When was silvadene invented

Effective silver sulfadiazine-containing compositions in accordance with this invention having the formulation of Example No.

Effective silver sulfadiazine-containing compositions in accordance with this invention having the formulation as set forth in Example No. Effective silver sulfadiazine-containing compositions in accordance with this invention in accordance with the formulation of Example No.

Effective silver sulfadiazine-containing compositions in accordance with this invention are prepared with the formulation of Example No. Effective, very soft cream-like silver sulfadiazinecontaining compositions in accordance with this invention are prepared according to the formulation of Example No. Effective silver sulfadiazine-containing composition in accordance with this invention are prepared with the formulation of Example No.

In the preparation of the silver sulfadiazinecontaining compositions in accordance with this invention wherein the silver sulfadiazine is dispersed in a water-dispersible, hydrophilic ointment or carrier, such as a water-dispersible, oil-in-water emulsion, various techniques may be employed. The technique described hereinabove in connection with Example No.

If desired, dry, finely divided silver sulfadiazine, such as micronized silver sulfadiazine wherein about percent of the silver sulfadiazine particles having a particle size below microns, may be added or otherwise homogeneously incorporated in the desired waterdispersible, hydrophilic ointment to provide the silver sulfadiazine compositions. Finely divided silver sulfadiazine having a particle size, smaller or larger, than the aforementioned particle size, is useful in the practice of this invention.

For example, silver sulfadiazine having the following particle size analyses are usefully employed in the practice of this invention for the preparation of effective silver sulfadiazine-containing compositions:. Silver Sulfadiazine Batch No. As indicated hereinabove, the composition of the water-dispersible hydrophilic ointment base or carrier for the silver sulfadiazine may vary.

Numerous suitable commercially available hydrophilic or waterdispersible removable ointments or carriers are available. For example, the following hydrophilic or oil-inwater emulsion bases are available and suitable in the preparation of silver sulfadiazine-containing compositions in accordance with this invention, Neobase manu factured by Burroughs-Wellcome, Unibase manufactured by Parke-Davis, Emulsion Base manufactured by Almay, Dermabase manufactured by Marcelle, Cetaphil manufactured by Texas Pharmacel, Multibase manufactured by Ar-Ex, Vanibase manufactured by Warren-Teed and Solucream manufactured by Lascoff.

In general, hydrophilic bases, such as hydrophilic bases of the oil-in-water emulsion type are characterized by the case which they may be removed from the skin by washing with water. Useful in thepreparation of silver sulfadiazinecontaining compositions in accordance with this invention is the water-dispersible hydrophilic oil-in-water emulsion ointment sold under the tradename Neobase.

Neobase is a semi-solid, oil-in-water emulsion base which is water-miscible, slightly acid aqueous mixture has a pH 5. When an ointment containing silver-sulfadiazine dispersed in a water-washable or water-dispersible hydrophilic carrier, as exemplified by an ointment comprising l percent by weight silver sulfadiazine dispersed in a hydrophilic carrier, e.

Neobase, is applied to a very tender area, such as a raw wound or an opened burn surface or granulation there is no pain felt whatsoever. Rather, the application of the silver sulfadiazine ointment in accordance with this invention is pleasurable and feels good to the patient and appears to have anesthetic properties.

This pleasurable and good feeling is in contrast to the sharp pain usually felt when Sulfamylon ointment or other such medicaments are applied. By way of explanation, the soothing effect experienced when a silver sulfadiazine-containing ointment is applied to a raw wound or an open burn may be due to the fact that the silver sulfadiazine is insoluble and is in suspension and not in solution and does not appear to dissolve in the body fluids except only gradually.

The insolubility of silver sulfadiazine which might appear first to be a disadvantage thus appears to be an advantage when topically applied to a burned surface. When patients having large burns are dressed with a silver sulfadiazine-containing hydrophilic ointment in accordance with this invention, such as an ointment or dressing made up of Neobase and containing about percent by weight sliver sulfadiazine, no morphine or other pain relieving drug need be given prior to dressing changes.

This is in marked contrast with other forms of local therapy. Gauze bandages impregnated with a silver sulfadiazine ointment as described herein do not adhere to burned skin surfaces even after two or three days. In contrast, Vaseline coated and other bandages when applied to burned skin surfaces become adherent and it is often necessary to forcefully pull the gauge bandages away from the wound.

This causes severe pain and for this reason morphine is usually given to the patient in such instances prior to dressing change. In contrast, dressing coated with or impregnated with a silver sulfadiazine-containing ointment in accordance with this invention, such as a bandage impregnated with silver sulfadiazine dispersed in a hydrophilic ointment, are painless when removed.

Indeed, a silver sulfadiazine-containing ointment in accordance with this invention because this application is painless and even pleasurable can readily and generously be applied and rubbing the ointment over the raw tissue even in the instance of large burns. In vitro tests demonstrating the efficacy of the silver anti-bacterial agents of this invention were carried out. In these tests 0. The test squares were placed on plain nutrient agar inoculated with various strains of Pseudomonas aeruginosa isolated from hospital patients.

Of the 13 strains of Pseudomonas aeruginos tested all were inhibited. In vivo tests were also carried out to demonstrate the effectiveness of silver sulfadiazine in burn therapy. In these tests scalded mice contaminated with Pseudomonas aeruginosa were employed. The scaled mice were contaminated by dipping their tails in a solution of an overnight broth culture of Pseudomonas aeruginosa. Local therapy was initiated several hours later by either immersing the mice into a 0. After a few preliminary trails of more frequent treatment these experiments were conducted by a once-daily application of the ointment or dipping into the solution or sus-pension.

The mice were kept in cages with wood shavings which were changed daily. After death of the mice, cultures of the heart blood were made in some instances. These tests were positive to Pseudomonas.

Typical experiments after a small burn tail and both thighs , about percent of the body surface area, and large burns, approximately percent of the body surface area, are shown in N In accompanying Table II in vivo test results are summarized.

Aeruginoaa culture dilutlon. Local therapy begun hours after llflllttlgt and daily for 8 days or more] Death, days after burn- Total 1n0r- No. Aerugz'nosa do not succumb. Data were also obtained in similar tests carried out with other organisms, such as Staphylococcus aureus.

The superiority of the silver sulfadiazine in terms of increased and prolonged survival as reported in accompanying Table II and illustrated in FIGS. The tissues and fur of the mice treated with silver nitrate darkened. With respect to the few mice surviving without any anti-bacterial therapy the separation of the eschar did not occur within three weeks.

In other experiments which were terminated within three weeks similar evidence of healing appeared. In two experiments therapy was discontinued after seven days in one-half of the surviving mice, see FIG. In many instances, mortality increased suddenly suggesting either reinfection or persistence of virulent organisms. Daily tubing in water or saline solution with removal of crusts and nectrotic tissue as done in man would undoubtedly improve the results and prevent reinfection.

In some experiments the length of viable tail was measured. The results of these tests are shown in accompanying Table Ill:. Average of few survivors See Table II These results only partially reveal the superiority of silver sulfadiazine. These results demonstrate that postburn infection plays a major role in causing considerable loss of skin and muscle from tails and extremities.

In tests an ointment containing 1 percent by weight silver sulfadiazine in a water-soluble hydrophilic base, e. Toxicity of silver sulfadiazine as judged in burned mice treated with 1 percent by weight silver sulfadiazine suspension or ointment was not apparent. Absorption was evaluated by excretion of sulfadiazine in the urine after implanation in the cutaneous tissues of dogs. Doses of mg. These low values are in marked contrast to the high levels obtained after implantation of the soluble sodium salts.

After application of gm of the 1 percent by weight silver sulfadiazine ointment to 1 square meter burned surface in patients the blood levels of sulfadiazine ranged from 2. This represents from 4 to 13 percent of the total amount applied to the burned surfaces. Intraperitoneal injection of the suspension of silver sulfadiazine causes convulsions and death after 0.

These experiments were conducted in parallel with equimolar solutions of silver nitrate and the toxicity values were found to be identical. Silver sulfadiazine is non-toxic when applied topically and this is in accordance with observations already made with respect to other topically applied silver compounds. The results of these tests indicate that burned mice are highly susceptible to contact infection with Pseudomonas aeruginosa.

The once-daily local application of 0. In contrast the local application once-daily of a hydrophilic ointment containing 1 percent by weight of silver sulfadiazine reduced the mortality of between 5 percent and 20 percent in eight days or longer in numerous experiments involving approximately mice.

In addition, post-burn destruction of skin and muscle by infection was greatly diminished in surviving mice treated with the silver sulfadiazine ointment. These experiments indicate that in burned mice infected with Pseudomonas aeruginosa silver sulfadiazine is superior to other agents in terms of overall survival, wound-healing and absence of toxicity and with no staining of tissues.

The material is produced via an ion-exchange process where sodium is replaced by silver. When this material is used in wound care, sodium in the wound exudate binds to the dressing, causing a release of silver from the dressing fibers.

Tests have shown that for P. Ionic silver can be adsorbed or trapped into or onto materials. Two forms of these technologies are currently in the market - silver charcoal and silver zeolite products. Silver charcoal. This technology utilizes silver adsorbed on organic matter that is converted to charcoal through a high temperature process. These materials do not release silver into the medium, but are intended to kill organisms that are adsorbed onto the charcoal.

Metallic silver. A variety of metallic silver-containing products are on the market today. Metallic silver deposition technologies include electroless plating, vacuum deposition, and ion implantation processes.

Nanocrystalline silver. Nanocrystalline silver coatings are a recent innovation in metallic silver processing. From a materials perspective, a nanocrystalline material has a crystal size less than 20 nm. These changes are due, in part, to the increase in the volume of the crystal or grain boundary relative to the crystal bodies. Birringer25 suggested that the grain boundary region may represent a new state of solid matter.

The traditional states of solid matter are amorphous and crystalline states. Amorphous matter, where the atoms and molecules interact with their nearest neighbor, and crystalline matter, where atoms and molecules interact with the atoms and molecules of the crystal lattice, have short-range and long-range order, respectively.

Atoms and molecules that reside in grain boundaries are influenced by the adjacent grains, but because they are not part of the crystal structure, they have no long-range order. Further, they are unable to interact with neighbor atoms or molecules because of the effects of the adjacent grains and, therefore, may have no order at all. The nanocrystalline-derived silver is bactericidal to a wide range of bacteria, antibiotic resistant bacteria see Figure 2 and fungi.

Since then, other noble metals have been used clinically for their anti-inflammatory or anti-inflammatory like properties. Gold chloride is used as an intra-articular injectable for the treatment of rheumatoid arthritis because of its potent anti-inflammatory properties.

The nanocrystalline form of silver has increased the ways in which silver is released. A recent paper evaluated matrix metalloproteinases MMP , cell apoptosis, and healing in a porcine model where wounds were dressed with nanocrystalline silver dressing, silver nitrate, and saline soaks.

A recent pilot clinical study29 examined the composition of venous ulcer wound fluids in wounds treated with the nanocrystalline silver dressing and a control.

The authors report that, in this patient study five treated with the nanocrystalline silver dressing and five control , MMP-9 and TNF-alpha levels were suppressed relative to the controls. Demling and DeSanti30 have shown that meshed autografts in the clinic re-epithelialize faster when treated with nanocrystalline silver dressings than when treated with a petrolatum-impregnated gauze with moist neomycin compresses.

This finding was supported by Olson's31 earlier work on porcine donor sites. Voigt and Paul32 have used nanocrystalline silver dressings extensively and are currently studying re-epithelialization of donor sites as well as a variety of other applications.

No other forms of silver have generated the types of wound responses observed in preclinical and clinical studies with nanocrystalline silver dressings. This is consistent with Demling and DeSanti's2 position that the form of silver and the choice of carriers are important. Conclusion Silver is a powerful antimicrobial agent that is susceptible to inactivation through chemical complexation. Past treatment protocols compensated for large losses of silver ions by providing large excesses of replacement silver at frequent intervals which, while efficacious, also created problems for healthcare providers and patients.

New materials such as nanocrystalline silver are opening new research areas on silver and all of its biological properties. Not only will silver provide excellent antimicrobial protection, but it also may enhance wound closure. Only more research will provide the answers. Sheila Talton, president and chief executive officer, Gray Matter Analytics. Sign in. Podiatry Today. Today's Wound Clinic. Symposium on Advanced Wound Care. Current Research. Author Instructions. Editorial Board.

Contact Us. Advertising Opportunities. Print Subscription. Renew Print Subscription. Copied to clipboard. Submit Feedback. Email Address. Silvadene cream. Topical antimicrobials for burn wound infections. Recent Pat Antiinfect Drug Discov. National Institue of Health. Persistent lactic acidosis after chronic topical application of silver sulfadiazine in a pediatric burn patient: a review of the literature. Int J Burns Trauma. A modern method of treatment: The role of silver dressings in promoting healing and preventing pathological scarring in patients with burn wounds.

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