JPS58159409A - Use of perfluorocarbon as injury medicine - 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 Many people sustain wounds of the type where healing of the injured tissue is usually limited by the amount of oxygen in the air to which the wound is exposed. Burns are a prime example, where the healing of injured tissue characteristic of burns is promoted by increasing the amount of oxygen in the injured tissue. Oxygen tents (high-density chambers) that surround the entire victim or burn area are used, but they pose safety issues and the oxygen exchange ratio and injured tissue are not very good, making it difficult for healing to occur. It was not entirely successful as it did not always eliminate the bacterial infections that tend to occur during periods.

The healing rate of many other types of wounds also increased as the amount of oxygen exposed to living cells in or around the injured tissue increased. These are not limited to relatively small wounds such as ordinary cuts, but also surgical excisions, bullet wounds, knife wounds, warts.

It also extends to bedsores, fractures where broken bones penetrate the skin, and various cuts and injuries from car accidents and other accidents. The most common such wounds are on the upper parts of the arms, legs, mouth, etc., i.e. on parts of the body that are easily exposed to the atmosphere.
The stomach, bones, and lungs can also receive similar injuries. For example, gastric ulcers, the actual area of a broken bone, etc., where the lack of oxygen slows down the rate of healing.

The above-mentioned wounds involve, among other things, discontinuities in body tissue.

Like an amputated finger, this discontinuity needs to be healed, and the survival of injured or dead tissue is proportional to oxygen availability. The above-mentioned wounds do not involve ordinary bruises, which are simply broken blood vessels that do not cause tissue discontinuities that produce black or dark marks.

Overall, burns are the most serious of the injuries mentioned above. These often cover large surfaces of the body in aggregates, but even individual burn areas are usually larger than the other wound areas mentioned above. Burns therefore deserve special mention.

A large number of people get burned every year. For example, one paper [Burn injury g J-Biomater, med, D
evices.

Artif, Organ86 (1), 1-35
, 1978, Bi Park (G,
A review done by John B. Park states that each year more than 2 million people in the United States suffer burns severe enough to require medical attention. About 7 more
0,000 people require hospitalization each year and 10,000
of people die as a result of their injuries.

The type of treatment for burns depends on the severity of the burn and the surface area affected. For severe burns, one method of treatment involves marginal excision, or removal of burnt tissue. Marginal resection includes surgical, mechanical or biochemical means. The latter may involve enzymatic margin resection using an oxygen detoxifying agent. These are proteolytic enzymes that selectively digest necrotic tissue without damaging adjacent viable tissue. Other marginal resections include the use of a tank filled with simple tap water maintained at an appropriate temperature and under strict sterile conditions. Once the person is in the tank, any dressings are removed and the burn is cleaned and debrided.

The person is then removed, covered with a sterilizing sheet, and transferred to an adjacent dressing room at an appropriate temperature and humidity.

- Removal of burned tissue poses certain problems. Besides being an effective barrier against harmful external substances, the human skin prevents the body from losing its water. According to Park's paper, such water loss can cause intense catabolism, which results in increased heat production, increased water loss and nitrogen consumption, weight loss, negative nitrogen balance, mostly from muscle, etc. manifests as a loss of cellular components. Strong catabolism is fatal and must therefore be minimized or regulated.

Again, according to Park's paper, another problem is that it is very important to produce clean, viable tissue suitable for tissue transplantation, and to ensure good initial tissue transplantation in patients with extensive burns. If this is not done, many lives may be lost.

Articles describing the treatments and problems mentioned above in more detail include: [Burns, initial evaluation and treatment] Router-7
7 (Luterman) CUTIS 12
2(4); 437-42. October, 78: Image preservation of burn wounds, ,=c 7 (Yarbo
rough, M, F, ) CUTIS
122 (41; 447-52, October 78; Advances in Fluid Treatment and Early Protection of Burn Patients, Zoruitobi, Nis, Jr. (Pruitt, B. S., Gr.)
World J, Surg, 2 (2); 139
-50.March 78; Handling of emergency burns - Cell.

Gursel, B. et al. JA
CKP 7 (5); 209-12゜May 78゜Water use during margin resection could be less than the desired amount. Water is difficult to maintain in a pure state. Microorganisms can easily reproduce therein. Drugs such as Hanaso, which are still used to prevent such reproduction, can have adverse effects on unprotected tissues. Water containing microorganisms can easily enter the body with consequent harmful consequences.

Burn victims who lack their normal skin barrier are thus exposed to contamination by water that comes into contact with their unprotected tissues. Furthermore, water can negatively affect the creation of a viable tissue area suitable for tissue transplantation by extracting beneficial components from the tissues in contact.

Much of the above discussion has been expressed in terms of human treatment = 9~, but such a limitation is not intended here. The burn treatment hereinafter claimed by applicant applies to animal burn victims and is not limited to humans.

New methods of treating burn victims include, but are not necessarily limited to, contacting the victim with a member of the class of oxygen-containing substances commonly known as synthetic blood or blood substitutes. The above categories include substantially fluorinated carbon materials including perfluorinated carbon having oxygen transport ability, substantially fluorinated carbon materials/perfluorinated carbon having oxygen transport ability, and The emulsion of the combination is admonished. Superfluorinated or dibrominated derivatives of carbon materials may also be used. The advantages of blood pumping are that it is non-toxic, can be saturated with oxygen during the day, can be easily kept sterile, and can be reused. It can also be easily maintained at a certain temperature, thereby providing for the comfort of the victim. It can be highly saturated with oxygen, thus promoting tissue healing. Furthermore, because of their physical and chemical properties, blood substances do not extract components from the tissue that are useful for successful tissue transplantation. It could also help avoid intense catabolism.

Another embodiment of the invention is the use of a dressing containing a synthetic blood substance that is brought into contact with a burn wound. Dressings may be particularly useful for small area burns. Other embodiments are disclosed later herein.

Useful preferred perfluorinated materials and methods for making them are disclosed in U.S. Pat. No. 4,105,798.

3.911.138 and 3,962,439. One particular member of the class of perfluorinated substances, namely perfluorinated decalin, is used as a blood cell substitute by Clark, L.C., Blood Substitutes and Plasma Expanders, 69- It is described in particular detail in the 80 page article Perfluorinated Decalin as a Red Blood Cell Substitute. However, substantially fluorinated or perfluorinated materials used in the treatment of humans with crab burns may have a certain vapor pressure range, such as that required if used as synthetic blood. and/or not limited to those having a retention time of spleen. Useful substantially fluorinated and perfluorinated materials are those that are generally in liquid form at temperatures and pressures suitable for contact with the victim, including ambient temperatures.

Examples of certain fluorinated materials suitable for use in the case of this invention include bicyclononane (e.g. bicycloC3,3,1
1 nonane, 2.6- ・dimethylbicyclo[3,3,1
1 nonane or 3-methylbicycloC3,3,11 nonane,) adamantane, methyl and dimethyladamantane,
Ethyladamantane, tetrahydrodicycloentanoene, methyl and schifmethylbicyclooctane, ethylmethyladamantane, ethyldimethyladamantane, tetrahydropinol S1 methyldiadamantane, triethyladamantane, triethyladamantane, pinene, camphene, 1,4,6.9- Tsumetanedecalin, bicyclo(4,3,21 undecane, bicyclo[5,3,01
cyclic substantially fluorinated or perfluorinated carbons, including substantially fluorinated or perfluorinated derivatives of C9C1B polycyclic compounds, such as (such as decane or mixtures thereof) It can include what is broadly described as hydrogen. Other examples include perfluorinated tributylamine, perfluorinated-2
-butyltetrahydrofuran and other commercially available perfluorinated ethers. Although some of the above compounds are solid at ambient temperature, they are soluble in those that are liquid at ambient temperature, and such mixtures can be used. Perfluorinated materials below C8 and materials up to C1 or higher may be used in this invention. Mixtures of different perfluorinated materials may also be used. Certain precursors of the foregoing perfluorinated carbons are of no use for this purpose, but are the corresponding organic compounds in which most of the hydrogen atoms are replaced by fluorine.

Perfluorinated means that substantially all hydrogen atoms in the carbon material have been replaced with fluorine atoms. However, although the perfluorinated materials mentioned above (also Havel fluorocarbons) are preferred, substantially fluorinated carbon materials can also be used in this invention. Substantially fluorinated means that most of the hydrogen atoms are replaced with fluorine atoms and further substitutions do not substantially increase the oxygen transport capacity of the material. This level is believed to be reached when about 80 to 90 hydrogen atoms are replaced by fluorine atoms. −
U.S. Patent No. 3,911.1.38
and 4,105.798 The effort to transport oxygen in an IC is related to the solubility of oxygen in the material. These U.S. patents state that perfluorinated substances are
It will absorb 10-100 CC of oxygen per 0C.

The solubility of +H1 is at 5°C and 7601 columns of mercury. Substantially fluorinated carbon materials that may be used in the present invention will have similar oxygen transport capabilities.

Also, some of the fluorine atoms in the above materials may be replaced with other halogen atoms such as bromine. These compounds include, for example, monobrominated compounds such as 1-tadecafluoro-bromide, 4-isoderobylcyclohexane, 3-isozorobyl-cyclopentane, or tribrominated compounds thereof. Brominated derivatives are included.

14- Perfluorinated as indicated means that substantially all ten hydrogen atoms of the carbon material have been replaced by fluorine atoms (or in the case of the mono- or dibromo derivatives listed below) (also by the bromine atom). At least 95φ
Preferably, the hydrogen atoms are substituted, more preferably at least 08 and even more preferably essentially 100.

Oxygen can be added to substances by many different means. An example would be bubbling 1.004 oxygen through the material.

The substantially fluorinated carbon material used in the treatment of burn victims may also include the substantially fluorinated carbon material or a brominated derivative thereof, water, a suitable emulsifier and any other additives such as antibiotics. It may be in the form of an emulsion containing physiologically acceptable substances. The high oxygen content of this perfluorinated carbon can prevent or reduce microbial growth in the water of the emulsion. The production of such emulsions, selection of emulsifiers, and relative amounts of ingredients are described in more detail in the above-mentioned U.S. Patent No. 4.
H15798, which is incorporated herein by reference. The emulsion used in the practice of this invention may also be a substantially fluorinated carbon material of 1'f4 or greater.

Any material used at the same time to treat burn areas in the practice of this invention may be applied to any substantially fluorinated carbon material or (or towed derivative emulsion or combination thereof) used. Examples of drugs previously used to prevent or eliminate sexually transmitted infections include silver nitrate, antibiotics, and the enzymes previously mentioned. Also, if the burn was caused by a chemical, the harmful chemical must be completely removed from the victim prior to or in conjunction with the use of perfluorinated carbon.

Contacting a burn victim with perfluorinated carbon can be done in a variety of ways. For example - embodiments include immersing the victim in a bath of the substance maintained at an appropriate comfortable temperature. If necessary, the material is recycled through purification means to remove tissue and other materials coming from the victim. Immersion may also include the use of a container such as a plastic bag resulting in immersion of a portion of the victim's length, such as a hand, arm or leg. The length of immersion depends in part on the condition of the victim and the judgment of the medical practitioner. One advantage of using a self-contained substance for contact, especially when immersed, is that it aids in regulating the body's water that is lost through the exposed tissue and thereby avoids strong catabolic effects. It is also a scale. Another purpose of contact is to bounce off the underlying wound bed prior to contact. Obviously, if there is excess material left on the wound, it will not be possible to connect it properly.

Perfluorinated carbon (or its brominated derivative)
Contacting can also be achieved by using a lubrication containing the substance.

The purpose of the dressing is to impregnate the wound with perfluorinated carbon. The plastic bag can achieve this, but
Dressings are usually applied directly to the wound or at least adjacent to tissue and the wound.

Perfluorinated carbon in the dressing may help avoid sticking problems, especially if its vapor pressure is relatively low and it does not evaporate easily.

17- The liquid will lubricate the tissue and dressing and avoid any problems caused by dryness. The dressing can be applied directly to the burn itself or it can be a sheet that contacts a large area of the victim. Dressing, as used herein, is broadly defined to include any suitable material that is brought into contact with a victim. Although it may be assumed that the dressing is equivalent to a sponge or gauze in the concept of a loosely woven cotton surgical dressing, no such limitation is intended. EXAMPLES The f-ird 1/tushing may be a foam containing a blood group substance, a stripe or kale, lyophilized pig skin or other suitable animal material.

Usually pigskin must be reconstituted by soaking in a suitable solution of sterile salt or some other or perfluorinated carbon itself before use as a foreign body implant.

Instead of solutions of sterilizing salts or others, the pigskin is reconstituted using a substantially fluorinated carbon material or its brominated derivative or an emulsion combination thereof.

As used herein, "contacting" refers to external use as opposed to internal use of certain perfluorinated materials as blood 18-substitutes.

The contact used here refers to topical application and excludes the use of perfluorinated carbon in blood vessels. Contact is often by application to the skin surface as described above. However, this does not exclude application to areas other than the skin surface, except for blood vessels. Examples of the latter applications include exposing bone tissue through surgery, applying to the stomach using a tube, and applying to the respiratory mucosal surface using a tube.

Applicant: Santic Incorporated l]-1 Agent: Patent attorney Shota Sasai 1□ (19-

Claims (1)

Claims: A method of treating a victim with a wound whose normal healing is promoted by exposure to oxygen, the method comprising: a substantially fluorinated carbon material containing molecular oxygen; or a method comprising contacting the wound with an effective amount of a fluid containing a dibromo derivative, wherein the contact is by means other than blood vessels. 2. The method according to claim 1, wherein the wound is a burn. 3. The method of claim 1, wherein the substantially fluorinated carbon material or its @conductor is derived from a cyclic hydrocarbon. 4. Claim fJ in which the treatment is applied to the surface of the skin
1.2 or 3 method. 5. The method of claim 4, wherein the liquid contains a compatible drug. 0. The method according to claim 3, wherein marginal resection is performed before treatment. 7. An article useful for treating wounds whose healing is normally accelerated by exposure to oxygen, the article comprising molecular oxygen;
An article consisting of a dressing containing an active substance of a liquid comprising a substantially fluorinated carbon material or a mono- or dibromo derivative thereof. 8. The article of claim 7, wherein the substantially fluorinated carbon or derivative thereof is derived from a cyclic hydrocarbon. 9 Claim 7 in which the liquid also contains a compatible drug
Items in Section. IQ, a substance that is liquid at ambient temperature and pressure and has the ability to absorb oxygen, a practically fluorinated carbon material or a mono- or di-bromo derivative thereof, an emulsion containing that material; A method of treating burn injuries comprising contacting the wound with an effective amount of a substance from the group consisting of a combination thereof. 11. Claim 10, wherein the substantially fluorinated carbon is a perfluorinated carbon material.
Section method. 12. Claim 10 in which the burn patient is a human being
Section method. 13. A substantially fluorinated carbon material or a heptano or di-bromo derivative thereof which is liquid at ambient temperature and pressure and is capable of absorbing oxygen; (b) an emulsion containing this material; An article useful for the treatment of burns comprising a gauze or sponge dressing containing an effective amount of a substance selected from the group consisting of combinations thereof. 14. The article of claim 13, wherein the substantially fluorinated carbon material is a perfluorocarbon material. 15. In methods of treating burn victims, including marginal excision, the patient is exposed to substantially fluorinated carbon substances or di-brominated derivatives having oxygen-carrying capacity; A method comprising contacting the victim with a liquid material selected from the group consisting of emulsions containing and combinations thereof. ]6. 15. The improvement of claim 14, wherein the substantially fluorinated carbon material is a perfluorocarbon material. 17 Emulsions containing substantially fluorinated carbon materials or mono- or dibromo derivatives thereof, which are liquid at ambient temperature and pressure and capable of absorbing oxygen, and combinations thereof; A composition useful for treating burns in the form of a foam, spray or gel containing an effective amount of a substance.