EP0324802A1 - Method for the treatment of body tissues and the administration of drugs thereto - Google Patents

Method for the treatment of body tissues and the administration of drugs thereto

Info

Publication number
EP0324802A1
EP0324802A1 EP88903116A EP88903116A EP0324802A1 EP 0324802 A1 EP0324802 A1 EP 0324802A1 EP 88903116 A EP88903116 A EP 88903116A EP 88903116 A EP88903116 A EP 88903116A EP 0324802 A1 EP0324802 A1 EP 0324802A1
Authority
EP
European Patent Office
Prior art keywords
oxygenated
perfluorocarbon
fluid
drugs
tissue
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.)
Withdrawn
Application number
EP88903116A
Other languages
German (de)
French (fr)
Other versions
EP0324802A4 (en
Inventor
Edward S. Neiss
Charles G. Smith
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.)
Abeona Therapeutics Inc
Original Assignee
Chemex Pharmaceuticals Inc
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
Application filed by Chemex Pharmaceuticals Inc filed Critical Chemex Pharmaceuticals Inc
Publication of EP0324802A1 publication Critical patent/EP0324802A1/en
Publication of EP0324802A4 publication Critical patent/EP0324802A4/en
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/02—Halogenated hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/02—Halogenated hydrocarbons
    • A61K31/025—Halogenated hydrocarbons carbocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the invention relates to a method for a treatment of and the administration of drugs to body tissues and surfaces.
  • this invention particularly relates to the treatment of structures such as the skin or mucosa which are in need of enhanced or supplemental oxygen supply.
  • This invention also relates to the treatment of individuals or tissues within individuals which may additionally or alternatively require the administration of drugs.
  • Yet another long sought goal of medical science is ' an effective, non-invasive technique for the percutaneous administration of drugs.
  • Most known methods are not well suited to be used by patents (e.g., intraveneous injection) or result in poor absorption and utilization of the drug (e.g., enceric administration). It is therefore an object of this invention to provide a method of treatment which will supplement or restore the-;; oxygen supply to damaged tissues. It is also an object of this invention to provide a method of treatment which facilitates the effective percutaneous administration of drugs which can be useful in the treatment of disease and especially useful in the treatment of damaged or diseased mucosa or skin.
  • damaged bodily tissue is treated by oxygenating a pharmaceutically acceptable liquid with a therapeutically effective amount of oxygen and then applying the oxygenated liquid to the affected tissue.
  • another therapeutic agent is dissolved or suspended in the liquid in addition to • or in place of oxygen.
  • This therapeutic agent may be selected from an exceptionally wide variety of drugs including antibiotics, anti-inflamatories or mixtures of such agents or drugs.
  • Another highly useful group of therapeutic agents are those which are useful in treating skin diseases such as acne, psoriasis, angina pectoris or skin cancers.
  • perfluorinated hydrocarbons are generally insoluble in water it is highly preferred that an aqueous emulsion of the perfluorinated hydrocarbons to be used.
  • Fluosol-DA Green Cross
  • Oxypherol-ET Alpha Therapeutic Corporation. The composition of Oxypherol-ET is set forth in Table II.
  • the Oxypheral-ET formulation may be modified by increasing the hydroxyethyl starch level to from 5- to 20%.
  • the oxygenation of the perfluorocarbon or perfluorocarbon emulsion used in the process of the present invention can be carried out by exposing the fluid to an atmosphere of at least 75% oxygen, although an atmosphere of at least 95% oxygen is preferred. This is most effectively accomplished by bubbling oxygen at slightly greater than atmqspheric pressure through the perfluorocarbon. Once oxygenated, the perfluorocarbon or perfluorocarbon emulsion may be applied directly to damaged tissue.
  • Perfluorocarbon preparations are known to be able to dissolve at least 40% of oxygen and it is desirable to use fully saturated preparations when treating oxygen starved tissues. However, even oxygen starved tissues benefit substantially from the use of 25% solutions.
  • the oxygenated fluid should be applied to the affected tissue at regular intervals to obtain maximum therapeutic effect. It is expected that it will be necessary to reapply the oxygenated fluid to the affected tissue 2 to 6 times each day.
  • topical or percutaneous administration of drugs can be accomplished with special advantage by the process of the present invention and the absorption of drugs is accomplished with suprising effectiveness.
  • the affected tissue has suffered injury as a result of a trama or where secondary infection is present or seriously possible, it will be advisable to include a therapeutic concentration of an appropriate antibotic in the oxygenated perfluorocarbon fluid.
  • Therapeutic concentrations of some suitable topical antibotics are set forth in Table III.
  • Polymyxin B 0.5-1.5% by wt.
  • an anti-inflamatory agent may be included in the oxygen-containing liquid which is used in the present invention.
  • an anti-inflamatory agent may be included in the oxygen-containing liquid which is used in the present invention.
  • hydrocortisone 0.5 to 1.5% by weight
  • Other therapeutic agents which may be used include nordihydroquaiaretic acid and its derivatives, the usefulness of which is described in co-pending United States Patent Application No. 699,923, filed February 2, 1985.
  • a wide variety of drugs can be administered with exceptional effectiveness through healthy skin by the process of the present invention. This process, therefore, has broad application in the percutaneous administration of drugs without regard to its usefulness as an oxygen supply technique.
  • a bedsore may be treated by applying to it sufficient volume of oxygenated Oxypherol-ET to completely over the sore.
  • the sore can be seen to begin to heal within 2 weeks and heal completely in about 4 weeks as the above described procedure is repeated every 12 hours.
  • nitroglycern can be dissolved in the above-mentioned perfluorocarbon composition and applied in a patch on the skin of a patient suffering from angina pectoris. This procedure can provide immediate and sustained relief to the patient.
  • Oxypherol-ET oxygenated Oxypherol-ET to completely over the sore.
  • the sore can be seen to begin to heal within 2 weeks and heal completely in about 4 weeks as the above described procedure is repeated every 12 hours.
  • nitroglycern can be dissolved in the above-mentioned perfluorocarbon composition and applied in a patch on the skin of a patient suffering from angina pectoris. This procedure can provide immediate and sustained relief to the patient.

Abstract

An oxygenated fluid is applied to damaged bodily tissue, thereby making oxygen available to the tissue. Perflurinat­ ed hydrocarbons may be oxygenated and used in this process. Various therapeutic agents may be mixed with the oxygenat­ ed fluid and administered to the damaged tissue.

Description

METHOD FOR THE TREATMENT OF BODY TISSUES AND THE ADMINISTRATION OF DRUGS THERETO
The invention relates to a method for a treatment of and the administration of drugs to body tissues and surfaces. In one embodiment, this invention particularly relates to the treatment of structures such as the skin or mucosa which are in need of enhanced or supplemental oxygen supply. This invention also relates to the treatment of individuals or tissues within individuals which may additionally or alternatively require the administration of drugs.
Medical science has long sought effective methods of treatment for body tissues which suffer from inadequate oxygen supply. Often this inadequate oxygen supply is the result of chronic circulatory problems and the like. Examples of such conditions include bed sores, diabetic skin ulcers and ulcers which are associated with atherosclerotic conditions. At other times, this oxygen starved condition can be caused by a tramatic injury which interrupts or diminishes the blood supply to a part of the body. Failure to treat these sorts of conditions can result in slow or failed healing, scarring, large scale tissue necrosis and even gangrene. Secondary infections can always be a serious problem in these situations.
Yet another long sought goal of medical science is 'an effective, non-invasive technique for the percutaneous administration of drugs. Most known methods are not well suited to be used by patents (e.g., intraveneous injection) or result in poor absorption and utilization of the drug (e.g., enceric administration). It is therefore an object of this invention to provide a method of treatment which will supplement or restore the-;; oxygen supply to damaged tissues. It is also an object of this invention to provide a method of treatment which facilitates the effective percutaneous administration of drugs which can be useful in the treatment of disease and especially useful in the treatment of damaged or diseased mucosa or skin.
According to this invention, damaged bodily tissue is treated by oxygenating a pharmaceutically acceptable liquid with a therapeutically effective amount of oxygen and then applying the oxygenated liquid to the affected tissue. In an alternate embodiment of the invention another therapeutic agent is dissolved or suspended in the liquid in addition to • or in place of oxygen. This therapeutic agent may be selected from an exceptionally wide variety of drugs including antibiotics, anti-inflamatories or mixtures of such agents or drugs. Another highly useful group of therapeutic agents are those which are useful in treating skin diseases such as acne, psoriasis, angina pectoris or skin cancers.
There are several -compounds which are known to be pharmaceutically acceptable liquids capable of dissolving therapeutically effective amounts of oxygen. These compounds have in the past been known to be useful only as blood replacements. That is, they are used as a temporary supplement to the body's supply of blood when blood is lost through tramatic injury or surgery. These compounds are almost always perfluorinated hydrocarbons. A list of perfluorinated hydrocarbons which can be used in the process of the present invention is set forth in Table I. TABLE I
perfluordecalin perfluoro, 1-methydecalin perfluorotributylamine perfluorotribyltetrahydrofuran perfluoropolyether perfluorotripropylamine perfluorodihexylether perfluoro,4-methyloctehydroquinolidizine
Because perfluorinated hydrocarbons are generally insoluble in water it is highly preferred that an aqueous emulsion of the perfluorinated hydrocarbons to be used. A number of emulsified perfluorinated hydrocarbons .are commercially available as blood replacements. Examples include Fluosol-DA (Green Cross) a mixture of fluorinated decalin and perfluor¬ inated tripropylamine. Another highly preferred commercially available material is Oxypherol-ET (Alpha Therapeutic Corporation). The composition of Oxypherol-ET is set forth in Table II.
*A polyoxyethylene-polyoxypropylene. e ulsifier. While these commercially available perfluorocarbon preparations are well suited to use in this invention/ it is often helpful to increase their viscosity by using a greater proportion of thickening agents. Thus, the Oxypheral-ET formulation may be modified by increasing the hydroxyethyl starch level to from 5- to 20%.
The oxygenation of the perfluorocarbon or perfluorocarbon emulsion used in the process of the present invention can be carried out by exposing the fluid to an atmosphere of at least 75% oxygen, although an atmosphere of at least 95% oxygen is preferred. This is most effectively accomplished by bubbling oxygen at slightly greater than atmqspheric pressure through the perfluorocarbon. Once oxygenated, the perfluorocarbon or perfluorocarbon emulsion may be applied directly to damaged tissue.. Perfluorocarbon preparations are known to be able to dissolve at least 40% of oxygen and it is desirable to use fully saturated preparations when treating oxygen starved tissues. However, even oxygen starved tissues benefit substantially from the use of 25% solutions.
The oxygenated fluid should be applied to the affected tissue at regular intervals to obtain maximum therapeutic effect. It is expected that it will be necessary to reapply the oxygenated fluid to the affected tissue 2 to 6 times each day.
Owing to the physical and chemical characteristics of the perfluorinated hydrocarbons used in the method of the present invention, topical or percutaneous administration of drugs can be accomplished with special advantage by the process of the present invention and the absorption of drugs is accomplished with suprising effectiveness. Thus, where the affected tissue has suffered injury as a result of a trama or where secondary infection is present or seriously possible, it will be advisable to include a therapeutic concentration of an appropriate antibotic in the oxygenated perfluorocarbon fluid. Therapeutic concentrations of some suitable topical antibotics are set forth in Table III.
TABLE III
Bactracin 400-600 units/gm
Chloramphenicol 0.5-1.5% by wt.
Gentamycin 0.5-1.5% by wt.
Polymyxin B 0.5-1.5% by wt.
Natamycin 3.0-7.0% by wt.
Oxytetracycline 1.0-2.0% by wt
Similarly, if inflamation of the affected tissues is or may be a significant problem, an anti-inflamatory agent may be included in the oxygen-containing liquid which is used in the present invention. For example, 0.5 to 1.5% by weight of hydrocortisone may be used. Other therapeutic agents which may be used include nordihydroquaiaretic acid and its derivatives, the usefulness of which is described in co-pending United States Patent Application No. 699,923, filed February 2, 1985. Also, a wide variety of drugs can be administered with exceptional effectiveness through healthy skin by the process of the present invention. This process, therefore, has broad application in the percutaneous administration of drugs without regard to its usefulness as an oxygen supply technique.
As a non-limiting example of the present invention, a bedsore may be treated by applying to it sufficient volume of oxygenated Oxypherol-ET to completely over the sore. The sore can be seen to begin to heal within 2 weeks and heal completely in about 4 weeks as the above described procedure is repeated every 12 hours.
In yet another example of this invention, nitroglycern can be dissolved in the above-mentioned perfluorocarbon composition and applied in a patch on the skin of a patient suffering from angina pectoris. This procedure can provide immediate and sustained relief to the patient.
oxygenated Oxypherol-ET to completely over the sore. The sore can be seen to begin to heal within 2 weeks and heal completely in about 4 weeks as the above described procedure is repeated every 12 hours.
In yet another example of this invention, nitroglycern can be dissolved in the above-mentioned perfluorocarbon composition and applied in a patch on the skin of a patient suffering from angina pectoris. This procedure can provide immediate and sustained relief to the patient.

Claims

WHAT IS CLAIMED IS:
1. A method of creating damaged bodily tissue comprising the steps of
Oxygenating a pharmaceutically acceptable fluid and
Applying the oxygenated pharmaceutically acceptable fluid to the damaged bodily tissue.
2. The process of' claim 1 wherein said pharmaceuticall~y acceptable fluid is an aqueous emulsion of a perfluoronated hydrocarbon and said tissue is skin or mucosa.
3. Th'e process of claim 2 wherein said oxygenated fluid contains at least 25.0 volume percent oxygen.
4. The process of claim 3 wherein said oxygenated fluid contains an additional therapeutic agent selected from the group consisting antibiotics, anti-inflamatory agents and mixtures of antibiotics, and anti-inflamatory agents.
5. The process of claim 3 wherein said oxygenated fluid contains an additional therapeutic agent sleeted from the group consisting of nordihydroquiraretic acid and its pharmaceutically acceptable derivatives.
6. A method of administering at least on drug to an individual requiring treatment comprising the steps of
mixing an efficacious amount of at least one drug with a perfluorocarbon compound
applying the drug mixed with the perfluorocarbon to the skin or mucosa of the individual requiring treatment.
7. The method of claim 6 wherein said perfluorocarbon is in the form of an emulsion.
EP19880903116 1986-09-19 1987-08-18 Method for the treatment of body tissues and the administration of drugs thereto Withdrawn EP0324802A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US90983286A 1986-09-19 1986-09-19
US909832 1986-09-19

Publications (2)

Publication Number Publication Date
EP0324802A1 true EP0324802A1 (en) 1989-07-26
EP0324802A4 EP0324802A4 (en) 1991-07-24

Family

ID=25427897

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19880903116 Withdrawn EP0324802A4 (en) 1986-09-19 1987-08-18 Method for the treatment of body tissues and the administration of drugs thereto

Country Status (4)

Country Link
EP (1) EP0324802A4 (en)
JP (1) JPH01503146A (en)
AU (1) AU2807689A (en)
WO (1) WO1989000848A1 (en)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5284645A (en) * 1987-08-05 1994-02-08 Alliance Pharmaceutical Corp. Fluorocarbon emulsions containing amino acid based anti-inflamatory agents and buffer systems
US5847009A (en) 1986-01-14 1998-12-08 Alliance Pharmaceutical Corp. Prophylaxis in the parenteral administration of particulate dispersions in fluorocarbon emulsions
US5061688A (en) * 1988-08-19 1991-10-29 Illinois Institute Of Technology Hemoglobin multiple emulsion
DE4100059C2 (en) * 1991-01-03 1994-08-25 Adatomed Pharma & Med Treatment liquid for reapplication (detached) of detached retina to the choroid of the eye
US5200430A (en) * 1991-03-21 1993-04-06 Escalon Ophthalmics, Inc. Debridement of bodily cavities using debridement fluids
US5643601A (en) * 1992-06-26 1997-07-01 Lancaster Group Ag Phospholipid-and fluorocarbon-containing cosmetic
DE4221268C2 (en) * 1992-06-26 1997-06-12 Lancaster Group Ag Use of a dermatological to support the oxygen transport in the skin
US5641509A (en) * 1992-06-26 1997-06-24 Lancaster Group Ag Preparation for topical use
DE4221256C2 (en) * 1992-06-26 1997-07-10 Lancaster Group Ag Galenic composition for topical use
WO1994023748A1 (en) * 1993-04-08 1994-10-27 The University Of Queensland Administration of vaso-active agent and therapeutic agent
GB9308280D0 (en) * 1993-04-21 1993-06-02 Stead Gordon Thickening of fluorinated liquids
US5470885A (en) * 1993-09-29 1995-11-28 The Research Foundation Of The State University Of New York Fluorocarbons as anti-inflammatory agents
CA2176220A1 (en) * 1993-11-15 1995-05-26 Elizabeth Anne Woodcock A method for treating cardiac dysfunction and pharmaceutical compositions useful therefor
DE4405627A1 (en) * 1994-02-22 1995-08-24 Hoechst Ag Oil emulsions containing fluorocarbons
WO2010065059A1 (en) * 2008-11-25 2010-06-10 Oxygen Biotherapeutics, Inc. Perfluorocarbon gel formulations

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE881267A (en) * 1980-01-18 1980-05-16 Stein Karl N METHOD FOR THE TREATMENT OF SKIN BURNS IN MAMMALS
WO1981000002A1 (en) * 1979-06-25 1981-01-08 Suntech Use of perfluorocarbon as burn treatment
EP0112658A2 (en) * 1982-11-26 1984-07-04 Children's Hospital Medical Center Extraocular device for treating the eye

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2743842C2 (en) * 1976-10-01 1982-07-01 Matsushita Electric Industrial Co., Ltd., Kadoma, Osaka Solid electrolytic capacitor and process for its manufacture

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1981000002A1 (en) * 1979-06-25 1981-01-08 Suntech Use of perfluorocarbon as burn treatment
BE881267A (en) * 1980-01-18 1980-05-16 Stein Karl N METHOD FOR THE TREATMENT OF SKIN BURNS IN MAMMALS
EP0112658A2 (en) * 1982-11-26 1984-07-04 Children's Hospital Medical Center Extraocular device for treating the eye

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO8900848A1 *

Also Published As

Publication number Publication date
AU2807689A (en) 1989-03-01
WO1989000848A1 (en) 1989-02-09
EP0324802A4 (en) 1991-07-24
JPH01503146A (en) 1989-10-26

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