WO1993001819A1

WO1993001819A1 - Use of silicon compounds for preventing traumatic injuries

Info

Publication number: WO1993001819A1
Application number: PCT/US1992/005179
Authority: WO
Inventors: Karl E. Wiegand
Original assignee: Ethyl Corporation
Priority date: 1991-07-15
Filing date: 1992-06-16
Publication date: 1993-02-04
Also published as: JPH06509103A; CA2111972A1; EP0594659A1

Abstract

A method for the treatment, prevention or delay of traumatic injury to the tissue of an animal, especially in humans, equines and the like, comprising treating said animal with an effective amount of silicic acid produced by said animal from a silicon compound administered to said animal.

Description

USE OF SILICON COMPOUNDS FOR PREVENTING TRAUMATIC INJURIES

Field of Invention

This invention relates to the prevention and reduction of susceptibility to traumatic injury by the administration of silicon compounds.

Background of Invention

While it has long been recognized that certain diseases such as those associated with genetic defects and dietary deficiency states, such as scurvy and rickets, lead to increased susceptibility to traumatic injury, the notion of administering a substance to a normally nourished and otherwise physically fit animal or person to reduce susceptibility to trauma is unusual.

A number of silicate compounds have been reported to elevate blood, serum, plasma or urine levels of silicon when administered orally or by injection. These include sodium silicate, magnesium silicate, amorphous sodium aluminosilicate, and sodium zeolite A. Behnke and Osborn showed that sodium zeolite A was particularly effective in this regard. See Behnke, et al., Food. Cosm. Toxicol.. 17, 123-127, (1979).

It is also well known that the form of silicon found in the blood is monosilicic acid [Si(OH)₄], regardless of the source of silicon. See E. M. Carlisle, Silicon. 'Trace Elements in Human and Animal Nutrition". Vol.2, W. Merz, ed. Academic Press, Inc., Orlando, 1986, Ch. 7, pp. 373-390.

Over the years, a wide variety of experiments have been conducted throughout the world utilizing zeolites of many different types in the feeding of animals for varying reasons. Most of these experiments have been in animal nutrition or in increasing the production of food animals or their food products. Most of the animals fed zeolites have been poultry, cattle, sheep and swine. Zeolites fed to the animals were mainly naturally occurring or processed zeolites found in nature. Although some degree of success in some areas was achieved, most of the results were unfavorable.

C. Y. Chung, et al., Nongsa Sihom Youngu Pogo 1978, 20 (Livestock) pp. 77-83, has provided information on the effects of cation exchange capacity and particle size of zeolites on the growth, feed efficiency and feed materials utilizability of broilers or broiling size chickens. Supplementing the feed of the broilers with naturally occurring zeolites, such as clinoptilolite, produces an increase in body weight gain. Chung et al. also reported that earlier results at the Livestock Experiment Station (1974, 1975, 1976 - Suweon, Korea) showed no significant difference when 1.5, 3, and 4.5 percent zeolite was added to chicken layer diets. Canadian Patent No.939,186 (U.S. Pat. No.4,393,082 issued July 12, 1983) discloses the use of zeolites having exchangeable cations as a feed component in the feeding of urea or biuret non-protein nitrogen (NPN) compounds to ruminants, such as cattle, sheep and goats. Natural and synthetic as well as crystalline and non-crystalline zeolites are disclosed. Zeolites tested using in vitro techniques included natural zeolites, chabazite and clinoptilolite and synthetic zeolites X, Y, F, J, M, Z and A. Zeolite F was by far the most outstanding. Zeolite A was substantially ineffective.

Experiments have been in progress in Japan since 1965 on the use of natural zeolite minerals as dietary supplements for poultry, swine and cattle. Significant increases in body weight per unit of feed consumed and in the general health of the animals has been reported (Minato, Hideo, Koatsugasu 6:536, 1968).

Reductions in malodor were also noted.

U.S. Pat. No. 4,847,085 discloses a method of improving the quality of the bones and/or increasing the bone strength of animals, including humans, cattle, sheep, goats, swine and poultry, without deleterious effects on the animals or products of the animals by adding a small, effective amount of zeolite to the feed of the animals or directly to the animals in the form of a capsule, tablet or the like. Zeolites consist basically of a three-dimensional framework of Si0₄ and A10₄ tetrahedra. The tetrahedra are cross-linked by the sharing of oxygen atoms so that the ratio of oxygen atoms to the total of the aluminum and silicon atoms is equal to two, i.e., 0/(Al+Si) =2. The electrovalence of each tetrahedra containing aluminum is balanced by the inclusion in the crystal of a cation, for example, a sodium ion. This balance may be expressed by the formula Al/Na= 1. The spaces between the tetrahedra are occupied by water molecules prior to dehydration. There are a number of different types of zeolites. Some zeolites are found in nature and can also be made synthetically. Other zeolites are made only synthetically. Zeolite A is not found in nature and is made only synthetically.

As noted above, U.S. Pat. No. 4,847,085 discloses the nutritional uses of zeolites to strengthen bone. That patent references the variety and types of zeolites useful in the disclosed method and processes used to prepare such zeolites. It is an important object of this invention to provide a method for treating, preventing or delaying the effects of traumatic injury to the tissues of animals, including humans, by treatment of the animals with a relatively small amount of silicic acid produced by administering to the animal to be subjected to trauma- producing conditions metal silicates or aluminosilicates, especially zeolites. It is an object of the invention to provide an animal treatment or food containing zeolite, which inhibits the effects of traumatic injury in animals, especially humans.

Another object of the invention is to provide a process for the treatment and/or prevention of the effects of traumatic injury to both hard and soft tissue in animals wherein an effective amount of zeolite is added to the diet of the animal.

Still another object of the invention is to effectively treat, prevent or delay traumatic injury to the tissue of animals without causing any deleterious effects in the animals.

Yet a further object of the present invention is to treat, prevent or delay the traumatic injury to the tissue of equine ammals.

Other objects and advantages of the invention will be more fully understood from a reading of the description and claims hereinafter.

Summary of the Invention

The present invention relates to a method of treating, preventing or delaying the traumatic injury to the tissue of animals, especially humans, by treating the animal with an effective amount of silicic acid produced by administering to the animal a silicon-containing compound.

Description of the Preferred Embodiments

It has been discovered that by treating animals exposed to conditions known to generate both hard and soft tissue traumatic injury with silicic acid that such injury is prevented or inhibited (delayed) from occurring. The silicic acid preferably is formed after administering to the animal to be subjected to trauma-causing conditions a physiologically acceptable silicon-containing compound that results in the formation (within the animal) of an effective amount of silicic acid. The silicon-containing compounds employed in this invention are those that are non-toxic and physiologically acceptable and, when administered to the animal, provide the animal with a source of silicic acid. Thus, the silicon-containing compounds can be entirely inorganic or organic silicon compounds. Concerning the latter, silicate esters are preferred and orthosilicates are particularly preferred, i.e., compounds of the formula Si(OR)₄ where R is an organic radical, such as to C₆ linear or branched alkyl (methyl, ethyl, or n-propyl). More than one type of R group may be combined. Concerning the former compounds, metal alumino- silicates are preferred. These include metals of Group IA, such as sodium or potassium, and metals of Group HA, such as calcium and magnesium. Examples of such compounds are potassium aluminosilicate, sodium aluminosilicate, calcium aluminosilicate and magnesium aluminosilicate. The zeolites, particularly zeolite A, are included within such class of inorganic silicates.

It has been found that by administering a small amount of silicon-containing compounds daily, sufficient silicic acid is produced that trauma-induced injury is prevented, inhibited or made less severe. When sodium zeolite A is used, 0.25% to 3.0% of the total food ingested by the animal is effective in this respect.

Administration may be by way of pellets, powder, tablets or capsules.

Traumatic injury among race horses is well known to be a common occurrence. In order to demonstrate the effectiveness of the method of this invention in preventing, inhibiting or treating the incidence of traumatic injury to the tissue of animals by treatment of such animals that have been subjected to conditions that have been shown to cause traumatic tissue injury, the following treatments were carried out. In the following examples, the silicic acid was generated within the animal by administering increasing levels of sodium zeolite A to a group of equines and subjecting them to a standardized regimen of training. It should be understood that the following examples are for the purpose of illustration only. They are not intended to limit this invention in any way. EXAMPLE 1 Starting at approximately six months of age, a group of Quarter Horses were administered a diet of concentrate and hay balanced to NRC guidelines [National Research Council (U.S.) (1989) Nutritional Requirements of Horses. National Academy Press, Washington, D.C.] supplemented with varying levels of sodium zeolite A(ZA). Animals were fed twice daily in individual stalls and otherwise allowed to exercise in a dry paddock. ZA constituted approximately 0, 0.66, 1.33, or 2.0 percent of their feed intake. Feed was composed of 75% concentrate and 25% coastal bermuda grass hay. The concentrate portion of the diet was composed of 87% pelleted concentrate (from corn, wheat mids, soybean meal, alfalfa meal, lignin binder, vitamin supplement, ground limestone and trace mineralized salt) and of 13% supplement of sodium zeolite A pelleted with dried alfalfa. Loading of 0, 6.6, 13.3 and 20% sodium zeolite A in the alfalfa pellets was used to allow constant volumes of supplement while varying the dose level of ZA. Feeding rates were increased as the animals grew so as to maintain approximately constant dosing on a body weight basis. Thus, animals were fed approximately 0.2% of their body weight as (zeolite A-containing) supplement each day as part of the concen-trate portion of their diet (including the 0 dose supplement). The concentration of zeolite A in the supplement is from 6% to 20% by weight (this represents a dose of zeolite A of 0.12% to 0.4% as a fraction of the body weight).

To maintain blinding, the treatments were labelled by drawing lots as A, B, D, C, respectively. Horses were randomly assigned to treatment, blocked by sex, weight and body condition score. Males were gelded at 1 year of age. After six months of treatment, animals, now approximately one year of age, were transferred to large forage- containing paddocks and fed again to NRC requirements with a combination of ad libitum hay and concentrate. Twice daily the horses were each provided 1.82 kg per head of concentrate feed (approximately 1% of body weight over a 180-day period). Animals were again provided with 0.2% of their body weight as the zeolite A-containing supplement (including the 0 dose supplement) in this concentrate. The ratio of supplement to the rest of the concentrate was increased to 20:80 to adjust for the changing nutritional requirements in horses of this age.

At the end of the intermediate six-month paddock feeding phase, animals were entered into a breaking/training/ racing program and conditioned to race from a starting gate. After 17 weeks of breaking and training (9 weeks of breaking and 8 weeks of combined long, slow distance and sprint conditioning and gate training), animals entered a racing program. Animals were raced on alternate weeks. During the week of the race, the following schedule was maintained: day 1 - warm up and gallop 1 mile; day 2 - walk 1 hour on the walker; day 3 - warm up, gallop 1/2 mile and sprint 150 yards; days 4 and 5 - walk; day 6 - race; day 7 - stall rest. Races were run at increasing distances as follows: races 1-3, 300 yards; races 4-6, 350 yards; races 7-9, 400 yards. Alternate weeks with no race the weekly schedule was: days 1 and 3 - warm up and gallop 1.5 miles; days 2, 4, 6 and 7 - walk; day 5 - warm up, gallop 1/2 mile and sprint 200 yards.

During this stage of treatment, horses were maintained in individual stalls and fed every 12 hours. The animals were fed a ratio of concentrate to hay of 70:30 sufficient to maintain their body condition. As in the previous stage, the concentrate portion of the diet was composed of a 20:80 ratio of pelleted zeolite A-containing supplement to pelleted concentrate.

The treatment regimen was maintained throughout the study. Trainers, jockeys, veterinarians and other personnel involved in handling, diagnosis and treatment were blinded as to the composition of the treatments.

Beginning on February 7, over a three-month period ending March 29, six groups of animals began their first race, according to their age. Animals were evaluated for injury sustained as a result of trauma induced by the sprinting/ galloping activity of their conditioning and racing.

On May 28, animals were assessed. They were defined to have been injured if as a result of training or racing at some point they were unable to perform at speed as a result of trauma induced by the galloping/sprinting activity. At this point, the beginning horses had completed eight races and the last entries had completed three races. Both soft and hard tissue injuries were counted. Percent injured within each group was assessed as was the distance and the number of strides to injury. One animal sustained an injury in an accident on the walker. It was not included in the analysis. Another animal was injured before entering the galloping/sprinting phase of the study, but recovered sufficiently to continue a normal training/racing activity. This animal was included in the analysis. Use of distance or strides run before first injury allowed comparison regardless of progress within the race schedule.

The incidence of injury versus dose level of ZA in the supplement and the mean distance run before first injury in strides and yards were as follows:

Distance to

Dose (%ZA) Percent Injured 1st Injury - Strides/Yards

0.0 62 8537/41151 6.66 36 13665/65005 13.3 33 15380/71358 20.0 27 14901/68534

Injuries were classified by treatment and number of ammals per group (N) as follows:

Treatment (%ZA)/(N) Injuries 0.0/(13) Fractured Sesamoid

Swollen Hind Leg

Bone Sprain

Sesamoiditis/Possible Fracture

Tied Up

Swollen Hind Legs

Intermittent Lameness in Left Front Leg

6.66/(14) Shin Bucked

Hind End Lameness

Shin Bucked

13.3/(9) Knee Chip/Fractured Sesamoid/ Arthritis Hairline Fracture of Carpal Bone Fractured Distal Cannon

20.0/(11) Possible Knee Chip Bowed Tendon Bowed Tendon Data were collected for horses injured during conditioning or racing. To assess similar situations, only horses injured under the controlled stress of galloping or sprinting were analyzed. Horses were disqualified from the analysis if they were injured due to accidents not associated with athletic events or incapacitated prior to entry into the training/racing phase. Disqualifications were evenly distributed across treatments and due to the following causes not related to treatment:

1) Lame right front leg. (Occurred during breaking.) 1 horse - Treatment D.

2) Physitis related to conformation (genetic origin - same sire). 1 each - Treatment B and C.

3) Osteochondrosis. (Present upon arrival.) Treatment D.

4) Fractures - chipped knee, sesamoid. (Occurred during breaking.) 1 each - Treatments A and D.

Clearly, treatment led to reduction in both hard and soft tissue injuries in a dose related manner.

EXAMPLE 2

Blood was drawn from horses at intervals throughout the study and analyzed for its silicon content. The method of Gitelman and Alderman was used to determine the level of silicon in the plasma. Gitelman, H.J. and Alderman, F.R., 1991, "Determination of silicon in biological samples using electrothermal atomic absorption spectrometry", J. Analytical Atomic Spectrometry. 5:687. Zeolite A treatment was seen to increase the plasma silicon level in a dose dependent manner.

Samples were taken just prior to feeding (T=0), and at 1, 3, 6 and 9 hours after feeding. The mean of the evenly spaced samples at 0, 3, 6 and 9 hours was used to calculate the mean plasma silicon level.

Plasma silicon levels after 84 days of treatment were: P as a Si m

As can be seen from the Example, the treatment leads to a dose related increase in the mean plasma level of silicon in treated horses. The increase of systemic silicon level is associated with the reduction of susceptibility to traumatic ° injury noted in Example 1.

It will be recognized by those skilled in the art that the usefulness of this invention is general. This is due to the common elements of traumatic injury, regardless of cause. Accordingly, the usefulness of this invention is not limited to athletic injury. Other applications include improved resistance to tissue damage in animals such as poultry, cattle, horses, pigs and humans during transportation, improved resistance to traumatic injury due to falls and so on.

Claims

In the Claims:

1. A method for the prevention or delay of hard or soft tissue physical trauma in an animal, comprising treating said animal with an effective amount of silicic acid produced by said animal from a silicon compound administered to said animal.

2. The method according to Claim 1 wherein said tissue is hard tissue.

3. The method according to Claim 1 wherein said tissue is soft tissue.

4. The method according to Claim 1 wherein said silicon compound is an organic silicon compound.

5. The method according to Claim 1 wherein said silicon compound is an inorganic silicon compound.

6. The method according to Claim 5 wherein said silicon compound is zeolite.

7. The method according to Claim 5 wherein said zeolite is zeolite A.

8. A method for the prevention or delay of hard or soft tissue physical trauma in an animal, comprising treating said animal with an effective amount of silicic acid produced by said animal from zeolite A administered to said animal.

9. The method according to Claim 8 wherein said animal being treated s a human being.

10. The method according to Claim 8 wherein said animal being treated s equine, bovine, canine, feline, swine or poultry.

11. The method according to Claim lOwherein said animal is equine.

12. A method for the prevention or delay of hard or soft tissue physical trauma in a human being, comprising treating said human being with an effective amount of silicic acid produced by said human being from zeolite A administered to said human being at about 0.25 to about 3.00 weight percent of the daily food intake of said human being.

13. The method according to Claim 12 wherein the amount administered is from 0.12 to 0.4 percent of body weight.

14. The method according to Claim 12 wherein said zeolite A is administered in tablet, pelleted, powdered or capsule form.