Abstract:
A therapeutic agent which is milk collected from a milk animal which has been immunized by a virus or viruses capable of growing in the digestive tract can be used to prevent a disease such as intractable diseases including multiple sclerosis, acute gastroenteritis and viral hepatitis, which are caused by said virus.

Description:
This application is a continuation of application Ser. No. 06/473,750, filed on Mar. 9, 1983, now abandoned, which is a continuation-in-part of Ser. No. 06/255,808 filed Apr. 20, 1981, now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a therapeutic method, more particularly, to a therapeutic method for diseases such as intractable diseases including multiple sclerosis, acute gastroenteritis, viral hepatitis and the like, which are caused by virus capable of growing in the digestive tract. 
     2. Description of the Prior Art 
     Heretofore, no effective preventive method has been found for intractable neuropathic diseases such as multiple sclerosis, Bechet disease, myasthenia gravis, amyotrophic lateral sclerosis, systemic lupus erythematosus, Parkinson disease, and slow virus infection disease. Corticosteroids such as Prednisolone are only examples which have been practically used. However, they are accompanied by strong side effects. 
     SUMMARY OF THE INVENTION 
     As a result of a long term virological and immunological study on the above-described diseases, it has now been found that these intractable diseases are autoimmune diseases triggered by virus infections and, to prevent such diseases, it is only necessary to avoid the growth of respective virus in a digestive tract. It has also been found that, when a milk animal such as cow or goat, preferably in her pregnancy, is immunized by viruses, lots of anti-virus antibody are contained in the milk, particularly, colostrum and, upon oral administration of the milk such intractable disease or diseases can be considerably prevented. 
    
    
     BRIEF DESCRIPTION OF THE DRAWING 
     FIG. 1 shows the amounts of IgA, IgM and IgG contained in a therapeutic agent for intractable diseases according to this invention. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     A therapeutic agent according to this invention and adapted for the prevention of such intractable diseases may be produced, for example, as follows: 
     An immunization of a milk animal in her 6th-9th month pregnancy is carried out by subcutaneously or intramuscularly inoculating the same animal with virus or virus vaccine every 7 to 14 days and 3 to 6 times in total. The amount of virus or virus vaccine to be inoculated is not specifically limited but its upper limit is determined depending upon side effects which may be caused by the inoculation. As virus vaccine, vaccine of measlesvirus or distempervirus may be employed. Colostrum is collected, preferably, for 1 to 3 days after the birth, to provide a therapeutic agent for the above-described diseases. 
     Similarly, a therapeutic agent for infantile acute gastro-enteritis can be produced by an inoculation of virus such as rotavirus, adenovirus, calicivirus, astrovirus, coronavirus, minireovirus, or parvovirus. On the other hand, a therapeutic agent for viral hepatitis can be prepared by an inoculation of A-type, B-type or Non-A and Non-B type hepatitisvirus. It is also possible to use vaccine in place of virus per se. 
     Milk of a milk animal according to this invention and providing an effect to prevent a disease caused by virus may be applied in any suitable manner, but an oral administration is preferred as it permits intestinal absorption. Thus, the milk is orally administered as it is or after converting it to powder milk through dehydration. 
     The dosage administered will be dependent upon the age, condition and weight of the patient, the state of the disease, kind of concurrent treatment if any, frequency of treatment, and the nature of the effect desired. Generally, a daily dosage measured as milk will be from about 0.1-10 ml per kg of body weight. Normally, from 1-2 ml per kg per day, in one or more applications per day is effective to obtain the desired result. 
     The active ingredient of the milk of this invention can be employed in dosage forms such as tablets, capsules, powder packets, granules, or liquid solutions, suspension, or elixirs, for oral administration. 
     Besides the active ingredient of this invention, the composition will contain a solid or liquid non-toxic pharmaceutical carrier for the active ingredient. In one embodiment of a composition, the solid carrier can be a capsule of the ordinary gelatin type. 
     In another embodiment, the active ingredient can be tableted with or without adjuvants, or put into powder packets. 
     The present invention will be further illustrated in the following examples: 
     EXAMPLE 1 
     A Holstein cow in her 8th-month pregnancy was inoculated subcutaneously with 10 ampoules of attenuated measeles vaccine (Schwarz strain) and 5 ampoules of distemper vaccine (Onderstepoort strain) every 10 days and 5 times in total. After birth, colostrum was collected on each of the first, second and third days. Each colostrum (20 l) thus obtained was subjected to centrifugation at 5,000 rpm for 20 minutes to remove bacteria and fat therefrom. Its supernatant was collected as skim milk. The measles-neutralizing antibody titer of the colostrum obtained on each of the first, second and third days is given in Table 1. 
     
                       TABLE 1______________________________________      Day of milk               Measles-neutralizing      collection               antibody titer______________________________________Immunized    1st day     .sup. 2.sup.4Colostrum    2nd day     2        3rd day    &lt;2Unimmunized  1st day    &lt;2colostrumCommercial              &lt;2milk______________________________________ 
    
     The IgA, IgG and IgM of the colostrum obtained on each of the first, second and third days after the birth are shown in FIG. 1. 
     EXAMPLE 2 
     Colostrum obtained on the first day after the birth of a pregnant cow in a manner similar to that followed in Example 1 was orally administered every morning to four patients affected by multiple sclerosis at a daily dosage of 100 ml for 30 days (1 course). As a control, two patients affected by the same disease were orally administered similarly with the colostrum obtained on the first day after the birth of a pregnant, unimmunized Holstein cow. Results are shown in Table 2 (the patient group administered with a therapeutic agent according to this invention) and Table 3 (control). 
     
                                           TABLE 2__________________________________________________________________________(Patient Group Administered with A TherapeuticAgent According to This Invention)Initials ofpatient,Symptoms before and after administrationage  Before       After        Judgement__________________________________________________________________________S. R.Abasia, deteriorated             After the first course,                          Apparently25 yearsimpressibility, double             abasia and emotional                          effectiveold  vision, spastic paraly-             incontinence improved,sis of limbs, accel-             but progressed againerated reflex of limb             after the stop oftendons, pathologic             administration.reflex (+), cerebellar             Improved again in thesyndrome (+), emotional             second course.incontinence (+),dysuria (+).I. A.Dullness of the lower             After the first course,                          Apparently42 yearslimbs, headache,             dysuria improved but                          effectiveold  progressed hypesthesia             progressed again afterof Th 2 or less and             the stop of adminis-paresthesia, incom-             tration.plete spastic paralysis             In the second course,of all limbs, epileptic             dysuria and numbnessreflex of left body             of the lower limbs(+), dysuria.             improved.N. K.Paresthesia below             Remarkable improvement                          Effective36 yearschest, hypesthesia of             to the sensation,old  Th 6 or less, remark-             particularly, vibra-able progress of             tion sensation, aftervibration sensation of             the first course.both lower limbs,weakened muscle powerof both lower limbs.E. K.Abasia, numbness of             No change observed                          Unchanged30 yearslower limbs, forearms,             after first course ofold  hands and fingers,             administration.progressed sensationparticularly vibrationsensation, of bothlower limbs, accel-erated reflex of lowerlimb tendons, patho-logic reflex (+),pollakiuria.__________________________________________________________________________ 
    
     
                                           TABLE 3__________________________________________________________________________(Control)Initials of Symtoms before and after administrationpatient, age Before       After      Judgement__________________________________________________________________________K. C. Abasia, incontinence              After the first course                         Ineffective37 years of urine, paresthesia              of administration,old   of Th 6 or less,              paresthesia improved. hypesthesia, paresthesia              But, painful convul- of both upper limbs,              sion developed at progressed deep sensa-              upper left limb. tion, accelerated reflex of upper and lower limb tendons, cerebellar syndrome (+).T. T. Tingle feeling at both              No improvement                         Unchanged46 years fingers and heels,              observed after theold   spastic limb paralysis,              first course of pathologic reflex (+)              administration. at both sides, paresthesia below knees of both lower limbs, hypesthesia of upper left limb.__________________________________________________________________________ 
    
     As apparent from the above experiments, a therapeutic agent for intractable diseases of the present invention does not develop side effects and is effective to cure such intractable diseases by its oral administration of about 100 ml a day. 
     EXAMPLE 3 
     A Holstein cow in her 8th-month pregnancy was inoculated subcutaneously with 10 9  /ml of human rotavirus (wa strain) every 10 days and 5 times in total. After birth, colostrum was collected on each of the first, second and third days. Each colostrum (10 l) thus obtained was subjected to centrifugation at 7,000 rpm for 30 minutes to remove bacteria and fat therefrom. Its supernatant was collected as skim milk. The human rotavirus-neutralizing antibody titer of the colostrum obtained on each of the first, second and third days is given in Table 4. 
     
                       TABLE 4______________________________________   Day of milk            Human rotavirus-neutralizing   collection            antibody titer______________________________________Immunized 1st day    5,120colostrum 2nd day    320     3rd day    &lt;160Unimmunized     1st day    &lt;2colostrum______________________________________ 
    
     EXAMPLE 4 
     Colostrum obtained on the first day after the birth of a pregnant cow in a manner similar to that followed in Example 3 was orally administered every morning to seven 6-month to 5-year old children at a daily dosage of 20 ml for 15 to 30 days. As a control, seven other children were orally administered similarly with the colostrum obtained on the first day after the birth of a pregnant, unimmunized Holstein cow. 
     All of seven children administered with the colostrum of the unimmunized Holstein cow were affected by infantile acute gastroenteritis. On the other hand, of seven children administered with immunized colostrum, only one was affected by infantile acute gastroenteritis. 
     As apparent from the above experiment, a preventive therapeutic agent for infantile acute gastroenteritis of the present invention is effective to prevent such infantile acute gastroenteritis by its oral administration. 
     Having now fully described the invention, it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit of the invention as set forth herein.