Patent Publication Number: US-5250300-A

Title: Method for treating digestive organ disorders of domestic animals

Description:
The present invention relates to a liquid internal medicine for domestic animals, which is prepared from a raw material of an extract of Stevia stems, and to a method of preparing the same. More precisely, it relates to a liquid internal medicine for domestic animals, which is obtained by fermenting an extract from Stevia stems and is especially effective for disorders of digestive organs, and also to a method of preparing such a liquid internal medicine. 
     BACKGROUND OF THE INVENTION 
     Use of a Stevia extract as a sweetening agent has been well-known prior to completion of the present invention. 
     The present inventor has participated in the study of extracts from Stevia for many years, and he has already developed various inventions and filed patent applications to claim them. For instance, there may be mentioned a method of ripening a concentrated liquid, extracted from Stevia leaves by a special method, to prepare a sweetener (Japanese Published Kokai No. 3-177959); a horticultural manure obtained by fermenting an extract from a mixture of leaves and Stevia stems and a method of preparing the same (Japanese Published Kokai No. 3-220109); a bath lotion obtained by fermenting an extract from Stevia stems and a method of preparing the same (Japanese Published Kokai No. 3-151321); and a remedy for skin diseases and blood circulation promoting agent, obtained by concentrating, fermenting and ripening an extract from completely ripened Stevia stems, and a method of preparing the same (Japanese Published Kokai No. 4-66535). 
     The present inventor further researched and developed the above-mentioned inventions, whereupon he has found that a substance obtained by concentrating, fermenting and ripening a Stevia extract is useful as an external medicine for domestic animals such as horses, cows and oxen, goats, pigs and chickens; especially for preventing and curing disorders of the digestive organs, for improving the quality of their meat, for promoting the estrous cycle and the establishment of their menstrual function, and for improving the quality of their milk and eggs. On the basis of these findings, he has completed the present invention. 
     SUMMARY OF THE INVENTION 
     One object of the present invention is to provide a liquid internal medicine for domestic animals that is free from any synthetic chemicals or drugs, which contains only one natural component, which provides excellent pharmaceutical effectiveness for disorders of the digestive organs of domestic animals, and has remarkable effectiveness in improving the quality of products from them. Another object of the present invention is to provide a method of preparing such a liquid internal medicine for domestic animals. 
     Specifically, there is provided, in accordance with the present invention, a liquid internal medicine for domestic animals, which contains a liquid obtained by ripening a fermented and concentrated liquid extract from the stems of Stevia as an active ingredient. 
     There is also provided, in accordance with the present invention, a method of preparing a liquid internal medicine for domestic animals, in which a liquid extract from matured stems of Stevia plants is concentrated and fermented, and the resulting liquid is further ripened. 
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     The most important technical characteristic of the present invention is the point of use of a product, obtained by concentrating, fermenting and further ripening a liquid extract from completely matured stems of Stevia plants, as an internal liquid medicine for domestic animals. 
     Through the present inventor&#39;s research, it has been found that Stevia stems contain microorganisms which are not in Stevia leaves, that a product obtained by drying and powdering the stems and boiling the powdered stems in water to give a concentrated liquid, followed by heating, fermenting and ripening the liquid, preferably in a closed tank, has an excellent blood circulation promoting function and an excellent pharmaceutical effect, and that the ripened product thus obtained is applicable to various disorders of the digestive organs of domestic animals to cure them and thereby improve the quality of the products from the treated domestic animals. 
     The liquid internal medicine for domestic animals of the present invention may be introduced to domestic animals as a drink, whereby the blood circulation of the animals will be promoted and the disorders of their digestive organs may be cured. The resultant physical constitution of the thus treated domestic animals will markedly improve. As a further result, the quality of livestock products from these animals will be improved. As a characteristic aspect of the present invention, the raw material for preparing the medicine is, as mentioned above, a liquid obtained by concentrating, fermenting and ripening an extract from only the stems of Stevia, so that the medicine has a potent curative effect on various disorders of the digestive organs of domestic animals, thereby improving the physical constitution of the treated animals. 
     Another characteristic aspect of the present invention is to use completely matured stems of Stevia plants as raw material for the medicine. 
     Precisely, Stevia as referred to herein is a perennial plant of Compositae (Asteraceae), which is native to Paraguay and Brazil in South America and is called Stevia Rebaudiana Bertoni. Stevia seedlings or cuttings are planted from April to May. Seed seedlings of Stevia are harvested two or three times a year while the leaves thereof are young and weak. 
     However, the Stevia stems to be used in the present invention should not be from such young and weak plants, since the pharmaceutical potency of them would not yet be sufficient. Preferably, matured Stevia stems harvested only once a year from October to November are to be used in the present invention. The harvested Stevia plants are dried at about 70° to 80° C. for 24 hours; they are grouped into leaves, stems and branches; only the stems are powdered to a size of 15 μm or less, preferably from about 1 to 8 μm; and the resulting powder is boiled for extraction. Stevia leaves contain components of a sweetener but contain few components having any pharmaceutical effect such as the intended liquid internal medicine. Therefore, the leaves are not suitable for use in the present invention. 
     Concentration, fermentation and ripening of the thus harvested Stevia stems may be implemented as described in the example below. 
     (1) Six liters of water are poured into an iron or stainless-steel pot and heated to boiling. Then, the heat is stopped, and one kg of the above-mentioned mixed powder of dried and powdered Stevia stems is gradually added to the container with gentle stirring. Next, heating is restarted and the whole is boiled for about one hour with stirring. 
     (2) The boiled-down raw material is separated into a liquid and a residue with a squeezer. The thus obtained first liquid (3 to 4 liters) is stored in a tank (concentrating pot). 
     (3) Next, about 4 liters of water are added to the above-mentioned iron or stainless steel pot and heated, and heating is stopped when the water reaches a boil. Then, the above-mentioned first squeezed residue is added thereto, mixed, heated and boiled down for about one hour. 
     (4) The thus boiled-down raw material is again separated into a liquid and a residue with a squeezer. The thus obtained second liquid is about 3 liters. 
     (5) The second liquid is put in the tank (concentrating pot) containing the above-mentioned first liquid, mixed and boiled down for about 3 to 4 hours. After the concentrated liquid mixture has boiled-down to about one liter, the concentration process is finished. The sugar degree of the product after this process is from 20 to 25 degrees. 
     (6) The thus obtained concentrated liquid is filtered, put in a storage tank and fermented and ripened therein at a temperature of from 15° to 30° C., preferably from 15° to 25° C., for a period of time from 90  to 360 days, preferably from 180 to 360 days. Yeast is used for fermentation. 
     General analysis of the components constituting the ripened product was carried out by Nippon Foodstuff Sanitation Association, an authorized examination agency as designated by the Japan Welfare Minister, on the basis of the Japan Foodstuff Sanitation Law and the Drugs, Cosmetics and Medical Instruments Law. The results of Test No. 01-4651 and No. 01-6559 are as follows: 
     
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General Analysis of Components (per 100 g of sample):                     
______________________________________                                    
Energy                   47      Kcal                                     
Water                    84.2    g                                        
Protein                  3.6     g                                        
Lipid                    0.4     g                                        
Carbohydrate (Saccharide)                                                 
                         7.3     g                                        
Ash                      4.5     g                                        
Calcium                  120     mg                                       
Iron                     1.3     mg                                       
Sodium                   22      mg                                       
Potassium (by atomic absorption metric method)                            
                         2200    mg                                       
Phosphorus (by molybdenum blue method)                                    
                         200     mg                                       
Retinol                  0                                                
β-carotene          23      μg                                    
Vitamin A efficacy       13      IU                                       
Vitamin B.sub.1          0                                                
Vitamin B.sub.2          0.21    mg                                       
Vitamin C (by high performance liquid                                     
                         0                                                
chromatography)                                                           
Niacin (by microorganismic determination)                                 
                         2.4     mg                                       
Arsenic (as As.sub.2 O.sub.3) (by Gutzeit&#39;s method, with                  
                         Not detected                                     
note of the Sanitation Examination Method as                              
                         (detection limit                                 
edited by the Nippon Pharmaceutical                                       
                         of 0.1 ppm)                                      
Association)                                                              
Heavy Metal (as Pb) (Heavy Metal Test                                     
                         Not higher than                                  
Method, by Official Regulation of Food                                    
                         10 ppm                                           
Additives, 5th Ed.)                                                       
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     For concentration, a multi-stage concentration process comprising two or more concentration steps may be employed for more effective extraction of the active ingredient. However, the performance obtained through four or more concentration steps is not especially significant in view of the concentration of the final extract but is rather economically disadvantageous. 
     Where the liquid internal medicine for domestic animals of the present invention thus obtained is perorally applied to domestic animals, it may be diluted before use to a mixture from 1/5 to 1/50, preferably from 1/10 to 1/15, with water or a soft drink, in accordance with the condition of the animal. 
     Since the liquid internal medicine for domestic animals of the present invention is totally composed of a natural Stevia extract only, it is free from any harmful side effects when absorbed into the body of an animal. After the animal consumes it, the animal&#39;s blood circulation is promoted so that not only may the disorders of the animal&#39;s digestive organs be cured but the physical constitution of the animal may also be improved. 
     An acute toxicity test (LD 50 ) of the liquid internal medicine for domestic animals of the present invention was carried out by the Nippon Foodstuff Sanitation Association, an authorized examination agency as designated by the Japan Welfare Minister, on the basis of the Japan Foodstuff Sanitation Law and the Drugs, Cosmetics and Medical Instruments Law. The results of Test No. 01-4651-2 are as follows: 
     1. Object of Test: 
     Acute toxicity test (LD 50 ) 
     2. Substance to be Tested: 
     Concentrated Stevia liquid 
     3. Animals Used: 
     Five-week old male ddy-line mice; three groups of ten mice each 
     4. Test Method: 
     Administration of test substance: Healthy mice were selected and no feed was given thereto for 18 hours. Then, a thick test liquid was perorally administered thereto with a Magensonde. 
     Amount administered: The test liquid was administered to each group having ten mice, in an amount, respectively, of 1 ml/20 g, 0.75 ml/20 g and 0.5 ml/20 g. 
     Breeding condition: After administration of the test liquid (Day 0), the mice were bred under constant temperature and humidity for 7 days, while water and feed were added thereto freely. 
     5. Observation of Condition of the Mice During the Test: 
     All mice in the first group, to which the maximum amount of 1 ml/20 g of the test liquid had been administered, displayed depression of spontaneous movement and depression of respiration for 30 minutes immediately after the administration of the test liquid, but all of them recovered to normal condition within 30 minutes thereafter. 
     The mice in the second group, to which 0.75 ml/20 g of the test liquid had been administered, showed slight depression of spontaneous movement immediately after the administration of the test liquid, but they recovered to normal condition within 20 minutes after administration of the same. 
     6. Test Result: 
     The weight of each mouse bred under the above-mentioned condition was measured every day, and their general condition was observed every day. During the test period, the weight of each mouse increased normally, and there was no special change found in any of the tested mice during the test period of 7 days. 
     From the above-mentioned results, the value of LD 50  of the concentrated Stevia liquid as tested above is 50 ml/kg or more, and the acute toxicity of the liquid is presumed to be extremely low. 
     The liquid internal medicine for domestic animals of the present invention was confirmed to have a pharmaceutical and medical effect on the following animal diseases. 
     Indications for the Medicine of this Invention are 
     Indigestion, acceleration of digestion, hyperacidity, diarrhea, loose passage, stomatitis, astriction, promotion of appetite, intestinal disorders, improvement of hair gloss and meat quality, promotion of the estrous cycle and the establishment of the menstrual function, improvement of milk quality. 
    
    
     The present invention will be explained in more detail by way of the following examples, which, however, are not intended to restrict the invention. 
     EXAMPLE 1 
     Matured Stevia plants were harvested at the beginning of November and were dried in a tobacco drier having an area of 6.6 m 2 , at 75° +/- 3° C. for 24 hours under the condition of an air flow rate of 30 m 3  /min. 
     Next, the plants were lightly beaten with a bar so as to separate them into stems, leaves, branches and impurities. Only stems were collected. The stems were cut with a cutter into small pieces of about 3 to 5 cm, then powdered twice with a Hitachi grinder and thereafter sieved to a fine powder having a mean particle size of 5 μm. 
     Next, 6 liters of water was poured into an iron pot and heated. After the water reached a boil, the heat was stopped. Then, 1 kg of the previously prepared fine powder of Stevia stems was gradually added to the pot with gentle stirring and was boiled down with stirring for one hour. 
     This was put into a Nishikawa squeezer and separated into a Stevia liquid and a residue. The thus obtained first liquid was about 4 liters, which was put in a tank (concentrating pot). 
     Next, 4 liters of water was put into the above-mentioned iron pot and heated. After the water reached a boil, the heat was stopped. The previously separated residue was gradually added to the pot and heating was again started. The whole was then boiled down for about 1 hour. This was put in the above-mentioned squeezer and separated into a Stevia liquid and a residue. The thus obtained second liquid was about 3 liters, and this was put in the above-mentioned tank (concentrating pot) containing the previous first liquid and the two were blended. 
     Next, the tank was heated and the content therein was boiled down. After about 4 hours, the concentrated liquid mixture was boiled down to about 1000 cc. The thus concentrated liquid was filtered through a cotton bag, and the resulting filtrate was put in a storage tank made of stainless-steel. This was then fermented and ripened therein at 25° C. for 360 days, whereupon the resulting liquid had a sugar degree of 21 degrees. 
     The liquid internal medicine thus obtained was a brownish-green liquid having a sweet aroma and an extremely low viscosity. 
     EXAMPLE 2 
     Examples of administration of the liquid internal medicine for domestic animals of the present invention are mentioned below. 
     
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Kind of                                                                   
Domestic     Method of Peroral                                            
Animals                                                                   
      Condition                                                           
             Administration Results                                       
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Beef cattle                                                               
      Chronic                                                             
             20 cc of 20% aqueous solution;                               
                            The disorder was eased, and                   
      tympanites                                                          
             twice a day    the weight increased, both in 30 days.        
Beef cattle                                                               
      Hypogenesis                                                         
             20 cc of 20% aqueous solution;                               
                            The quality of meat and the hair gloss        
             twice a day    improved, and the weight increased,           
                            both in 60 days                               
Beef cattle                                                               
      Diarrhea                                                            
             20 cc of 20% aqueous solution;                               
                            Cured in 6 days.                              
             twice a day                                                  
Pig (with                                                                 
      Normal 20 cc of 20% aqueous solution;                               
                            It farrowed healthy and well 13 baby          
young)                                                                    
      condition                                                           
             twice a day    pigs. In general, ordinary baby pigs          
                            often have loose bowels during the            
                            weaning period. However, all 13               
                            baby pigs from the mother pig were            
                            free of such diarrhea.                        
Pig (young                                                                
      Normal 20 cc of 10% aqueous solution;                               
                            It did not have loose bowels during           
pig)  condition                                                           
             twice a day    the weaning period, and it grew well.         
Pig (young)                                                               
      Hypogenesis                                                         
             20 cc of 20% aqueous solution;                               
                            The weight increased, and the quality         
pig)         twice a day    of meat and the hair gloss improved.          
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     In accordance with the present invention, there is provided a liquid internal medicine for domestic animals containing only a fermented and concentrated liquid from an extract of Stevia stems, and the medicine for domestic animals has effective pharmaceutical activities for indigestion, acceleration of digestion, hyperacidity, diarrhea, loose passage, stomatitis, astriction, promotion of appetite, intestinal disorders, improvement of hair gloss and quality of meat, promotion of the estrous cycle and the establishment of the menstrual function, and improvement of milk quality. 
     The medicine for domestic animals of the present invention can easily be prepared by powdering stems of Stevia, concentrating an extract from the powder by a multi-stage process, and fermenting and ripening the resulting concentrate. 
     While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.