CA1189789A - Sterilization process for mammals - Google Patents

Sterilization process for mammals

Info

Publication number
CA1189789A
CA1189789A CA000322706A CA322706A CA1189789A CA 1189789 A CA1189789 A CA 1189789A CA 000322706 A CA000322706 A CA 000322706A CA 322706 A CA322706 A CA 322706A CA 1189789 A CA1189789 A CA 1189789A
Authority
CA
Canada
Prior art keywords
composition
mammalian species
injection
bacillus
guerin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000322706A
Other languages
French (fr)
Inventor
Gursaran P. Talwar
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
All India Institute of Medical Sciences AIIMS
Original Assignee
All India Institute of Medical Sciences AIIMS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by All India Institute of Medical Sciences AIIMS filed Critical All India Institute of Medical Sciences AIIMS
Priority to CA000322706A priority Critical patent/CA1189789A/en
Priority to DE2923333A priority patent/DE2923333C2/en
Priority to GB7920917A priority patent/GB2042889B/en
Priority to FR7924868A priority patent/FR2487200A1/en
Priority to IT19567/80A priority patent/IT1205229B/en
Application granted granted Critical
Publication of CA1189789A publication Critical patent/CA1189789A/en
Expired legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/04Mycobacterium, e.g. Mycobacterium tuberculosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66Microorganisms or materials therefrom
    • A61K35/74Bacteria

Abstract

STERILIZATION PROCESS FOR MAMMALS
ABSTRACT OF THE DISCLOSURE

Aspermatogenesis is achieved in mammalian species without disturbance of libido and hormone level by intra-testicular injection of Bacillus of Calmette and Guerin.
The procedure is applicable to a wide variety of mammalian species.

Description

MIS~6 STERILIZATION PROCESS FOR MAMMALS
The present invention is directed to sterilization of mammalian species.
Sterllization of male animals, practised to limit reproduction in stray anlmals and livestock, is usually effected by castration. Sterilization operations involving vasectomy and vasligation and also effected on male humans.
The extreme nature of these procedures and the necessity for skilled surgical operation has led to suggestions of alternative approaches to mammalian sterilization. For example, a number of hormonal formulations, consisting of anti-androgens and androgens, have been suggested for suppression of spermatogenesls or interfering with the maturation of sperm.
In early clinical trials, these formulations, however, have exhibited adverse side effects, including, loss of libido and a dependence on a continual intake of hormonal steroids.
The present invention enables aspermatogenesis to be achieved in mammalian species without disturbance of libido and hormone levels. The invention avoids the necessity for surgical operation, provides a humane approach to the sterilization of males and the procedure may be effected by semi skilled personnel.
In the present invention, Bacillus of Calmette and Guerin (BCG) is intra-testicularly injected in an amount at least effective to achieve aspermatogenesis.
Accordingly, in one embodiment, the present invention provides a sterilizing composition for the sterilization of male mammalian species by intratesticular injection, comprising the Bacillus of Calmette and Guerin and an aqueous carrier therefor.
In another embodiment, the invention provides a composition for sterilizing mammalian species, comprising the Bacillus of Galmette and Guerin formulated for intra-testicular in~ection to provide a .Yi`,~

37~
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concentration of at least 1.5 x ]07 organisms per testicle.
BCG is widely known and is used as a vaccine in human and other animals for protection against tuberculosis. It has never been suggested, heretofore, as far as we are aware, that i-t is possible to achieve aspermatogenesis by intra-testicular injection of BCG
into male animalsO The novel utility of BCG for aspermatogenesis is entirely unexpected, havlng reyard to the known utility and properties of BCG.
While we do not wish to be bound by any theory as to the manner in which the BCG produces aspermatogenesis in this invention, there are indications in the tests we have conducted that the BCG
creates, within the testicle, an inflammatory response which brings to local sites the cells competent for eliciting immune response. The immune response is generated selectively against the antigens present on spermacytes and the intermediate developing stages of spermatozoa, so that spermatogenesis is blocked.
The method has been found to be effective against a]l species tested, including such widely-different species as rats, guinea pigs, rabbits, dogs, rams, bucks and rhesus monkeys. Preliminary testing also demonstrates the effectiveness and utility of the procedure in blocking spermatogenesis in humans.
No adverse side ef~ects to the treatment were observed. In all the test cases, the animals retained their libido, and blood androgen levels were unchanged by the procedure. Histological observations also showed the normalcy of Sertoli and Leydig cells, the latter being confirmed by a rise in plasma androgen levels after administration of gonadotropins.
In addition, no apparent toxicity was observed, no decline in animal body weight or other sign of morbidity were observed, and blood chemistry remained normal, indicating the normalcy of endocrine, organ and metabolic functions.
, .
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The present invention has considerable practical signif:Lcance both with respect to control of reproduction of stray animals and livestoc~ and with respect to human population control. The bacillus is widely available and relatively inexpensive, so that large scale implementation may be practical.
The apparent absence of any adverse side effects, especially the problematical side effects of loss of libido and androgens inherent in prior procedures, renders the procedure especially advantageous.
The dosage used in the intra-testicular injection is at least the quantity effective to achieve aspermatogenesis, and usually is well in excess of that minimum level. The minimum quantity used varies depending on ~he species requiring sterili~ation. The ~uantity of BCG used generally is at least about 3 times the normal human dose for anti-tuberculosis injections, or at least about 1.5 x 107 organisms.
Quantities in excess of 1000 times the human dose (5 x 101 organisms) generally do not produce any added benefit, although may be used, if desired. The injection is effective in a short period of time, generally less than 30 days.
The invention is i]lustrated in the following Examples:
Example I~
Samples of BCG vaccine, consisting of quantities of lyophilized live bacilli from 7 to 110 times the human dose (0.35 to 5.5 mg, 3.5 x 10 to 55 x 108 organisms) suspended in increasing quantities of saline solution (0.15 wt~ MaCl in water) from 0.05 ml to 0.3 ml, were injected into each testicle of a number of adult male dogs weighing between 13 kg and ~0 kg.
Doses greater than 14.0 mg/testicle were found to have no additional or faster effect. Sterilization, as determined by ejaculation of sperm-free semen, occurred in 21 to 30 days post injection.
- There were no side-effects as evidenced by determination of the following parameters:

(a~ Body weight constant ~or up to L0 monthc;.
(b) Libido intact for ~t least 10 months.
(c) Semen volume essentially unchanged.
(d) Plasma testerone and cortisol essentially normal.
(e) Haemotology, including haemoglobin, haemotocrit and leucocyte count unaltered.
(f) Liver functions, including bilirubin, ALP, SGPT
and I,DH, were unaltered.
(g) Kidney functions such as blood urea and serum creatinine were unchanged.
(h) Other metabolic ~unctions that were monitored and found to be unchanged were, blood glucose, serum cholesterol, total serum proteins, serum albumin and serum globulins.
Example II - Rams Three rams were given 1,0~3 x normal human dose of BCG (about 50 x 10 organisms) in each testicle. Semen samples showed that after a maximum of four weeks there were no viable sperm remaining. Three control rams who were kept in the same area and uninjected showed no change in sperm count or motility.
~xample III - Non-human Primates Two male monkeys were injected with BCG vaccine (50 to 100 x normal human dose, 2.5 to 5 mg, 2.5 x 109 to 5 x 10 organisms) in each testicle. Monitoring of metabolic functions showed that the monkeys remained perfectly healthy. Histological examination on biopsy showed that spermatogenesis has ceased.
_xample IV ~ Other Species A number of other species were treated with BCG
vaccine in doses varying from 3 to l,000 times the normal human dose. These included rats, guinea pigs and rabbits. In all cases metabolic functions were unchanged and histological examination of biopsy specimens showed that spermatogenesis had ceased. The average dose was 10 times the normal human dose.
In summary of this disclosure, the present invention is directed to a sterilization procedure which involves an entirely unexpected use of BCG.
, ~ a~
~a Modiflcaticns are possible within the scope of the inven-tion.

Claims (6)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
1. A sterilizing composition for the sterilization of male mammalian species by intratesticular injection, comprising the Bacillus of Calmette and Guerin and an aqueous carrier therefor.
2. The composition of claim 1, wherein the mammalian species is selected from the group consisting of rams, non-human primates, rats, guinea pigs or rabbits.
3. The composition of claim 1, wherein the mammalian species is dogs.
4. The composition of claim 1 in the form of an injection dose of at least 1.5 x 107 organisms per testicle.
5. A composition for sterilizing mammalian species comprising the Bacillus of Calmette and Guerin formulated for intra-testicular injection to provide a concentration of at least 1.5 x 107 organisms per testicle.
6. The composition of claim 5 in the form of a suspen-sion in a saline composition containing from 1.5 x 107 to 5 x 1010 organisms per unit dose.
CA000322706A 1979-03-02 1979-03-02 Sterilization process for mammals Expired CA1189789A (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CA000322706A CA1189789A (en) 1979-03-02 1979-03-02 Sterilization process for mammals
DE2923333A DE2923333C2 (en) 1979-03-02 1979-06-08 Sterilization of mammals
GB7920917A GB2042889B (en) 1979-03-02 1979-06-15 Sterilizing male mammals with bcg
FR7924868A FR2487200A1 (en) 1979-03-02 1979-10-05 COMPOSITION FOR STERILIZING MALE MAMMALS WITH CALMETTE AND GUERIN BACILLES
IT19567/80A IT1205229B (en) 1979-03-02 1980-01-30 PROCESS FOR STERILIZATION OF MAMMALS

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CA000322706A CA1189789A (en) 1979-03-02 1979-03-02 Sterilization process for mammals

Publications (1)

Publication Number Publication Date
CA1189789A true CA1189789A (en) 1985-07-02

Family

ID=4113665

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000322706A Expired CA1189789A (en) 1979-03-02 1979-03-02 Sterilization process for mammals

Country Status (5)

Country Link
CA (1) CA1189789A (en)
DE (1) DE2923333C2 (en)
FR (1) FR2487200A1 (en)
GB (1) GB2042889B (en)
IT (1) IT1205229B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4720507A (en) * 1984-03-05 1988-01-19 University Of Western Ontario Biological contraceptive and contraceptive technique for males
US4780312A (en) * 1985-06-04 1988-10-25 National Institute Of Immunology Birth control vaccine

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3229234C2 (en) * 1979-04-13 1986-06-19 Philips Roxane, Inc., St. Joseph, Mo. Chemical castration

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4720507A (en) * 1984-03-05 1988-01-19 University Of Western Ontario Biological contraceptive and contraceptive technique for males
US4780312A (en) * 1985-06-04 1988-10-25 National Institute Of Immunology Birth control vaccine

Also Published As

Publication number Publication date
IT1205229B (en) 1989-03-15
DE2923333C2 (en) 1986-07-24
FR2487200B1 (en) 1983-06-24
GB2042889A (en) 1980-10-01
IT8019567A0 (en) 1980-01-30
DE2923333A1 (en) 1980-09-11
FR2487200A1 (en) 1982-01-29
GB2042889B (en) 1983-03-09

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