US20030133923A1 - Composition for preventing the formation and enhancing the breakdown of bezoars in animals and humans - Google Patents

Composition for preventing the formation and enhancing the breakdown of bezoars in animals and humans Download PDF

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Publication number
US20030133923A1
US20030133923A1 US10/388,690 US38869003A US2003133923A1 US 20030133923 A1 US20030133923 A1 US 20030133923A1 US 38869003 A US38869003 A US 38869003A US 2003133923 A1 US2003133923 A1 US 2003133923A1
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bezoar
fat
animal
emulsifying agent
human
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US10/388,690
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Mark Cook
Beth Drake
Leonard Girsh
Janet Jackson
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    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/158—Fatty acids; Fats; Products containing oils or fats
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/189—Enzymes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • 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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A61K31/77—Polymers containing oxygen of oxiranes
    • 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)

Definitions

  • the present invention relates to methods for preventing gastrointestinal bezoar formation and for reducing the size of a gastrointestinal bezoar in humans and non-human animals.
  • Bezoars are any of several types of solid or semi-solid masses of indigestible material found in the stomach of humans and many animals including cattle, cats, rats, rabbits, and non-human primates.
  • Trichobezoars contain a mesh of ingested hair; phytobezoars contain fruit or vegetable matter. Other combinations of indigestible materials such as plastic bags are also known.
  • Trichobezoars are known to entrap undigested dietary fat in the hair mesh. Qureshi, N.
  • Bezoars typically do not pass through the intestines unless treated or surgically removed. Sometimes small bezoars can be removed from an internal passageway through a scope placed through the mouth and into the stomach.
  • Non-surgical remedies include fiber-supplemented feed and petroleum jelly based oral medicament for lubricating the internal passageway. These remedies can soften a bezoar, but do not actually break it up. Bezoars can become impacted if the treatment does not sufficiently soften the hairball.
  • U.S. Pat. No. 6,080,403 describes a protease-containing hairball remedy and method for using the same. However, accumulated fat can undesirably interfere with proteolytic or acid hydrolysis by preventing aqueous gastric components (e.g., proteases and gastric acids) from contacting the hairball.
  • aqueous gastric components e.g., proteases and gastric acids
  • a method for reducing the size of a gastrointestinal bezoar in a human or non-human animal susceptible to bezoar formation includes the step of administering to the animal a food grade agent for emulsifying fat in an amount sufficient to reduce the size of the bezoar so that the bezoar can pass out of the animal's digestive system.
  • a food grade agent for emulsifying fat is administered to the animal in an amount sufficient to prevent formation of bezoars, or at least to prevent formation of bezoars at or above a size that becomes trapped in the animal's digestive system.
  • the undigested fat trapped in the bezoar mesh is digested by an agent for emulsifying fat.
  • agents useful in the method are available as inexpensive food-grade ingredients, so that adding the agents to an animal's diet adds little cost to the final food or feed product.
  • the fat content of a bezoar can exceed about 20% by dry weight.
  • the inventors here demonstrate that treating a hairball with a food grade fat emulsifying agent can reduce hairball size by degrading the enmeshed fat. From this observation, a skilled artisan will appreciate that treatment of a hairball in the stomach of a human or non-human animal with a food grade fat emulsifying agent can reduce its size and permit the hairball to pass from the animal's digestive system without requiring surgical or endoscopic intervention.
  • the present invention provides a method of using food grade fat emulsifiers to reduce the size of any bezoar that comprises enmeshed undigested fat and thereby enhance the breakdown of the bezoar by orally administering to a human or non-human animal a food grade fat emulsifying agent at an amount effective to reduce the size of the bezoar.
  • the bezoar can be in its early formation stage or can be fully formed.
  • the reduction method can function to prevent the formation of full size bezoars such that the human or non-human animal may never note the existence of a bezoar.
  • the reduction method can function therapeutically to reduce the impact of a bezoar on the animal.
  • the fat emulsifier can be a food grade surfactant including various soaps and various detergents such as a Tween surfactant, preferably Tween 20 or Tween 80, most preferably Tween 80, lecithin such as phosphotidyl choline, and bile salts.
  • a Tween surfactant preferably Tween 20 or Tween 80, most preferably Tween 80, lecithin such as phosphotidyl choline, and bile salts.
  • Such fat emulsifier can also be an enzyme that degrades lipids or fats, such as a lipase which includes but is not limited to lipoprotein lipases, hormone sensitive lipases and phospholipase. Two or more different fat emulsifiers can be combined for use in the methods of the invention.
  • the amount of the fat emulsifying agent to be administered will vary depending upon the extent of treatment desired, but should generally be between about 0.01% and 5% of the diet by weight to reduce the size of a fully formed bezoar, more preferably between about 0.1% and 2% by weight, and most preferably about 1% by weight. Amounts greater than about 5% are considered no more effective than lower amounts, but are not considered to be harmful to the subject.
  • a bezoar need not be completely degraded to consider the method a success. It is sufficient that a bezoar is broken down into pieces of sufficiently small size to pass through the animal's digestive tract. In some cases, it may even be adequate for the bezoar to be reduced in size only enough to relieve discomfort.
  • the present invention also includes a method for reducing accumulation of undigested dietary fat in a forming bezoar.
  • the method can be, but need not be, sufficiently effective as to completely prevent bezoar formation.
  • Such methods include the step of administering to the animal a food-grade fat emulsifier as described above at an amount sufficient to reduce or prevent undigested dietary fat from becoming enmeshed in the bezoar mesh.
  • the amount administered is sufficient if the fat either cannot accumulate in a forming bezoar or accumalates to a reduced extent than in an untreated human or non-human animal.
  • the amount of fate enmeshed in a bezoar is reduced, the components of the hairball can be more readily dispersed.
  • the present invention also includes a method for reducing the size of a bezoar by using a fat emulsifier in combination with an exogenously administered protease.
  • the fat emulsifier makes the hairball more readily dispersed while the protease breaks down the protein matrix.
  • the applicants simulated in vitro the conditions found in a human animal stomach (pH 3.0, 100° F. for a fixed period of time, here 24 hours) to demonstrate the effect on a hairball of varying amounts of a fat-emulsifying agent.
  • the example demonstrates that the treatment emulsified the enmeshed fat and degraded the hairball to a lesser or greater extent depending on the concentrations of the agent used, up to a plateau level.
  • Tween 80 (lot#1373A, Uniqema, Wilmington, Del.) was dissolved in 150 ml acidified water (pH 3.0) at a concentration of 0%, 5%, 10%, 15%, and 20%.
  • a feline hairball (1.0-1.1 g) was then added to each of the five solutions. The mixtures were incubated at 100° F. for 24 hours. After incubation, hair lumps (defined as hair not floating free in the liquid) was removed and the liquid was strained through cheesecloth. Free hair and hair lumps were then dried and weighed.
  • % Hair clump wt (g) Free hair wt (g) % enhanced Tween-80 (% total wt) (% total wt) break down 0 0.6238 (84.46%) 0.1148 (15.54%) — 5 0.6273 (79.62%) 0.1606 (20.38%) 5 10 0.2214 (46.22%) 0.2576 (53.78%) 35 15 0.2157 (52.14%) 0.1980 (47.86%) 35 20 0.2290 (48.00%) 0.2480 (51.99%) 35

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Food Science & Technology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Birds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A digestive system bezoar in a human or non-human animal susceptible to bezoar formation can be reduced in size by administering to the animal a food grade agent for emulsifying fat in an amount sufficient to reduce the size of the bezoar so that the bezoar can pass out of the animal's digestive system. In a similar method for preventing bezoar formation in a human or non-human animal susceptible to bezoar formation, a food grade agent for emulsifying fat can be administered to the animal in an amount sufficient to prevent formation of bezoars, or at least to prevent formation of bezoars larger than a size that becomes trapped in the animal's digestive system.
SEQUENCE LISTING
Not applicable.
CROSS-REFERENCE TO RELATED APPLICATIONS
Not applicable.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not applicable.

Description

    BACKGROUND OF THE INVENTION
  • The present invention relates to methods for preventing gastrointestinal bezoar formation and for reducing the size of a gastrointestinal bezoar in humans and non-human animals. Bezoars are any of several types of solid or semi-solid masses of indigestible material found in the stomach of humans and many animals including cattle, cats, rats, rabbits, and non-human primates. Trichobezoars contain a mesh of ingested hair; phytobezoars contain fruit or vegetable matter. Other combinations of indigestible materials such as plastic bags are also known. Trichobezoars are known to entrap undigested dietary fat in the hair mesh. Qureshi, N. H., et al., “Trichobezoar—a condition to think of in case of mobile abdominal mass,” [0001] Irish Med. J. (June 1992). While the incidence of bezoars is generally very low in humans, a somewhat greater risk exists among mentally retarded or emotionally disturbed children, particularly humans who habitually pluck their hair (trichotillomania) and/or eat their hair (trichophagia). Bezoars are commonly referred to as “hairballs” and the terms will be used interchangeably throughout this application.
  • Bezoars typically do not pass through the intestines unless treated or surgically removed. Sometimes small bezoars can be removed from an internal passageway through a scope placed through the mouth and into the stomach. Non-surgical remedies include fiber-supplemented feed and petroleum jelly based oral medicament for lubricating the internal passageway. These remedies can soften a bezoar, but do not actually break it up. Bezoars can become impacted if the treatment does not sufficiently soften the hairball. U.S. Pat. No. 6,080,403 describes a protease-containing hairball remedy and method for using the same. However, accumulated fat can undesirably interfere with proteolytic or acid hydrolysis by preventing aqueous gastric components (e.g., proteases and gastric acids) from contacting the hairball. [0002]
  • Reliable non-surgical methods for reducing the size of bezoars and for preventing their occurrence are needed, as the existing methods are relatively ineffective. [0003]
    • BRIEF SUMMARY OF THE INVENTION
  • The present invention is summarized in that a method for reducing the size of a gastrointestinal bezoar in a human or non-human animal susceptible to bezoar formation includes the step of administering to the animal a food grade agent for emulsifying fat in an amount sufficient to reduce the size of the bezoar so that the bezoar can pass out of the animal's digestive system. In a similar method for preventing bezoar formation in a human or non-human animal susceptible to bezoar formation, a food grade agent for emulsifying fat is administered to the animal in an amount sufficient to prevent formation of bezoars, or at least to prevent formation of bezoars at or above a size that becomes trapped in the animal's digestive system. [0004]
  • It is an object of the invention to reduce the occurrence and severity of bezoars in human and non-human animals. [0005]
  • It is a feature of the invention that the undigested fat trapped in the bezoar mesh is digested by an agent for emulsifying fat. [0006]
  • It is an advantage of the invention that agents useful in the method are available as inexpensive food-grade ingredients, so that adding the agents to an animal's diet adds little cost to the final food or feed product. [0007]
  • Other objects, advantages and features of the invention will become apparent upon consideration of the following detailed description of the invention. [0008]
    • BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
  • Not applicable. [0009]
    • DETAILED DESCRIPTION OF THE INVENTION
  • The fat content of a bezoar, particularly a trichobezoar, can exceed about 20% by dry weight. The inventors here demonstrate that treating a hairball with a food grade fat emulsifying agent can reduce hairball size by degrading the enmeshed fat. From this observation, a skilled artisan will appreciate that treatment of a hairball in the stomach of a human or non-human animal with a food grade fat emulsifying agent can reduce its size and permit the hairball to pass from the animal's digestive system without requiring surgical or endoscopic intervention. [0010]
  • In general, the present invention provides a method of using food grade fat emulsifiers to reduce the size of any bezoar that comprises enmeshed undigested fat and thereby enhance the breakdown of the bezoar by orally administering to a human or non-human animal a food grade fat emulsifying agent at an amount effective to reduce the size of the bezoar. The bezoar can be in its early formation stage or can be fully formed. In the former case, the reduction method can function to prevent the formation of full size bezoars such that the human or non-human animal may never note the existence of a bezoar. In the latter case, the reduction method can function therapeutically to reduce the impact of a bezoar on the animal. [0011]
  • Any food grade fat emulsifier can be used. The fat emulsifier can be a food grade surfactant including various soaps and various detergents such as a Tween surfactant, preferably Tween 20 or Tween 80, most preferably Tween 80, lecithin such as phosphotidyl choline, and bile salts. Such fat emulsifier can also be an enzyme that degrades lipids or fats, such as a lipase which includes but is not limited to lipoprotein lipases, hormone sensitive lipases and phospholipase. Two or more different fat emulsifiers can be combined for use in the methods of the invention. [0012]
  • The amount of the fat emulsifying agent to be administered will vary depending upon the extent of treatment desired, but should generally be between about 0.01% and 5% of the diet by weight to reduce the size of a fully formed bezoar, more preferably between about 0.1% and 2% by weight, and most preferably about 1% by weight. Amounts greater than about 5% are considered no more effective than lower amounts, but are not considered to be harmful to the subject. [0013]
  • A bezoar need not be completely degraded to consider the method a success. It is sufficient that a bezoar is broken down into pieces of sufficiently small size to pass through the animal's digestive tract. In some cases, it may even be adequate for the bezoar to be reduced in size only enough to relieve discomfort. [0014]
  • The present invention also includes a method for reducing accumulation of undigested dietary fat in a forming bezoar. The method can be, but need not be, sufficiently effective as to completely prevent bezoar formation. Such methods include the step of administering to the animal a food-grade fat emulsifier as described above at an amount sufficient to reduce or prevent undigested dietary fat from becoming enmeshed in the bezoar mesh. The amount administered is sufficient if the fat either cannot accumulate in a forming bezoar or accumalates to a reduced extent than in an untreated human or non-human animal. When the amount of fate enmeshed in a bezoar is reduced, the components of the hairball can be more readily dispersed. For such prophylactic bezoar prevention methods, the above-mentioned fat emulsifier amounts for treatment can be effective, though even lower concentrations of a fat emulsifier, in the range of 0.001% to 1% by weight, more preferably in the range of 0.01% to 0.1% by weight, can also be used. [0015]
  • The present invention also includes a method for reducing the size of a bezoar by using a fat emulsifier in combination with an exogenously administered protease. The fat emulsifier makes the hairball more readily dispersed while the protease breaks down the protein matrix. [0016]
  • In the following example, the applicants simulated in vitro the conditions found in a human animal stomach (pH 3.0, 100° F. for a fixed period of time, here 24 hours) to demonstrate the effect on a hairball of varying amounts of a fat-emulsifying agent. The example demonstrates that the treatment emulsified the enmeshed fat and degraded the hairball to a lesser or greater extent depending on the concentrations of the agent used, up to a plateau level.[0017]
    • EXAMPLE
  • Tween 80 (lot#1373A, Uniqema, Wilmington, Del.) was dissolved in 150 ml acidified water (pH 3.0) at a concentration of 0%, 5%, 10%, 15%, and 20%. A feline hairball (1.0-1.1 g) was then added to each of the five solutions. The mixtures were incubated at 100° F. for 24 hours. After incubation, hair lumps (defined as hair not floating free in the liquid) was removed and the liquid was strained through cheesecloth. Free hair and hair lumps were then dried and weighed. [0018]
    % Hair clump wt (g) Free hair wt (g) % enhanced
    Tween-80 (% total wt) (% total wt) break down
    0 0.6238 (84.46%) 0.1148 (15.54%) —
    5 0.6273 (79.62%) 0.1606 (20.38%)  5
    10 0.2214 (46.22%) 0.2576 (53.78%) 35
    15 0.2157 (52.14%) 0.1980 (47.86%) 35
    20 0.2290 (48.00%) 0.2480 (51.99%) 35

Claims (22)

We claim:
1. A method for reducing the size of a gastrointestinal bezoar that comprises enmeshed undigested fat in a human or non-human animal, the method comprising the step of:
orally administering to the animal a food grade fat emulsifying agent in an amount that reduces the enmeshed fat in the bezoar.
2. The method of claim 1 wherein the bezoar treated in the method is fully formed.
3. The method of claim 1 wherein the bezoar treated in the method is not fully formed.
4. The method of claim 1, wherein the fat emulsifying agent is a lipase.
5. The method of claim 4, wherein the lipase is selected from the group consisting of lipoprotein lipases, hormone sensitive lipases and phospholipases.
6. The method of claim 1, wherein the fat emulsifying agent is a surfactant.
7. The method of claim 6, wherein the surfactant is selected from the group consisting of detergents, lecithins, and bile salts.
8. The method of claim 6, wherein the surfactant is Tween.
9. The method of claim 8, wherein the surfactant is selected from the group consisting of Tween 20 and Tween 80.
10. The method of claim 8, wherein the surfactant is Tween 80.
11. The method of claim 7, wherein the lecithin is phosphotidyl choline.
12. The method of claim 1, wherein the fat emulsifying agent comprises at least two agents.
13. The method of claim 1, wherein the fat emulsifying agent is administered in the diet at about 0.01% to about 5% by weight.
14. The method of claim 13, wherein the fat emulsifying agent is administered in the diet at about 0.1% to about 2% by weight.
15. The method of claim 13, wherein the fat emulsifying agent is administered in the diet at about 1% by weight.
16. The method of claim 13, wherein the fat emulsifying agent is administered in the diet at about 0.001% to about 1% by weight.
17. The method of claim 13, wherein the fat emulsifying agent is administered in the diet at about 0.01% to about 0.1% by weight.
18. The method of claim 1, wherein the non-human animal is selected from the group consisting of cattle, cats, rats, rabbits and non-human primates.
19. The method of claim 1, wherein the non-human animal is a cat.
20. The method of claim 1, wherein the bezoar is a trichobezoar.
21. The method of claim 1, wherein the bezoar is a phytobezoar.
22. The method of claim 1, further comprising the step of:
orally administering to the animal a protease in an amount sufficient to break down a protein matrix in the bezoar.
US10/388,690 2001-04-20 2003-03-14 Composition for preventing the formation and enhancing the breakdown of bezoars in animals and humans Abandoned US20030133923A1 (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050084517A1 (en) * 2003-09-12 2005-04-21 Mars Incorporated Food product for hairball treatment
US20080080926A1 (en) * 2006-09-28 2008-04-03 World Wide Stationery Mfg. Co., Ltd. Ring binder mechanism with sliding hinge plate
US10117446B2 (en) 2012-11-15 2018-11-06 Colgate-Palmolive Company Hairball control through dietary mineral limitation

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6080403A (en) 1998-06-18 2000-06-27 Star-Kist Foods, Inc. Protease containing hairball remedy and use thereof
ATE308896T1 (en) * 1999-12-30 2005-11-15 Kemin Ind Inc METHOD FOR IMPROVING ENZYME ACTIVITY

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050084517A1 (en) * 2003-09-12 2005-04-21 Mars Incorporated Food product for hairball treatment
US8128956B2 (en) 2003-09-12 2012-03-06 Mars, Inc. Food product for hairball treatment
US20080080926A1 (en) * 2006-09-28 2008-04-03 World Wide Stationery Mfg. Co., Ltd. Ring binder mechanism with sliding hinge plate
US10117446B2 (en) 2012-11-15 2018-11-06 Colgate-Palmolive Company Hairball control through dietary mineral limitation

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US20020182202A1 (en) 2002-12-05

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