Intraprostatic injection of zinc ions for treatment of inflammatory conditons and benign and malignant tumors of the prostate

A method of treating the prostate by intraprostatic injection of zinc ions in a concentration effective to increase the amount of prostatic antibacterial factor and to inhibit the rate of prostatic growth. The treatment is applied to patients with prostatitis, to patients with benign adenomatous hyperplasia of the prostate after prostatic resection and to patients with early prostatic carcinoma as an alternative to surgery as needed to provide long-term remission. The treatment is also applied prophylactically to prevent the development of prostatitis, particularly in males of advanced age.

EXAMPLE 1 
Thirty-six patients with chronic prostatitis were treated as follows: 
Before therapy, a prostatic smear of expressed prostatic secretion (E.P.S.) 
was taken and examined under a microscope. The results are tabulated in 
Table 4. More than 15 pus cells per high power field of microscope 
(H.P.F.) was considered to be significant. 
TABLE 4 
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Prostatic smear before therapy 
No. of pus cells/H.P.F. 
No. of cases 
% 
______________________________________ 
15-50 9 25 
50-100 15 41.7 
above 100 12 33.3 
Total 36 100 
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Bacteriologic studies 
A urine sample was cultured aerobically on blood agar and Mac Conkey's 
media. No growth of any organism was found in more than two thirds of the 
cases. Escherichia coli was found in 4 out of the 36 cases, while 
enterococci was found in 2 cases. 
TABLE 5 
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Urine culture before therapy 
Organisms No. of cases 
______________________________________ 
No growth (after 48 hours) 
30 
E. coli 4 
Enterococci 2 
Total 36 
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The same organisms were found in the prostatic fluid culture discussed 
below, proving that the source of infection was the prostate. 
Prostatic fluid culture 
The expressed prostatic secretion was also cultured aerobically on blood 
agar. No growth of any organisms was obtained in 15 out of the 36 cases. 
E. coli was found in 11 cases, making it the most common organism found. 
Other gram negative species were also found, but were uncommon as seen in 
the Table 6. Enterococci were found in 5 cases. 
TABLE 6 
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Prostatic fluid culture before therapy 
Organisms No. of cases 
______________________________________ 
No growth (non-bacterial prostatitis) 
15 
E. coli 11 
B. proteus 2 
Enterococci 5 
Staphylococcus aureus 2 
E. coli + pseudomonas pyocyaneous 
1 
Total 36 
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Each patient was then treated as follows: While the patient was in the 
lithotomy position, and without anesthesia or analgesia, the perineum was 
sterilized with 70% alcohol. As described above, a Silverman needle was 
introduced, just lateral to the midline, and was pushed by the right hand, 
guided by the index finger of the left hand in the rectum. When its tip 
was felt inside the prostate, the left index finger was withdrawn from the 
rectum, the glove of the left hand was replaced by a sterile one and the 
stylet of the needle was removed. Then 0.5 ml of sterile hydrous zinc 
sulfate (ZnSO.sub.4 .multidot.7H.sub.2 O), already prepared in a sterile 
disposable syringe, was injected through the needle to inside the 
prostate. The needle was withdrawn. At injection, the patient's reactions 
to injection, e.g., pain, vomiting, collapse, pulse, blood pressure and 
the like were noted. 
Two different concentrations of zinc sulfate were used: 1% ZnSO.sub. 
4.multidot.7H.sub.2 O for 20 patients and 0.1% ZnSO.sub. 
4.multidot.7H.sub.2 O for 16 patients. The stock solution was preserved 
in a refrigerator at 4 degrees C. 
Before the second injection and after one week of intraprostatic injection 
of 0.5 ml zinc sulfate, each patient was interrogated as regards 
subjective symptoms, improvement or increased symptoms and any 
complications and a prostatic smear was taken. The number of leucocytes 
per high power field was found to be normal (less than 15/H.P.E.) in 2 
cases, and the patients symptoms were quite improved. All of the other 
patients showed improvement and the number of pus cells decreased as seen 
in Table 7. No great difference was found between the results of treatment 
with 1% or 0.1% zinc sulfate and hence the two groups were grouped 
together. 
TABLE 7 
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Prostatic smear after first injection 
No. of leucocytes/H.P.E. 
No. of cases 
% 
______________________________________ 
Within normal 2 5.6 
15-50 22 61.1 
50-100 8 22.2 
above 100 4 11 
Total 36 100 
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The second injection was given using the same amount and the same 
concentration of zinc sulfate as the first injection, using the same 
procedure. 
After the second injection of zinc sulfate, most of the patients exhibited 
marked subjective improvement, direct prostatic fluid examination showed 
that the number of leucocytes became within normal in more than half of 
the cases as shown in Table 8. 
TABLE 8 
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Prostatic smear after second injection 
No. of leucocytes/H.P.F. 
No. of cases 
% 
______________________________________ 
Within normal 20 55.5 
15-50 11 30.6 
50-100 5 14 
Total 36 100 
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Before the third injection, 10 ml blood was obtained for estimation of 
serum zinc again after two injections with zinc. Full interrogation with 
the patient was carried cut again and a prostatic smear was obtained and 
examined. The third injection was done using the same concentration, the 
same amount and the same maneuver. 
The patients showing improvement after the first and second injection were 
not given the third injection hence only 34 patients received the third 
injection. 
One week after the third injection more than 50% of patients exhibited 
marked subjective and objective improvement. Their expressed prostatic 
secretions were examined by direct wet preparation and the results are 
tabulated in Table 9. 
TABLE 9 
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Prostatic smear after third injection 
No. of leucocytes/H.P.F. 
No. of cases 
______________________________________ 
Within normal 20 
15-50 14 
______________________________________ 
As shown in Table 10, a correlation is seen in the number of leucocytes in 
prostatic smear before treatment (1), after first injection (2), second 
injection (3) and third injection (4). 
TABLE 10 
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Correlation of number of leucocytes in prostatic 
smears before treatment, after first, second and third 
injections. 
After After After 
No. of Before first second third 
leucocytes/ 
treatment 
injection injection 
injection 
H.P.F. (1) (2) (3) (4) 
______________________________________ 
Within normal 
-- 2 20 20 
(not more than 
15/H.P.F.) 
15-50 9 22 11 14 
50-100 15 8 5 -- 
above 100 12 4 -- -- 
Total 36 36 36 34 
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The third injection is given only to 34 patients because two patients cured 
by previous injection. 
After one month, three months and six months, each patient was examined 
completely. Some patients were followed for one year. A prostatic smear 
was obtained each time and examined by wet film microscopically. Table 11 
shows the results of the follow up. 
TABLE 11 
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Follow up 
Period of follow up 
No. of cases 
______________________________________ 
Three months 15 
Six months 10 
One year 9 
Total 34 
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Results of assessment 
In assessing the results of treatment of chronic prostatitis with 
intraprostatic injection of zinc, twenty-two patients, out of the 36 
cases, had been cured completely (subjective and objective). Eight 
patients exhibited improvement in their symptoms (which is partial 
improvement) with the number of leucocytes in their prostatic secretions 
markedly reduced compared to the pretreatment level. Six cases showed no 
improvement either subjectively or objectively. 
TABLE 12 
______________________________________ 
Results of treatment 
Results No. of cases 
% 
______________________________________ 
Cure (subjective and objective) 
22 61.1 
Improvement 8 22.2 
No improvement 6 16.6 
Total 36 100 
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Prostatic fluid culture after treatment 
The 22 patients who were cured by intraprostatic injection of zinc, 
revealed sterile culture. As regards the eight cases who were improved, 
three of them still had the same organism as before treatment. Also three 
of the six patients who showed no improvement, revealed the same offending 
organisms as beforehand. This is shown in table 13. 
TABLE 13 
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Prostatic fluid culture after treatment 
Organisms No. of cases 
______________________________________ 
No growth 30 
E. coli 2 
B. Proteus 2 
Enterococci 1 
E. Coli + Ps. pyocyaneus 
1 
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This table shows that 9 out of 11 cases infected with E. coli were cured. 
On the other hand pseudomonas pyocyaneus and bacillus proteus organisms 
were insensitive to this type of treatment. Four out of five cases 
infected with Enterococci and the two cases who had Staphylococcus 
infection were also cured by zinc therapy. 
In summary, 15 out of 21 patients with chronic bacterial prostatitis were 
cured and in the group of non bacterial prostatitis 7 out of 15 were cured 
demonstrating that intraprostatic zinc therapy is more effective in the 
treatment of bacterial prostatitis than the non bacterial type. 
The zinc concentration in the serum separated from the blood was determined 
before and after treatment and compared with the zinc concentration in the 
blood drawn from 11 normal persons. Zinc concentration in these samples 
was determined by atomic absorption spectrophotometrically. The results 
were as follows: 
Serum zinc concentration 
The mean serum zinc concentration of the 11 normal subjects was found to be 
84.6.+-.19.8 ug. 
The mean serum zinc in the untreated patients with chronic prostatitis was 
49.2.+-.5.2 ug. This shows that there is hypozincaemia in these patients. 
In addition, the free zinc in these patients was found to be tetrahedral. 
The mean serum zinc after zinc injection was 123.9.+-.24.1 ug demonstrating 
that the zinc level in the serum had been increased. The free zinc in 
these patients was also converted to octahedral. 
EXAMPLE 2 
Zinc acetate and zinc sulfate were administered orally to 24 patients. Zinc 
acetate is characterized by the fact that it is not a gastric irritant but 
both salts are easily soluble in water. 
A solution of zinc acetate was prepared by dissolving 143 mg of zinc 
acetate in 100 ml of clean tap water in a clean container. Zinc sulfate 
was prepared in cachet form, each one containing 100 mg of zinc sulfate. 
The solution of zinc acetate was given to 12 patients in a dose of 15 ml of 
the zinc acetate solution daily for 7 successive days. Hence each patient 
received 105 mg of zinc within this period. 
The zinc sulfate was given to 12 patients in a dose of 100 mg three times a 
day for one week also. 
Clinical assessment: Clinical assessment for every patient before and after 
treatment was performed as mentioned before. 
Examination of prostatic discharge: A prostatic smear was examined for the 
number of leucocytes per high power field of microscope by wet and stained 
film. Culturing of the discharge was carried out and bacterial typing was 
done before treatment with both types of zinc. The results are reported in 
Table 14. 
TABLE 14 
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Prostatic smear before treatment 
No. of leucocytes/H.P.F. 
No. of cases 
______________________________________ 
15-50 10 
50-100 9 
Above 100 5 
Total 24 
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Prostatic fluid culture before therapy 
Culturing the prostatic secretions on blood agar revealed that there was no 
growth of any organisms in half of the cases. E. coli was found in about 
one third of the cases, whereas Klebsiella and Staphylococcus are found in 
4 cases as seen in Table 15. 
TABLE 15 
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Prostatic fluid culture before therapy 
Organisms No. of cases 
______________________________________ 
No growth 12 
E. coli 8 
Klebsiella 2 
Staphylococcus aureus 
2 
Total 24 
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Urine culture 
The urine was cultured on Mac Conkey media revealed that there is no growth 
of organisms in the great majority of cases. E. coli and Enterococci are 
found in some cases as seen in the Table 16. 
TABLE 16 
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Urine culture 
Organisms No. of cases 
______________________________________ 
No growth 19 
E. coli 4 
Enterococci 1 
Total 24 
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Serum zinc: Estimation of serum zinc before treatment by collection and 
separation of serum as mentioned before, was carried out. Also the same 
procedure was repeated for detection of serum zinc after treatment. The 
serum zinc before administration of zinc sulfate and zinc acetate orally 
was found to be 49.2.+-.5.2 ug. After treatment with zinc sulfate, it was 
found to be nearly the same as before treatment but the mean serum zinc 
after treatment with zinc acetate was 123.9.+-.24.1 ug. 
Both groups who were treated with oral zinc sulfate and zinc acetate are 
grouped together, because there was no difference between them, except in 
the serum zinc which was raised in the group treated with zinc acetate. 
Clinically 
There was no improvement, the symptoms and physical findings were nearly 
the same as before treatment. The study of prostatic secretions by wet and 
stained films and the bacteriologic cultures also revealed that there was 
no appreciable changes. 
EXAMPLE 3 
In this study 18 patients with chronic prostatitis were studied. 
The cases were diagnosed by clinical assessment, as well as by examination 
of prostatic fluid by wet and stained films. Also cultures of this 
secretion on aerobic blood agar and antibiogram were made. 
Antibacterial agents: The antibacterial agents used in this group were, 
trimethoprim-sulfamethoxazole (80 mg and 400 mg, respectively), 
cephalosporine, tetracycline and erythromycin. These drugs were given in 
full dosage for 2 weeks accompanied with prostatic massage. 
Prostatic massage: Prostatic massage was done twice weekly for five weeks 
coincidentally with antibacterial agents. The procedure was to massage the 
prostate in the lateral to medial direction, from both sides, then from 
above-downwards. 
Assessments: After treatment, clinical assessment as well as examination of 
prostatic secretion by wet and stained films and also by culture was done. 
Cure was obtained in 5 out of 18 patients. Two cases still had more than 
100 leucocytes/H.P.F. of prostatic secretion compared to three cases 
before treatment. The results are shown in Table 17. 
TABLE 17 
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Leucocytes in prostatic smear 
No. cases No. cases 
No. of leucocytes/H.P.F 
before treatment 
after treatment 
______________________________________ 
Below 15 -- 5 
15-50 8 5 
50-100 7 6 
Above 100 3 2 
Total 18 18 
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Urine culture 
A urine sample was cultured on Mac Conkey's media and sterile urine was 
found in most cases. E. coli was found in 2 cases, Pseudomonas aeroginosa 
in one case and mixed infection by E. coli and enterococci in one case. 
These organism are the same organisms which are found in prostatic 
secretion. 
TABLE 18 
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Urine culture 
Organisms No of cases 
______________________________________ 
No growth 14 
E. coli 2 
Pseudomonas aeroginosa 
1 
E. coli + Enterococci 
1 
Total 18 
______________________________________ 
TABLE 19 
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Bacteriologic culture after treatment 
Type of organisms No. of cases 
______________________________________ 
No growth 12 
E. coli 3 
Enterococci 2 
Pseudomonas aeroginosa 
1 
______________________________________ 
Of these 12 cases with no bacterial growth, 5 cases were cured and added to 
the 7 cases who are originally with no growth. 
The relationship of bacteriologic culture before and after treatment is 
shown in Table 20. 
TABLE 20 
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Correlation of culture before and after treatment 
No. cases No. cases 
Type of organisms 
before treatment 
after treatment 
______________________________________ 
No growth 7 12 
E. coli 6 3 
Enterococci 2 2 
Pseudomonas aeroginosa 
1 1 
Proteus 1 -- 
E. coli + Enterococci 
1 -- 
Total 18 18 
______________________________________ 
Results of treatment. Five cases were cured (subjective and objective) 
where the number of leucocytes reduced to below 15 H.P.F, four cases 
improved (subjective) with a decrease of leucocytes in the prostatic 
secretion (objective), but 9 cases showed no improvement either 
subjectively or objectively. The results are shown in Table 21. 
TABLE 21 
______________________________________ 
Results of treatment 
Results of treatment 
No. of cases 
% 
______________________________________ 
Cured 5 27.8 
Improved 4 22.2 
Not improved 9 50 
______________________________________ 
EXAMPLE 4 
Four patients diagnosed with early prostatic carcinoma (Phase 1) with a 
history of prostatitis were treated as follows: An illuminated endoscope 
with a 50 cm catheter having a needle at one end was inserted through the 
urethra. Progress of the needle was monitored through the endoscope and by 
ultrasonography. The needle was focused towards and inserted into the 
prostate. One ml of an aqueous 6% by weight solution of zinc tannate was 
injected into the prostate through a syringe connected to the opposite end 
of the catheter. 
The patients have been followed for 4 months as of the date of writing and 
have had no increase in the size of the prostate as documented by 
palpation and ultrasonography. All of the patients had difficulty 
urinating before treatment and three out of the four reported that they 
had less difficulty after one month and the fourth after 7 weeks. 
In view of the above, it will be seen that the several objects of the 
invention are achieved and other advantageous results attained. As various 
changes could be made in the above methods without departing from the 
scope of the invention, it is intended that all matter contained in the 
above description or shown in the accompanying drawings shall be 
interpreted as illustrative and not in a limiting sense.