dilutions were made in saline and samples were plated using the fluidized plate method. Quantification was performed on random anaerobic bacteria for 24 hours and on plates incubated under anaerobic conditions for 48 hours and recorded as microorganisms per gram of tissue. Following identification and quantification, all microorganisms were transferred to ETHA slats (E:THA is enriched Todd-H
awitt Bouillot 7 (ETHB) Todd-Hewitt
t Broth (Balti Nore Biolog
ical Laboratories), 0.5% Yeast Extract (EBL), 0605% Hemi 7 (Ea
stman Kodak Co.) and 0.005% menadione (SiμC chemical Co.) t-containing,
(prepared by adding 1.5% agar (DIFCOLabs)). All microorganisms were allowed to grow for 24 hours before culturing in sugar wells. The following sugars were used in the bacteriostatic comparative test: nigerose, fructose (monosaccharide), and sucrose, lactose (disaccharide). Each sugar solution was in a 10ν tube of ETHB with rlo, 20,3
0°50 or 70% CW/V) and then autoclaved. The pH was adjusted to approximately 7.4. About I
A solution of 0.0, Iau with 10" microorganisms was then added to 6 tubes to give a final concentration of 10" microorganisms/d.
ivtts) and cultured anaerobically in Gas Pak jars (EEL) for unconditional anaerobic emptying. At predetermined intervals, remove the tube from the culture and place it in the column.
The optical density 'fI: was measured at n Hita:hi 124. The results of the two runs are shown in Tables 1 and 2. Our results show that monosaccharides, rather than disaccharides, exhibit particularly unexpected growth-inhibiting effects, requiring much lower sugar concentrations to achieve gating. Table 1 Incubation 1) Sugar concentration required to reduce bacterial growth by 50% after 24 hours 2) αt tal) Values obtained for at least two of each microorganism clinically isolated. This is the average value of the results obtained. 2) Bacteria are cultured under appropriate conditions as described in Materials and Methods 3)
Table 2 Culture 1) Sugar concentration required to reduce bacterial growth by 90% after 24 hours 2) Staphylococt, US 20 74
．． 3 19.6 47a'ttrgwa 1) Same example meeting as in Table 1. This example demonstrates the effective treatment of wounds using a monosaccharide-containing M treatment solution: A. The subject suffered from progressive organic encephalopathy, paralysis, spasticity of the upper and lower limbs and a large area of the right thigh measuring 12 cm X 8 X 2 α. This case occurred in a 90-year-old woman suffering from deep pressure ulcers (bedsores). The pressure ulcer was filled with a large amount of dead tissue and a large amount of purulent, foul-smelling exudate. X-rays of the hip showed a metal hip replacement prosthesis and osteomyelitis in the femur. Pressure ulcers were washed twice a day with balanced salt solution and sprinkled with starch hydrolyzate powder having a dextrose equivalent (D, E,) of 17. If necessary, dead tissue was removed from the ulcer. Starch hydrolyzate alone reduced the accompanying malodor, but purulent exudate continued and the patient suffered from 102-103
I have a fever at 7. The femoral (Asαd) osteomyelitis was surgically removed and the remaining hole was thoroughly irrigated with balanced salt solution. The femoral and acetabular areas were scraped with a curette. The remaining wound was then treated twice daily. , washed with balanced salt solution and chemically pure fructose powder (Pfansttghl
Laborα-torigs, MrLscatitse
, 1. A) was sprayed. Most of the remaining infections were gone. The odor characteristic of this infection subsided within 24-48 hours and healthy, highly vascularized granulation tissue began to fill the cavity. The epithelium also began to grow centripetally. Four weeks after surgery, the original ulcer site was 80% healed and the patient was released from a lengthy emergency room stay. B, A 72-year-old woman with a subhard hematoma in the occipital region, underwent craniotomy to remove the hard subplate Il! I was removed. During the recovery period, the patient continued to lie upward for several days without any pain, and developed a sacral pressure ulcer with severe itching, severe infection, and a foul odor that extended to the sacrum. At first povidone-iodine soaked syllables resulted only in worsening and enlargement of the ulcer. At this point, high fructose corn syrup powder CDE4
2-55) 'Healing using iH was started. The powder was sprinkled on the wound twice a day and then washed with a balanced salt bath. Control of the infection occurred almost immediately at day 21 of treatment; this was also achieved with the formation of highly vascularized, rapidly growing granulation tissue. After starting treatment in this manner, follow-up treatment was started approximately 2 weeks after starting treatment at HFG5 1fi'. ll
Fc! Starch hydrolyzate (DE-
13-17) and HFC8 powder (70:30) was used. Healing progressed rapidly with complete closure of the original ulcer not achieved after 8 weeks. Applicant Ann No. 21 N Silverati Senior Agent Patent Attorney Takehiko Saito. ) 1-+ , -Re Procedural Amendment November 21, 1985 Commissioner of the Patent Office Kuro 1) Akio Yu 1. Indication of the case 1985 Patent Application No. 249777 2. Name of the invention Wound containing monosaccharides Therapeutic agent 3. Relationship with the person making the amendment Patent applicant name: Anthony N. Silverati Sr. (1 other person) 4. Handwritten specification attached to the representative application

Claims (1)

1. A composition comprising at least one pharmaceutically acceptable monosaccharide having about 3 to 7 carbon atoms and a pharmaceutically acceptable film-forming agent. 2. The pharmaceutically acceptable film forming agent is a starch hydrolyzate having a dextrose equivalent of 85 or less, polyvinylpyrrolidone, polyvinyl alcohol, ethylene glycol, albumin, cellulose, gelatin, solubilized keratin, alginate, gum karaya, gum arabic, selected from the group consisting of gum tragacanth, agar and chinensis, and wherein the monosaccharide is selected from the group consisting of pharmaceutically acceptable ketose sugars and pharmaceutically acceptable aldose sugars. A composition according to scope 1. 3. Claim 1, wherein the film-forming agent is a starch hydrolyzate having a dextrose equivalent of about 5 to 40.
The composition according to item 1 or 2. 4. The dextrose equivalent of the starch hydrolyzate is about 1
A composition according to any one of claims 1 to 3 in the range of 0 to 20, preferably about 13 to 17. 5. Monosaccharides from about 0.01 to about 50 wt% of the weight of the composition
5. A composition according to any one of claims 1 to 4, preferably present in an amount of about 5 to about 30 wt%. 6. The pharmaceutically acceptable sugar is erythrose, threose, ribose, arabinose, xylose, lyxose,
Claims 1 to 5 are selected from the group consisting of allose, altrose, glucose, mannose, gulose, idose, galactose, talose, erythrulose, ribulose, xylulose, busicose, fructose, sorbose, tagatose, and sedoheptulose. The composition according to any one of clauses 5 to 6. 7. The composition according to any one of claims 1 to 6, wherein the sugar is a D-isomer. 8. The composition according to any one of claims 1 to 7, wherein the sugar is fructose, glucose, or sorbose. 9. The composition according to any one of claims 1 to 8, wherein the sugar is fructose. 10. Ascorbic acid and pharmaceutically acceptable salts thereof, α
- Any one of claims 1 to 9 containing one or more additional compounds selected from the group consisting of ketoglutaric acid and its pharmaceutically acceptable salts, amino acids, and iodine compounds. Composition according to item 1. 11. The composition according to any one of claims 1 to 9, which contains a ferrous salt. 12. 5 to 30 by weight based on the total weight of the composition
% concentration of fructose, 1-5% concentration of ascorbic acid, 0.01-1% concentration of ferrous sulfate, 0.01
12. A composition according to claim 10 or 11 containing -0.1% zinc salt. 13. A wound treatment agent containing a pharmaceutically acceptable monosaccharide having 3 to 7 carbon atoms as an active ingredient. 14. Claim 13 in which the monosaccharide is fructose
Therapeutic agents listed in section.