CA1222453A - Enzyme ointment - Google Patents
Enzyme ointmentInfo
- Publication number
- CA1222453A CA1222453A CA000445785A CA445785A CA1222453A CA 1222453 A CA1222453 A CA 1222453A CA 000445785 A CA000445785 A CA 000445785A CA 445785 A CA445785 A CA 445785A CA 1222453 A CA1222453 A CA 1222453A
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- Prior art keywords
- ointment
- emollient
- penetrating
- skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- A61K38/166—Streptokinase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4826—Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A topical ointment for skin surface wounds comprising wound-healing amounts of papain, bromelain, trypsin, chymotrypsin, pancreatin, lipase, amylase, aloe extract and an organic astringent agent formulated in a carrier mixture of penetrating and non penetrating emollient oils and a polyhydric alcohol emollient. The ointment reduces inflammation at the site of skin-surface wounds and acts to enhance the normal anti-inflammatory activities of the body.
A topical ointment for skin surface wounds comprising wound-healing amounts of papain, bromelain, trypsin, chymotrypsin, pancreatin, lipase, amylase, aloe extract and an organic astringent agent formulated in a carrier mixture of penetrating and non penetrating emollient oils and a polyhydric alcohol emollient. The ointment reduces inflammation at the site of skin-surface wounds and acts to enhance the normal anti-inflammatory activities of the body.
Description
ENZYME OINTMENT
BACKGROUND OF THE INVENTION
In~ury to body tissues is immediately followed by acute local reaction characterized largely by a variety of vascular changes at the site of the inJury. These changes include the outpouring of plasma fluids, proteins, and white 6 blood cells, known collectively as exudate. This inflammatory response to inJury is virtually identical regar~less of the site of trauma in the body. See, Robbins & Angell, Basic B
g Pathology 32 (2nd ed. 1976) 1 Certain prostaglandins, i.e. P5E, and thromboxanes 11 are thought to be synthesized at the trauma site and are 12 believed to be important mediators of the vascular adjustments 13 to be made in the inflammatory response of the body. See, 14 Rob~ins ~ An~,ell, Basic Pathology 38 (2nd ed. 1976). As the prostaglandin level increases, a series of changes occur at 16 the trauma site. Platelet aggregation occurs, which is 17 followed by the release Or clotting factors such as fibrin and 18 thrombin. There is a release of en~yme blocking factors which 19 prevent fibrin dissolution and further strengthen the response. Smooth muscle contraction then leads to decreased 21 vascular permeability, trapping excess fluid and necrotic 22 debri~ within this fortified network. The body eventually 23 completely lsolates the damaged area and the physical symptoms
BACKGROUND OF THE INVENTION
In~ury to body tissues is immediately followed by acute local reaction characterized largely by a variety of vascular changes at the site of the inJury. These changes include the outpouring of plasma fluids, proteins, and white 6 blood cells, known collectively as exudate. This inflammatory response to inJury is virtually identical regar~less of the site of trauma in the body. See, Robbins & Angell, Basic B
g Pathology 32 (2nd ed. 1976) 1 Certain prostaglandins, i.e. P5E, and thromboxanes 11 are thought to be synthesized at the trauma site and are 12 believed to be important mediators of the vascular adjustments 13 to be made in the inflammatory response of the body. See, 14 Rob~ins ~ An~,ell, Basic Pathology 38 (2nd ed. 1976). As the prostaglandin level increases, a series of changes occur at 16 the trauma site. Platelet aggregation occurs, which is 17 followed by the release Or clotting factors such as fibrin and 18 thrombin. There is a release of en~yme blocking factors which 19 prevent fibrin dissolution and further strengthen the response. Smooth muscle contraction then leads to decreased 21 vascular permeability, trapping excess fluid and necrotic 22 debri~ within this fortified network. The body eventually 23 completely lsolates the damaged area and the physical symptoms
2~ of edema, heat, erythema and pain become prevalent.
Thus, once sub~ected to trauma the body tends to 26 isolate and "wall-in" at the trauma site exudate 7 necrotic 27 debris, which is primarily protein in nature, and any 28 entrapped bacteria ard viruses, ~hich are primarily composed 29 Of protein and lipids. Particularly in She case of acute trauma, which i prevalent with respect to ~kin-~urface -a~
:~2~ 3 in~uries, the accumulation of these substances may be substantial if there is a significant loss of tissue. When
Thus, once sub~ected to trauma the body tends to 26 isolate and "wall-in" at the trauma site exudate 7 necrotic 27 debris, which is primarily protein in nature, and any 28 entrapped bacteria ard viruses, ~hich are primarily composed 29 Of protein and lipids. Particularly in She case of acute trauma, which i prevalent with respect to ~kin-~urface -a~
:~2~ 3 in~uries, the accumulation of these substances may be substantial if there is a significant loss of tissue. When
3 this situation occurs, the system is overwhelmed thereby retarding tissue repair.
Plasma proteins such as plasminogen and fibrinolysin 6 and the hepatic anticoagulent heparin are usually able to 7 control inflammation during normal homeostasis. When the 8 ~ystem is overwhelmed, however, as in the case of acute g trauma, additional aid is needed by the body to control and alleviate the symptoms of inflamm~tion, since restoration of 11 the damaged tissue cannot be initiated until inflammation is 12 reduce~.
13 The accumulation of white blood cells as part of the 14 exudate, principally neutrophils and macrophaees, is part of the body' 9 response to alleviate the symptoms of inflammation.
16 For instance, both neutrophils and macrophaees contain an 17 abundance of lysosomes containing proteolytic enzymes which 18 are capable of digesting protein matter and bacteria.
19 Moreover, the lysosomes of macrophages are known to contain large qu~ntities of lipases, which are capable of digeqtine 21 the thick lipid membranes of certain bacteria. See Guyton, 22 Textbook Or Medical Physiology 70 (5th ed. 1976).
23 These defenses, however, are often inadequate to 24 effectuate rapid healing, particularly in acute skin-surface 25 ~ wounds, when there are exce~slve quantities of protein~ and 26 liquids "walled off" from the rest of the body. Thus, while 27 the human body does in fact utilize proteolytic and other 28 enzymes to effectuate an anti-inflammatory respon~e, the full 29 potential o~ these and other enæymes in con~unction wlth other 3~ sub~tances ~or the alleviation o~ skin-surface wound :~222'~;3 1 inflammation in a topical application has not heretofore been 2 realized.
3 It is therefore an ob~ect of the present invention
Plasma proteins such as plasminogen and fibrinolysin 6 and the hepatic anticoagulent heparin are usually able to 7 control inflammation during normal homeostasis. When the 8 ~ystem is overwhelmed, however, as in the case of acute g trauma, additional aid is needed by the body to control and alleviate the symptoms of inflamm~tion, since restoration of 11 the damaged tissue cannot be initiated until inflammation is 12 reduce~.
13 The accumulation of white blood cells as part of the 14 exudate, principally neutrophils and macrophaees, is part of the body' 9 response to alleviate the symptoms of inflammation.
16 For instance, both neutrophils and macrophaees contain an 17 abundance of lysosomes containing proteolytic enzymes which 18 are capable of digesting protein matter and bacteria.
19 Moreover, the lysosomes of macrophages are known to contain large qu~ntities of lipases, which are capable of digeqtine 21 the thick lipid membranes of certain bacteria. See Guyton, 22 Textbook Or Medical Physiology 70 (5th ed. 1976).
23 These defenses, however, are often inadequate to 24 effectuate rapid healing, particularly in acute skin-surface 25 ~ wounds, when there are exce~slve quantities of protein~ and 26 liquids "walled off" from the rest of the body. Thus, while 27 the human body does in fact utilize proteolytic and other 28 enzymes to effectuate an anti-inflammatory respon~e, the full 29 potential o~ these and other enæymes in con~unction wlth other 3~ sub~tances ~or the alleviation o~ skin-surface wound :~222'~;3 1 inflammation in a topical application has not heretofore been 2 realized.
3 It is therefore an ob~ect of the present invention
4 to provide co~positions whereby effective wound-healin~
amounts of proteolytic and other enzymes, in conjunction with 6 other wound-healing ~ubstances, may be topically applied to a 7 skin-surface wound.
8 It is another object of the present invention to 9 enhance the normal anti-inflammatory activity of proteoly~ic enzymes.
11 It is yet another object of the present invention to 12 provide substances in a composition which act synergistically 13 to reduce swelling and pain at the site of skin-surface trauma 14 and degeneration.
Other ob~ects and advantages of the invention will 16 become apparent upon consideration of the accompanying 17 disclosure.
18 BRIEF DESCRIPTION OF TH~ INVENTION
19 The compositions of the present invention are ointments comprising a carrier mixture of penetrating and 21 non-penetrating emollient oils and a polyhydric alcohol 22 emollient; the proteolytic and other enzymes papain, 23 bromelain, trypsin, chymotrypsin, pancreatin, lipase and 24 a~ylase; aloe extract; and an organic astringent agent. The carrier mixture, enzymes, aloe extract and the organic 26 astringent agent function synergistically so as to provide an 27 effective wound-healing topical ointment.
The general pathology o~ wound~processes involved in overt skin-~urface degeneration (ulcer~) and traumatic wounds ~222'~;i3 l (cuts, bruises, etc.) has been discussed herein~bove, alon~
~ with the action of certain enzymes in the healing process.
3 The natural limitations of the human body in the 4 healing process, however, creates a need to expedite healing thereby decreasing the discomfort experienced by the afflicted 6 1ndividual.
7 In this regard, the compositions Or the present 8 invention are formulated so as to deliver w3und-healing g amounts of proteolytic enzymes to the scarred or otherwise traumatized site, in conjunction with reparative qua~tities of ll an aloe extract, an organic astringent agent, lipase, amylase, 12 and carrier emollient oils. The phrase "wound-healing" as 13 used herein is intended to refer to the process of tissue 14 repair and to the reAuction of symptoms of inflam~ation present due to the body' 9 response to the cellular disruption 16 of skin-surface mammalian tissue which is either traumatic, as 17 in the case of a burn or cut, or on the other hand, 18 representative of a degenerative proce~s, such as an ulcer.
19 As an essential ingredient, the compositions of the present invention include a plurality of proteolytic enzymes, 21 which generally function to hydrolize or to lyse proteins into 22 their component amino acids, thereby providing these essential 23 amino acid3 in nutritionally adequate amounts. Fibrolytic, 24 proteolytic enzymes po3sess the added capacity to lyse or digest fibrin clot~ at wound sites. This action tends to 26 reAtore the free ~low of blood through the circulatory system 27 thereby accelerating the healing process at wound ~ites and 28 minimizing the development of scar ti~sue.
29 Moreover, proteolytic enzymes are believed to aid in the prevention of blood platelet aggregation, to increa~e ~2~2~3 l tissue permeabllity and to enhance the natural proteolytic and 2 fibrlnolytic activity of the blood. Proteolytic enzymes ha~e 3 also been implicated as inhibitors of the en2yme~blocking 4 factors previously discussed. In effect, these anti-inflammatory agenSs are prostaglandin inhibitors. Thus 7 the 6 compositions of the invention will comprise one or more of the 7 proteolytic enzymes streptokinase, urokinase, trypsin, 8 chymotryp~in, papain, bromelain and pancreatin. In a g preferred embodiment, all Or these enzymes except streptokinase and urokinase are contained in the composition.
ll Trypsin and chymotrypsin have been demonstrated to 12 be successful in the dissolution of the clotting factor 13 fibrin, necrotic tis~ue and proteinaceous exudates. When 14 applied topically to post-thrombotic leg ulcers, they have shown remarkable success in acceleratine the healing process.
16 See, C.ordon, The Use of Topical Proteolytic Enzy~es in the 17 Treatment of Post-thrombotic Leg Ulcers, Brit. J. Clin. Prac., 18 29, 143 (1975). Moreover, trypsin and chymotrypsin are l9 thought to have a favurable influence on the inflammatory process in thromophlebitis. It is expected that streptokinase 21 and urokinase would exhibit similar actions when applied 22 topically in an active form, and may be used in addition to, 23 or as replacements for, the trypsins.
24 While trypsin and chymotrypsin are often used in 25 1! combination for the prevention and treatment of inflammati~n 26 from in~ury, each may be used in the formulation of the 27 pre~ent invention withouS the other. Preferably, trypsin will 28 make up about .025-2.5~ by weight and chymotrypsin about 29 .001-1~ by ~eight of the compositions of the pre~ent invention and most preferablyi about .05-1% and .002~ , respectively.
l Papain has been reported to achieve excellent 2 results in promoting the healine of wounds. See, Hwang & Ivy, 3 A Review of the Literature on the Potential Therapeutic 4 Significance of Papain, Annals N.Y. Acad. Science, 54, 151 (1951-52). Indeed, papain has demonstrated clinical efficacy 6 as a local agent to debride or solubilize collections of 7 proteinaceous materials in an anti-inrlammatory role. See, 8 Emele et al., The Analgesic-Anti-Inflammatory activity of 9 Papain, Arch. int. Phar~acodyn., 159, 126 (1966). Moreover, papain acts not only upon ~ibrinogen, the precursor of fibrin, ll and other proteins, but alqo to destroy certain bacteria and 12 viruses which may be contained in the wound. See, Hwang &
13 Ivy, A Review of the Literature on the Potential Therapeutic 14 Significance of Papain, Annals N.Y. Acad. ~Scl_nce, 54, 161 (1951-52).
16 Papain is considered to be clinically efficacious in a topical application in removing clotted blood, purulent 18 exudate and necrotic ti3sue from skin-surface wounds and l9 ulcers. Preferably, papain will make up about .05-5% by weight of the compositions according to the invention and most 21 preferably, about .1-2%.
It has been proposed that the proteolytic thiol-enzyme ("SH-enzyme") bromelain acts to selectively inhibit the biosynthesi~ of proinflammatory prostaglandins, Quch as the platelet-aggregating thromboxane~. The use of bromelain is 26 indicated since the endogenous proteases such as circulatin~
27 plasmin, trypsin, chymotrypsin, and lipa~es are inhibited by 28 trauma or exposure to excessive str0s~. Bromelain also acts on fibrinogen and fibrin to yield products ~imilar to those formed by plasmin and which stimulate the biosynthesis of l anti-inflamatory prostaglandins such as PGI2. Indeed, it has 2 been reported that the efficacious results achieved in 3 revers~ng the inflammatory state may be a direct action of 4 bromelain on the proteins, including fibrin, deposited at the trauma site. See, S.J. Taussig, ~ed. Hypth., 6, 99 (1930), and 6 J.M. Miller et al. Exptl Med. Surg., 22, 277 (1964).
7 Preferably, bromelain will make up about .05-5~ by 8 weight o~ the total enzyme component of the composition 9 according to the invention and most preferably, abo~lt .1~2~.
The compositions of the invention will also ll preferably incorporate an amount of pancreatin, or of the 12 individual primary enzymes incorporated therein, or of 13 mixtures of the individual enzymes with pancreatin.
14 Pancreatin primarily contains amylase, protease and lipase;
digestive enzymes which act to break down dietary starch, 16 protein and fat, respectively. Since pancreatic deficiency or 17 overload is implicated in many situations involving wounds, it 18 is believed that a supplemental amount o~ pancreatin is a l9 beneficial adjunct to the administration of the fibrinolytic and anti-inflammatory enzymes. Pancreatin aids in the 21 restoration of normal digestive processes, including the 22 proper metabolism of fats, which is necessary for the achievement of e~fective plasma levels of anticlotting and antiinflammatory prostaglandins. Pancreatin and/or its component enzymes preferably compri e up to about .1-10% by 26 weight o~ the compositions of the present invention, most preferably about .2-2%.
28 The compositions of the present invention will also preferably include topically wound-clean~ing amounts of pancreatic digestive enzymes such aq lipa es and~or amylases, --7~
~222~3 1 which are thought to effect the fats and carbohydrates 2 contained in the structure of bacteria and viruses. For 3 instance, many types of viruses possess an outer cell envelope 4 composed of protein, lipid and carbohydrate constituents.
Amylase and/or lipase, in conjunction with the proteolytic 6 enzymes of the present invention, are thought to act 7 synergistically to degrade the cell envelope and protein an~
8 lipid components of the virus particle so as to inactivate the 9 pathenogicity of viruses contained in or entering the wound.
Similarly, the cell wall and me.~brane of many 11 strains of bacteria are rich in proteins, carbohydrates and 12 fat~. Consequently, a topical application of the compositions 13 of the invention are thought to act on the cell wall and 14 membrane of the bacterial cell leadin~ to the lysing of the microorganism with a consequent loss of virulence. In this 16 manner, wound-healing is aided by the control of infectious 17 microorganisms.
18 Preferably, the pancreatic digestive en~yme~ such as 19 lipase and amylase will each make up about .01-5% of the compositionC of the present invention and most preferably, 21 about .05~
22 In order to enhance the reparative qualities of the ~ hereinbefore discussed enzymes, the compositions according to 24 the invention may also include an aloe extract and an organic astringent agent.
26 The aloe extract, which iQ preferably incorporated 27 as an aloe concentrate, e.g. aloe vera or aloe perryi concentrate, is thought to promote healing and has been applled aY a soothing cream to skin-surface wound~, burns and ~car ti~sue. In addition to being a rapid penetrator o~ the ~2~5~3 1 ~ariou~ ~kin layer~, the aloe extract contains enzymes which ~ promote the removal of dead skin ~hile ~timulating the normal 3 ~rowth of livin~ ti~ue. As defined herein, the term "aloe 4 extract" refers to the inspissated Juice of the aloe plant as well as to its dried concentrates which contain aloe-emodin, aloin or other active anthraquinone principles.
7 The preferable organic astringent agent is witch ~ hazel, a herb ~ubstance which ha~ demonstrated effectiveness 9 as an astringent for the treatment Or itchin~, skin irritations and burns., This compound acts to inhibit the 11 pathological transcapillary movement of plasma protein thereby 12 reducins inflammation, edema and exudation. Witch hazel has 13 been u~ed in an anti~eptic capacity for the healing of wounds 14 and for cleansing the skin surface.
The composition~ of the pre~ent invention may also 16 include one or more of a mixture of carrier emollients of a 17 penetrating emollient oil, a non-penetrating emollient oil and 18 a polyhydric alcohol emollient.
Preferably, the penetrating emollient oil will be ethoxylated lanolin. In addition to its skin softening 21 propert~es, lanolin is known to be er~ect~ve as a mois~urizer 22 and lubricant. The ~ubstance penetrates into the skin sur~ace quickly and is quite beneficial when applied to skin-surface wound~ ~ince lt acts to prevent a dre~sing ~rom sticking to the wound~ Thi~ ef~ecti~e penetra~or al~o acts to repleni~h 26 Yaluable lipids in the wound area. Other characteristics of 27 lanolin are ~i~clo~ed in U.S. Patent No. 2,47~,820 U~eful compound~ of thls type are formed by the conden~aticn o~ about 10-80 moles of ethylene oxlde per ~ole o~ lanolin or ~.~zz~53 l ~ by the llnking of ~orbltol and lanolin w~th a polyoxyethylene 2 1l chain containing 10-80 mole~ Or ethylene oxlde.
3 Particularly useful compounds o~ this type are 4 commercially available from ICI Americas, Wilmington, Del. as Atla~ G-1790 (20 mole~ of ethylene oxide~mole of lanolin), ¦1 AtlaY~ G-14~1 (40 mole~ of ethylene oxide linking ~orbitol and 7 l~ lanolin) and Atlas~ C 1471 ~75 moles of ethylene oxide llnking 8 l ~orbitol and lanolin).
9 1I The preferred non-penetrating emollient oil is lO 1l petrolatum, which is known to aid in restoring the natural texture Or the ~kin ~urrace. Unlike ethoxylated lanolin, 12 I petrolatum i~ a non-penetrating moisturizer and lubricant for 13 ii the ~kin surface and a~ such, act~ to aid in the topical 14 ll act~on Or the compo~ition of the present invention.
15 I The preferred polyhydric alcohol emollient is 6 ll glycerin. Its main utility is in moi~turizing the ~kin and !I providing a medium solvent. It is also reported to pos~e~
¦I therapeutic uses ~uch a~ itq application to reduce corneal l9 ll sdema. See, Remington's Pharmaceutical Sciences, A. O~ol ed, 2 1i Mack Pub., Boston, Ma~s. (16th ed. 1980) at page 1255.
21 ll The weight percent of the carrier emollient~ i 1 sub~tantially greater than that o~ any Or the other components 23 of the invention. Preferably, the carrier emollient~ compri3e about 85-99~ o~ the total weight Or the compo~1tion~ of the presen~ invention and mo~t preferably, about 93-97~.
~7 ¦ The compo~itions Or the present in~ention may alYo I include one or more antibaeterial pre~ervatiYes, pre~erably 2~ 1 from the C1-C4 lower alkyl benzoates such as ~ethyl and propyl paraben, each with a total weight percent in the compo~ition~
Or about .025-1.5~; preferably.
... , . _ .. .. . __ _. ,. _ . . _ . _ ... _ . _ . . _ . . . . . . . .. . . .. . .
~L222~;3 l I The total weight percent Or the components of the 2 ,I compo~itions Or the pre~ent invention may be varied over a 3 1! wide range. For example, the weight percent of all of the 4 enzymes in the compositionq is preferably ~bout .2-20% and of S ~ust the proteolytic enzymes, about .2-15~. The weight 6 Ij percent of aloe extract preferably ranges rrom about .05_3 7 and the weight percent of the organic astringent agent 8 preferably rangeq from about .o6-3~.
9 Thus, ln a preferred embodiment of the composition according to the invention, the respecSive weight percents 11 I would be as follows: enzymes, .2-20%; aloe extract, 0.02-10%, 12 or preferably .05-3~; organic aqtringent agent, .025-ô~, or 13 . pre~erably .06-3~; petrolatum, 40-80%; ethoxylated lanolin, 14 , 5_30~; glycerine 5-30~, and preservative~ .05-3%.
lS ,I Preferably, the compo~itions of the pre~ent 16 . invention will be formulated ~uch that the total enzyme 17 ll component will comprise, by weight, papain, about 15-40%;
l 1, trypsin, about 5-15S; chymotrypsin, about .2-.6%; bromel~in, about 10-30~; pancreatin, about 30~50%; lipase, about 2-8~;
l and amylase, about 2-8~.
¦l The wound-healing, reparative quality of the ointment may be erfectuated by means of the method according ~j to the pre~ent invention. The method compr-i~es the topical ¦ adminiqtration of an effective amount of the hereinabove !l di~cussed composition~ to traumatic or degenerative skin-26 il I' surface wounds.
27 ', ij The ointmeDts are typ~cally prepared by ~irst mixing 2~ ll Il the carrier emollients. A 3econd homogeneou~ mixture of en~ymes and aloe extract i~ then slowly incorporated into a ¦ 3mall a~ount vf the carrier emollient mixture. The re~ultant ~2~2~53 !l paste i~ then added to the remainder o~ the carrier emollient Il mixture while mixing in a mixer. A second homogeneous paste, 3 ll composed of the organic astringent agent and a ~mall quantity 4 o~ the carrier emollient mixture ls then added to the mixer
amounts of proteolytic and other enzymes, in conjunction with 6 other wound-healing ~ubstances, may be topically applied to a 7 skin-surface wound.
8 It is another object of the present invention to 9 enhance the normal anti-inflammatory activity of proteoly~ic enzymes.
11 It is yet another object of the present invention to 12 provide substances in a composition which act synergistically 13 to reduce swelling and pain at the site of skin-surface trauma 14 and degeneration.
Other ob~ects and advantages of the invention will 16 become apparent upon consideration of the accompanying 17 disclosure.
18 BRIEF DESCRIPTION OF TH~ INVENTION
19 The compositions of the present invention are ointments comprising a carrier mixture of penetrating and 21 non-penetrating emollient oils and a polyhydric alcohol 22 emollient; the proteolytic and other enzymes papain, 23 bromelain, trypsin, chymotrypsin, pancreatin, lipase and 24 a~ylase; aloe extract; and an organic astringent agent. The carrier mixture, enzymes, aloe extract and the organic 26 astringent agent function synergistically so as to provide an 27 effective wound-healing topical ointment.
The general pathology o~ wound~processes involved in overt skin-~urface degeneration (ulcer~) and traumatic wounds ~222'~;i3 l (cuts, bruises, etc.) has been discussed herein~bove, alon~
~ with the action of certain enzymes in the healing process.
3 The natural limitations of the human body in the 4 healing process, however, creates a need to expedite healing thereby decreasing the discomfort experienced by the afflicted 6 1ndividual.
7 In this regard, the compositions Or the present 8 invention are formulated so as to deliver w3und-healing g amounts of proteolytic enzymes to the scarred or otherwise traumatized site, in conjunction with reparative qua~tities of ll an aloe extract, an organic astringent agent, lipase, amylase, 12 and carrier emollient oils. The phrase "wound-healing" as 13 used herein is intended to refer to the process of tissue 14 repair and to the reAuction of symptoms of inflam~ation present due to the body' 9 response to the cellular disruption 16 of skin-surface mammalian tissue which is either traumatic, as 17 in the case of a burn or cut, or on the other hand, 18 representative of a degenerative proce~s, such as an ulcer.
19 As an essential ingredient, the compositions of the present invention include a plurality of proteolytic enzymes, 21 which generally function to hydrolize or to lyse proteins into 22 their component amino acids, thereby providing these essential 23 amino acid3 in nutritionally adequate amounts. Fibrolytic, 24 proteolytic enzymes po3sess the added capacity to lyse or digest fibrin clot~ at wound sites. This action tends to 26 reAtore the free ~low of blood through the circulatory system 27 thereby accelerating the healing process at wound ~ites and 28 minimizing the development of scar ti~sue.
29 Moreover, proteolytic enzymes are believed to aid in the prevention of blood platelet aggregation, to increa~e ~2~2~3 l tissue permeabllity and to enhance the natural proteolytic and 2 fibrlnolytic activity of the blood. Proteolytic enzymes ha~e 3 also been implicated as inhibitors of the en2yme~blocking 4 factors previously discussed. In effect, these anti-inflammatory agenSs are prostaglandin inhibitors. Thus 7 the 6 compositions of the invention will comprise one or more of the 7 proteolytic enzymes streptokinase, urokinase, trypsin, 8 chymotryp~in, papain, bromelain and pancreatin. In a g preferred embodiment, all Or these enzymes except streptokinase and urokinase are contained in the composition.
ll Trypsin and chymotrypsin have been demonstrated to 12 be successful in the dissolution of the clotting factor 13 fibrin, necrotic tis~ue and proteinaceous exudates. When 14 applied topically to post-thrombotic leg ulcers, they have shown remarkable success in acceleratine the healing process.
16 See, C.ordon, The Use of Topical Proteolytic Enzy~es in the 17 Treatment of Post-thrombotic Leg Ulcers, Brit. J. Clin. Prac., 18 29, 143 (1975). Moreover, trypsin and chymotrypsin are l9 thought to have a favurable influence on the inflammatory process in thromophlebitis. It is expected that streptokinase 21 and urokinase would exhibit similar actions when applied 22 topically in an active form, and may be used in addition to, 23 or as replacements for, the trypsins.
24 While trypsin and chymotrypsin are often used in 25 1! combination for the prevention and treatment of inflammati~n 26 from in~ury, each may be used in the formulation of the 27 pre~ent invention withouS the other. Preferably, trypsin will 28 make up about .025-2.5~ by weight and chymotrypsin about 29 .001-1~ by ~eight of the compositions of the pre~ent invention and most preferablyi about .05-1% and .002~ , respectively.
l Papain has been reported to achieve excellent 2 results in promoting the healine of wounds. See, Hwang & Ivy, 3 A Review of the Literature on the Potential Therapeutic 4 Significance of Papain, Annals N.Y. Acad. Science, 54, 151 (1951-52). Indeed, papain has demonstrated clinical efficacy 6 as a local agent to debride or solubilize collections of 7 proteinaceous materials in an anti-inrlammatory role. See, 8 Emele et al., The Analgesic-Anti-Inflammatory activity of 9 Papain, Arch. int. Phar~acodyn., 159, 126 (1966). Moreover, papain acts not only upon ~ibrinogen, the precursor of fibrin, ll and other proteins, but alqo to destroy certain bacteria and 12 viruses which may be contained in the wound. See, Hwang &
13 Ivy, A Review of the Literature on the Potential Therapeutic 14 Significance of Papain, Annals N.Y. Acad. ~Scl_nce, 54, 161 (1951-52).
16 Papain is considered to be clinically efficacious in a topical application in removing clotted blood, purulent 18 exudate and necrotic ti3sue from skin-surface wounds and l9 ulcers. Preferably, papain will make up about .05-5% by weight of the compositions according to the invention and most 21 preferably, about .1-2%.
It has been proposed that the proteolytic thiol-enzyme ("SH-enzyme") bromelain acts to selectively inhibit the biosynthesi~ of proinflammatory prostaglandins, Quch as the platelet-aggregating thromboxane~. The use of bromelain is 26 indicated since the endogenous proteases such as circulatin~
27 plasmin, trypsin, chymotrypsin, and lipa~es are inhibited by 28 trauma or exposure to excessive str0s~. Bromelain also acts on fibrinogen and fibrin to yield products ~imilar to those formed by plasmin and which stimulate the biosynthesis of l anti-inflamatory prostaglandins such as PGI2. Indeed, it has 2 been reported that the efficacious results achieved in 3 revers~ng the inflammatory state may be a direct action of 4 bromelain on the proteins, including fibrin, deposited at the trauma site. See, S.J. Taussig, ~ed. Hypth., 6, 99 (1930), and 6 J.M. Miller et al. Exptl Med. Surg., 22, 277 (1964).
7 Preferably, bromelain will make up about .05-5~ by 8 weight o~ the total enzyme component of the composition 9 according to the invention and most preferably, abo~lt .1~2~.
The compositions of the invention will also ll preferably incorporate an amount of pancreatin, or of the 12 individual primary enzymes incorporated therein, or of 13 mixtures of the individual enzymes with pancreatin.
14 Pancreatin primarily contains amylase, protease and lipase;
digestive enzymes which act to break down dietary starch, 16 protein and fat, respectively. Since pancreatic deficiency or 17 overload is implicated in many situations involving wounds, it 18 is believed that a supplemental amount o~ pancreatin is a l9 beneficial adjunct to the administration of the fibrinolytic and anti-inflammatory enzymes. Pancreatin aids in the 21 restoration of normal digestive processes, including the 22 proper metabolism of fats, which is necessary for the achievement of e~fective plasma levels of anticlotting and antiinflammatory prostaglandins. Pancreatin and/or its component enzymes preferably compri e up to about .1-10% by 26 weight o~ the compositions of the present invention, most preferably about .2-2%.
28 The compositions of the present invention will also preferably include topically wound-clean~ing amounts of pancreatic digestive enzymes such aq lipa es and~or amylases, --7~
~222~3 1 which are thought to effect the fats and carbohydrates 2 contained in the structure of bacteria and viruses. For 3 instance, many types of viruses possess an outer cell envelope 4 composed of protein, lipid and carbohydrate constituents.
Amylase and/or lipase, in conjunction with the proteolytic 6 enzymes of the present invention, are thought to act 7 synergistically to degrade the cell envelope and protein an~
8 lipid components of the virus particle so as to inactivate the 9 pathenogicity of viruses contained in or entering the wound.
Similarly, the cell wall and me.~brane of many 11 strains of bacteria are rich in proteins, carbohydrates and 12 fat~. Consequently, a topical application of the compositions 13 of the invention are thought to act on the cell wall and 14 membrane of the bacterial cell leadin~ to the lysing of the microorganism with a consequent loss of virulence. In this 16 manner, wound-healing is aided by the control of infectious 17 microorganisms.
18 Preferably, the pancreatic digestive en~yme~ such as 19 lipase and amylase will each make up about .01-5% of the compositionC of the present invention and most preferably, 21 about .05~
22 In order to enhance the reparative qualities of the ~ hereinbefore discussed enzymes, the compositions according to 24 the invention may also include an aloe extract and an organic astringent agent.
26 The aloe extract, which iQ preferably incorporated 27 as an aloe concentrate, e.g. aloe vera or aloe perryi concentrate, is thought to promote healing and has been applled aY a soothing cream to skin-surface wound~, burns and ~car ti~sue. In addition to being a rapid penetrator o~ the ~2~5~3 1 ~ariou~ ~kin layer~, the aloe extract contains enzymes which ~ promote the removal of dead skin ~hile ~timulating the normal 3 ~rowth of livin~ ti~ue. As defined herein, the term "aloe 4 extract" refers to the inspissated Juice of the aloe plant as well as to its dried concentrates which contain aloe-emodin, aloin or other active anthraquinone principles.
7 The preferable organic astringent agent is witch ~ hazel, a herb ~ubstance which ha~ demonstrated effectiveness 9 as an astringent for the treatment Or itchin~, skin irritations and burns., This compound acts to inhibit the 11 pathological transcapillary movement of plasma protein thereby 12 reducins inflammation, edema and exudation. Witch hazel has 13 been u~ed in an anti~eptic capacity for the healing of wounds 14 and for cleansing the skin surface.
The composition~ of the pre~ent invention may also 16 include one or more of a mixture of carrier emollients of a 17 penetrating emollient oil, a non-penetrating emollient oil and 18 a polyhydric alcohol emollient.
Preferably, the penetrating emollient oil will be ethoxylated lanolin. In addition to its skin softening 21 propert~es, lanolin is known to be er~ect~ve as a mois~urizer 22 and lubricant. The ~ubstance penetrates into the skin sur~ace quickly and is quite beneficial when applied to skin-surface wound~ ~ince lt acts to prevent a dre~sing ~rom sticking to the wound~ Thi~ ef~ecti~e penetra~or al~o acts to repleni~h 26 Yaluable lipids in the wound area. Other characteristics of 27 lanolin are ~i~clo~ed in U.S. Patent No. 2,47~,820 U~eful compound~ of thls type are formed by the conden~aticn o~ about 10-80 moles of ethylene oxlde per ~ole o~ lanolin or ~.~zz~53 l ~ by the llnking of ~orbltol and lanolin w~th a polyoxyethylene 2 1l chain containing 10-80 mole~ Or ethylene oxlde.
3 Particularly useful compounds o~ this type are 4 commercially available from ICI Americas, Wilmington, Del. as Atla~ G-1790 (20 mole~ of ethylene oxide~mole of lanolin), ¦1 AtlaY~ G-14~1 (40 mole~ of ethylene oxide linking ~orbitol and 7 l~ lanolin) and Atlas~ C 1471 ~75 moles of ethylene oxide llnking 8 l ~orbitol and lanolin).
9 1I The preferred non-penetrating emollient oil is lO 1l petrolatum, which is known to aid in restoring the natural texture Or the ~kin ~urrace. Unlike ethoxylated lanolin, 12 I petrolatum i~ a non-penetrating moisturizer and lubricant for 13 ii the ~kin surface and a~ such, act~ to aid in the topical 14 ll act~on Or the compo~ition of the present invention.
15 I The preferred polyhydric alcohol emollient is 6 ll glycerin. Its main utility is in moi~turizing the ~kin and !I providing a medium solvent. It is also reported to pos~e~
¦I therapeutic uses ~uch a~ itq application to reduce corneal l9 ll sdema. See, Remington's Pharmaceutical Sciences, A. O~ol ed, 2 1i Mack Pub., Boston, Ma~s. (16th ed. 1980) at page 1255.
21 ll The weight percent of the carrier emollient~ i 1 sub~tantially greater than that o~ any Or the other components 23 of the invention. Preferably, the carrier emollient~ compri3e about 85-99~ o~ the total weight Or the compo~1tion~ of the presen~ invention and mo~t preferably, about 93-97~.
~7 ¦ The compo~itions Or the present in~ention may alYo I include one or more antibaeterial pre~ervatiYes, pre~erably 2~ 1 from the C1-C4 lower alkyl benzoates such as ~ethyl and propyl paraben, each with a total weight percent in the compo~ition~
Or about .025-1.5~; preferably.
... , . _ .. .. . __ _. ,. _ . . _ . _ ... _ . _ . . _ . . . . . . . .. . . .. . .
~L222~;3 l I The total weight percent Or the components of the 2 ,I compo~itions Or the pre~ent invention may be varied over a 3 1! wide range. For example, the weight percent of all of the 4 enzymes in the compositionq is preferably ~bout .2-20% and of S ~ust the proteolytic enzymes, about .2-15~. The weight 6 Ij percent of aloe extract preferably ranges rrom about .05_3 7 and the weight percent of the organic astringent agent 8 preferably rangeq from about .o6-3~.
9 Thus, ln a preferred embodiment of the composition according to the invention, the respecSive weight percents 11 I would be as follows: enzymes, .2-20%; aloe extract, 0.02-10%, 12 or preferably .05-3~; organic aqtringent agent, .025-ô~, or 13 . pre~erably .06-3~; petrolatum, 40-80%; ethoxylated lanolin, 14 , 5_30~; glycerine 5-30~, and preservative~ .05-3%.
lS ,I Preferably, the compo~itions of the pre~ent 16 . invention will be formulated ~uch that the total enzyme 17 ll component will comprise, by weight, papain, about 15-40%;
l 1, trypsin, about 5-15S; chymotrypsin, about .2-.6%; bromel~in, about 10-30~; pancreatin, about 30~50%; lipase, about 2-8~;
l and amylase, about 2-8~.
¦l The wound-healing, reparative quality of the ointment may be erfectuated by means of the method according ~j to the pre~ent invention. The method compr-i~es the topical ¦ adminiqtration of an effective amount of the hereinabove !l di~cussed composition~ to traumatic or degenerative skin-26 il I' surface wounds.
27 ', ij The ointmeDts are typ~cally prepared by ~irst mixing 2~ ll Il the carrier emollients. A 3econd homogeneou~ mixture of en~ymes and aloe extract i~ then slowly incorporated into a ¦ 3mall a~ount vf the carrier emollient mixture. The re~ultant ~2~2~53 !l paste i~ then added to the remainder o~ the carrier emollient Il mixture while mixing in a mixer. A second homogeneous paste, 3 ll composed of the organic astringent agent and a ~mall quantity 4 o~ the carrier emollient mixture ls then added to the mixer
5 and mixing o~ all the component~ is continued until the
6 I compo3it~0n begins to solidify. At this time~ the compo~ition
7 ll ls poured into a tube filling apparatus, pre~sure is applied
8 ll and the ointment ls tubed.
9 !I The invention will be ~urther described by reference lO I to the following detailed example.
1 I! EXAMPLE - ENZYME OINTMENT
12 ~1 A melt o~ 15,162 g of petrolatum, 4,364 g of 13 1 ethoxylated lanolin and 3,50g g of glycerin was prepared in a 14 I stainless steel container. Small amounts of a ~econd l5 i homogeneous mixture of 252 g o~ pancreatin, 153 g papain, 113 16 ll g of bro~elain, 25 g of lipase, 25 g of amylase, 60 g of 1 j tryp~in, 2.~ ~ of chymotrypsin and 42 g of aloe vera powder 8 ll extract ~ere added to small quantities of the melt in a 2 Il gallon ~tainless steel container. The resultant paste was 2 1l added to a larger quantity of the melt while mixing untll l 1I homogeneous in a "J.H. Day~ mixer.
Il A second paste wa~ made of 84 g of witch hazel 23 1 extract and a small amount of melt. ~hen the paste ~a~
I homogeneous, lt was added to the fir3t paste with mixing.
25 ~ When the homogeneous mixture began to 901idify, it wa~ poured i, ~nto a "Colton~ tube ~iiling machine and one ounce tubes were illed under 30 lbs. pres~ure.
The o~ntment of this inv~ntion has been u~ed in the 29 treatment of ~uperflcial wounds and bru~es and haR been ¦ reported as e~fectlve ~or such applications in providing I
122Z~ 3 1 Isymptomatic relie~. The recommended mode of application ~ to 2 ' apply a thin layer of the oint~ent to the afflicted area and 3 optionally cover ~ith a sterlle gauze dres~ing.
Q ~q a re~ult of the present invention, a novel ointment for skin-3urf`ace wound-heallng has been provided.
6 ¦ Although a preferred embodiment of the prlnciple~ of this 7 ¦, invention ha~ been deqcribed in detail herein, it should be 8 ll realized that the 3ame are not limited to the particular g l' embodiments described and that modification~ thereof` are
1 I! EXAMPLE - ENZYME OINTMENT
12 ~1 A melt o~ 15,162 g of petrolatum, 4,364 g of 13 1 ethoxylated lanolin and 3,50g g of glycerin was prepared in a 14 I stainless steel container. Small amounts of a ~econd l5 i homogeneous mixture of 252 g o~ pancreatin, 153 g papain, 113 16 ll g of bro~elain, 25 g of lipase, 25 g of amylase, 60 g of 1 j tryp~in, 2.~ ~ of chymotrypsin and 42 g of aloe vera powder 8 ll extract ~ere added to small quantities of the melt in a 2 Il gallon ~tainless steel container. The resultant paste was 2 1l added to a larger quantity of the melt while mixing untll l 1I homogeneous in a "J.H. Day~ mixer.
Il A second paste wa~ made of 84 g of witch hazel 23 1 extract and a small amount of melt. ~hen the paste ~a~
I homogeneous, lt was added to the fir3t paste with mixing.
25 ~ When the homogeneous mixture began to 901idify, it wa~ poured i, ~nto a "Colton~ tube ~iiling machine and one ounce tubes were illed under 30 lbs. pres~ure.
The o~ntment of this inv~ntion has been u~ed in the 29 treatment of ~uperflcial wounds and bru~es and haR been ¦ reported as e~fectlve ~or such applications in providing I
122Z~ 3 1 Isymptomatic relie~. The recommended mode of application ~ to 2 ' apply a thin layer of the oint~ent to the afflicted area and 3 optionally cover ~ith a sterlle gauze dres~ing.
Q ~q a re~ult of the present invention, a novel ointment for skin-3urf`ace wound-heallng has been provided.
6 ¦ Although a preferred embodiment of the prlnciple~ of this 7 ¦, invention ha~ been deqcribed in detail herein, it should be 8 ll realized that the 3ame are not limited to the particular g l' embodiments described and that modification~ thereof` are
10 I contemplated and can be made without departing from the broad plrit and 3cope of thiq invention a~ defined in the appended 12 Ij claims.
1 5 1 ' 7 !
18 1!
1 5 1 ' 7 !
18 1!
Claims (12)
1. A skin-surface, anti-inflammatory ointment comprising:
(a) a carrier emollient comprising a non-penetrating emollient oil, a penetrating emollient oil and a polyhydric alcohol emollient;
(b) a plurality of wound-healing proteolytic enzymes;
(c) an organic astringent agent; and (d) an aloe extract.
(a) a carrier emollient comprising a non-penetrating emollient oil, a penetrating emollient oil and a polyhydric alcohol emollient;
(b) a plurality of wound-healing proteolytic enzymes;
(c) an organic astringent agent; and (d) an aloe extract.
2. The ointment according to claim 1, wherein the non-penetrating emollient oil is petrolatum, the penetrating emollinent oil is an ethoxylated lanolin and the polyhydric alcohol emollient is glycerin.
3. The ointment according to claim 1, further comprising amylase and lipase.
4. The ointment according to claim 1, wherein the organic astringent agent is witch hazel.
5. The ointment according to claim 1, wherein the plurality of proteolytic enzymes comprises trypsin, chymotrypsin, pancreatin, papain and bromelain.
6. The ointment according to claim 1 wherein the plurality of enzymes comprises streptokinase, urokinase and mixtures thereof.
7. The ointment according to claim 5, wherein the plurality of proteolytic enzymes comprises about .2-15% by weight of the ointment.
8. The ointment according to claim 1, wherein the carrier emollient comprises about 93-97% by weight of the ointment.
9. A skin-surface, anti-inflammatory ointment comprising:
(a) about .1-2% papain;
(b) about .1-2% bromelain;
(c) about .2-2% pancreatin;
(d) about .05-1% trypsin;
(e) about .002-.1% chymotrypsin;
(f) about .05-1% lipase (g) about .05-1% amylase (h) about .05-3% aloe vera powder extract;
(i) about .06-3% witch hazel;
(j) about 40-80% petrolatum;
(k) about 5-30% ethoxylated lanolin; and (l) about 5-30% glycerin.
(a) about .1-2% papain;
(b) about .1-2% bromelain;
(c) about .2-2% pancreatin;
(d) about .05-1% trypsin;
(e) about .002-.1% chymotrypsin;
(f) about .05-1% lipase (g) about .05-1% amylase (h) about .05-3% aloe vera powder extract;
(i) about .06-3% witch hazel;
(j) about 40-80% petrolatum;
(k) about 5-30% ethoxylated lanolin; and (l) about 5-30% glycerin.
10. The ointment according to claim 9, further comprising about .05-3% of antibacterial preservative.
11. The ointment according to claim 3 wherein lipase comprises about .05-1% and amylase about .05-1% by weight of the ointment.
12. The ointment according to claim 1, wherein aloe extract comprises about .05-3% by weight of the ointment.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46002383A | 1983-01-21 | 1983-01-21 | |
| US460,023 | 1983-01-21 |
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| Publication Number | Publication Date |
|---|---|
| CA1222453A true CA1222453A (en) | 1987-06-02 |
Family
ID=23827108
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000445785A Expired CA1222453A (en) | 1983-01-21 | 1984-01-20 | Enzyme ointment |
Country Status (3)
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|---|---|
| EP (1) | EP0133438A1 (en) |
| CA (1) | CA1222453A (en) |
| WO (1) | WO1984002846A1 (en) |
Cited By (1)
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|---|---|---|---|---|
| CN106860860A (en) * | 2017-03-03 | 2017-06-20 | 钱安坤 | The new opplication of polyzyme tablets |
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| GB8821049D0 (en) * | 1988-09-08 | 1988-10-05 | Health Lab Service Board | Method & composition for treatment & prevention of viral infections |
| JPH02292226A (en) * | 1989-05-08 | 1990-12-03 | Shigemi Fujisaki | Agent for activating, preventing and treating disordered nerve cell |
| DE4130221C2 (en) * | 1991-09-11 | 1997-08-07 | Mucos Pharma Gmbh | Use of proteolytic enzymes for the manufacture of a medicament for the treatment of autoimmune diseases, in whose formation proteins with a C¶H¶2 domain are involved |
| GB9207288D0 (en) * | 1992-04-02 | 1992-05-13 | Unilever Plc | Cosmetic composition |
| GB9207280D0 (en) * | 1992-04-02 | 1992-05-13 | Unilever Plc | Skin care method and composition |
| DE4305460C2 (en) * | 1993-02-23 | 1997-09-04 | Albert Dr Scheller | Pharmaceutical or cosmetic preparation containing enzymes, process for their preparation and their use |
| EP0719133A1 (en) * | 1993-09-15 | 1996-07-03 | Unilever Plc | Skin care method and composition |
| GB9319104D0 (en) * | 1993-09-15 | 1993-11-03 | Unilever Plc | Skin care method & composition |
| US5543149A (en) * | 1995-03-01 | 1996-08-06 | Rubin; Stan M. | Treatment for insect bites |
| KR20010031170A (en) * | 1997-10-16 | 2001-04-16 | 주 데광 | a new powerful cosmetic or pharmaceutical composition |
| GR1003080B (en) | 1997-11-21 | 1999-02-25 | Preservation of enzymes in a concave bottle lid for use in cosmetic concoctions | |
| US6632429B1 (en) | 1999-12-17 | 2003-10-14 | Joan M. Fallon | Methods for treating pervasive development disorders |
| US20070053895A1 (en) | 2000-08-14 | 2007-03-08 | Fallon Joan M | Method of treating and diagnosing parkinsons disease and related dysautonomic disorders |
| US8030002B2 (en) | 2000-11-16 | 2011-10-04 | Curemark Llc | Methods for diagnosing pervasive development disorders, dysautonomia and other neurological conditions |
| WO2003066088A2 (en) * | 2002-02-06 | 2003-08-14 | Trommsdorff Gmbh & Co. Kg Arzneimittel | Protease screening and novel use of proteases |
| GB0423652D0 (en) * | 2004-10-25 | 2004-11-24 | Univ Coventry | Kit |
| US20080058282A1 (en) | 2005-08-30 | 2008-03-06 | Fallon Joan M | Use of lactulose in the treatment of autism |
| US8658163B2 (en) | 2008-03-13 | 2014-02-25 | Curemark Llc | Compositions and use thereof for treating symptoms of preeclampsia |
| US8084025B2 (en) | 2008-04-18 | 2011-12-27 | Curemark Llc | Method for the treatment of the symptoms of drug and alcohol addiction |
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| PL2318035T3 (en) | 2008-07-01 | 2019-10-31 | Curemark Llc | Methods and compositions for the treatment of symptoms of neurological and mental health disorders |
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| US20100092447A1 (en) | 2008-10-03 | 2010-04-15 | Fallon Joan M | Methods and compositions for the treatment of symptoms of prion diseases |
| JP5684725B2 (en) | 2009-01-06 | 2015-03-18 | キュレロン リミテッド ライアビリティ カンパニー | Compositions and methods for the treatment or prevention of S. aureus infections and compositions and methods for the eradication or reduction of S. aureus on the surface |
| AU2015252099B2 (en) * | 2009-01-06 | 2017-08-10 | Galenagen, Llc | Compositions and methods for the treatment or prevention of staphylococcus aureus infections and for the eradication or reduction of staphylococcus aureus on surfaces |
| CA2747703C (en) | 2009-01-06 | 2021-06-15 | Curemark Llc | Compositions and methods for the treatment or the prevention of infections by e. coli |
| US9056050B2 (en) | 2009-04-13 | 2015-06-16 | Curemark Llc | Enzyme delivery systems and methods of preparation and use |
| US9511125B2 (en) | 2009-10-21 | 2016-12-06 | Curemark Llc | Methods and compositions for the treatment of influenza |
| AU2012245287B2 (en) | 2011-04-21 | 2017-04-13 | Curemark, Llc | Compounds for the treatment of neuropsychiatric disorders |
| EP2809341B1 (en) * | 2012-02-02 | 2020-12-30 | Galenagen, LLC | Enzyme compositions and use thereof for wound healing |
| US10350278B2 (en) | 2012-05-30 | 2019-07-16 | Curemark, Llc | Methods of treating Celiac disease |
| US10238719B2 (en) | 2014-10-10 | 2019-03-26 | Rochal Industries, Llc | Compositions and kits for enzymatic debridement and methods of using the same |
| US20160101166A1 (en) | 2014-10-10 | 2016-04-14 | Rochal Industries, Llp | Compositions and kits for treating pruritus and methods of using the same |
| US9592280B2 (en) | 2014-10-10 | 2017-03-14 | Rochal Industries Llc | Compositions and kits for enzymatic debridement and methods of using the same |
| US11541009B2 (en) | 2020-09-10 | 2023-01-03 | Curemark, Llc | Methods of prophylaxis of coronavirus infection and treatment of coronaviruses |
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|---|---|---|---|---|
| US2917433A (en) * | 1956-04-02 | 1959-12-15 | Rystan Company | Stable aqueous papain topical compositions |
| US3892853A (en) * | 1967-05-22 | 1975-07-01 | Aloe 99 & 0 Inc | Stabilized aloe vera gel and preparation of same |
| GB1390541A (en) * | 1971-04-14 | 1975-04-16 | Otsuka Kagaku Yakuhin | Anti-inflammatory compositions |
| US3878197A (en) * | 1972-12-13 | 1975-04-15 | Ray H Maret | Process for preparing extracts of aloe vera |
| US4361551A (en) * | 1979-11-05 | 1982-11-30 | Riker Laboratories, Inc. | Method of enzymatic debridement |
-
1984
- 1984-01-18 EP EP19840900913 patent/EP0133438A1/en not_active Withdrawn
- 1984-01-18 WO PCT/US1984/000079 patent/WO1984002846A1/en unknown
- 1984-01-20 CA CA000445785A patent/CA1222453A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106860860A (en) * | 2017-03-03 | 2017-06-20 | 钱安坤 | The new opplication of polyzyme tablets |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1984002846A1 (en) | 1984-08-02 |
| EP0133438A1 (en) | 1985-02-27 |
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