WO2002053168A2 - Sterilising pill - Google Patents

Sterilising pill Download PDF

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Publication number
WO2002053168A2
WO2002053168A2 PCT/DZ2001/000006 DZ0100006W WO02053168A2 WO 2002053168 A2 WO2002053168 A2 WO 2002053168A2 DZ 0100006 W DZ0100006 W DZ 0100006W WO 02053168 A2 WO02053168 A2 WO 02053168A2
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Prior art keywords
pill
women
ovum
sterilising
contraceptive
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PCT/DZ2001/000006
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French (fr)
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WO2002053168A3 (en
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Madani Belhafiane
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Madani Belhafiane
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Priority to AU2002221590A priority Critical patent/AU2002221590A1/en
Publication of WO2002053168A2 publication Critical patent/WO2002053168A2/en
Publication of WO2002053168A3 publication Critical patent/WO2002053168A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0005—Vertebrate antigens
    • A61K39/0006—Contraceptive vaccins; Vaccines against sex hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/18—Feminine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating

Definitions

  • the present project concerns the invention of a new method of sterilization (definitive cessation of procreation) and family planning in women by oral route.
  • This method whose advantages are multiple; it avoids surgical intervention in women which consists in the ligation of the fallopian tubes which is a very traumatic operation.
  • Another advantage of this method concerns family planning and can be used as a method of contraception especially in large multiparous women (women with many children).
  • This sterilization method which is the fruit of several years of research responds to a strong demand for sterilization expressed by women whose medical indications are numerous. Among the other advantages of this method is that it is taken once and does not require continuous treatment, as is the case with oral contraception.
  • the anti-sperm vaccines were the first to be studied. Studies have shown that 5% of sterile men or women develop an immune response against sperm antigens. The presence of anti-sperm antibodies in serum or in secretions from the genital tract is associated with a significant reduction in the pregnancy rate.
  • the principle of this pill is based on a number of phenomena allowing reproduction in the human species.
  • the first stage concerns the ovary which is a genital gland two in number which constitute with the uterus and the fallopian tubes: the internal female reproductive system.
  • the ovary is made up of two parts:
  • An internal, central part where are the vessels which enter the ovary from the hilum, and which forms the medulla.
  • An external part broad and occupies two thirds of the ovary, containing the elements of gametogenesis, and which forms the cortex.
  • Graaf's follicle is made up of an ovum surrounded by numerous follicle cells. The whole is enveloped by a thin blade: the Slavjansky membrane. The cortical cells orient themselves in a particular way to form on the one hand the external theca, on the other hand the internal theca. The internal theca is an endocrine gland. Some follicle cells will undergo a gradual maturing process. The follicular cells increase in size then they are destroyed, except at the periphery, where they will constitute an external base: the granulosa, the latter remains separated from the internal theca by the Slavjansky membrane. The destruction of these follicle cells leads to the formation of a cavity, the anrium which fills with a liquid where the egg bathes.
  • the ovary has a dual role: It releases an egg every month in women from puberty to menopause. He secretes female sex hormones. The Graafian follicle: it secretes folliculin at increasing rates until the twelfth day of a woman's menstrual cycle.
  • Follicular stimulation pituitary hormone or FSH Folliculo-stimulin-pituitary
  • Luteinizing hormone or LH It is necessary for the hormonal secretion of the follicle.
  • the stimulating pituitary hormone or LTH It is assimilated to prolactin, ensures the maintenance of the corpus luteum and the secretion of progesterone.
  • the pituitary gland acts through these hormones on the ovary to ensure the menstrual cycle in women.
  • the ovum will be ready after the maturation of the De Graaf follicle which distends under the effect of a fluid sweating, then there is a bulge on the surface of the ovary which constitutes the stigma: point of emergence of the egg.
  • the egg once released, is collected at the level of the horn of the tube.
  • the ovum has only 24 hours to be fertilized, after ovulation, the ruptured follicle turns into a yellow body.
  • the ovum Cell born from the ovary after maturation of a primordial follicle, which constitutes the female gamete.
  • the primordial follicle comes from the oocyte from the ovogonia, which is the stem cell of the female seminal line, which still has 46 chromosomes.
  • These ovogonies will form with the small germ cells which accompany them the Pfl ⁇ ger cords of the embryonic ovary.
  • the ovogonies At birth, the ovogonies have undergone their reduction mitosis and will become oocytes, which, surrounded by their follicle cells, constitute the primordial follicles.
  • Ovulation according to C. Thibault involves a succession of cytological and metabolic changes. LH and FSH act directly on cumulus cells to dissociate them.
  • the rest of their action is done by steroids and prostaglandins.
  • the steroid surge that follows the peak of gonadotropins is essential for follicular rupture.
  • Three groups of enzymes are involved: collagenases, lyzosomal hydrolases, fibrinolytic enzymes.
  • the ovisac is the site of profound transformations. The wound is closed with a fibrin clot. A vesicle with a pleated and collapsed wall forms, the starting point of the yellow body.
  • the granulosa is invaded by blood capillaries, the first stage of luteinization.
  • the granular cells multiply, hypertrophy, become responsible for characteristic lipid granulations and the content of ascorbic acid increases considerably.
  • the granulosa takes on a pleated appearance. It is later loaded with a characteristic yellow pigment to which it owes its name. At the periphery, the thecal cells retain their activity.
  • the main object of the present invention is the implementation of a sterilization pill which avoids the practice of tubal ligation in women by a surgical procedure deemed too traumatic and expensive.
  • the sterilizing pill can also be safely used as a form of contraception in women.
  • This pill has no side effects except for its sole property that it allows a definitive cessation of procreation in women.
  • This sterilizing pill is the result of an ancestral method used by women in southern France to stop their multiple pregnancies. This method was tested on ten women of childbearing age whose age range was 25 to 39 years, generally housewives. The first preparation of the pill was done in a purely artisanal way; which consisted in the extraction of the complete ovum with its pellucid membrane, with part of the lochia of a woman other than that to be sterilized, they will then be crushed and then added to an excipient which allows the making of the pill.
  • Folliculin it is an ovarian hormone whose physiological role is to trigger the proliferation of the uterine lining before ovulation and which can be obtained synthetically.
  • This pill contains 0.030 mg of folliculin.
  • the excipient which is generally starch.
  • This pill is that of a vaccine: once this pill is taken, thus passing to the level of the general blood circulation, it induces the synthesis of antibodies directed against the main components of the ovum. This synthesis operation can take several months (maximum three months). Once the antibodies are made by the body, they are active and begin their role of destroying the egg once it is ready at the level of the horn of the tube. The permanent presence of these antibodies ensures final sterilization is which is an irreversible process, ie once the woman has been subjected to this method can no longer procreate. The mechanism of action of this pill is identical to that of a vaccine, the expected effect of which is to have an immune reaction. These antibodies is a protein produced by the body in response to the presence of a substance foreign to the body (this substance is called an antigen).
  • the antibodies belong to the globulin fraction of Gamma-globulins.
  • the antibody is specific for the antigen: this substance foreign to the body may be introduced accidentally or for a therapeutic purpose (vaccine antigen) as is the case with this pill.
  • the antibody binds to the antigen which is the ovum and makes it inactive; this is called the antigen-antibody reaction.
  • the primordial sex cells are of endodermal origin: the gonocytes which actively divide by mitosis (cell division) between the 3 rd and 5 th month after fertilization and give rise to ovogonia, the latter separate, surround themselves with some flattened follicle cells.
  • Some ovogonies are clearly at the leptotene stage of meiotic prophase (cell division stage), then after several transformations, these gonocytes become oocytes I, their number is estimated at 1 to 2 million at birth, and there are no more left that around 300,000 oocytes in both ovaries at the age of puberty, all the other oocytes degenerate. It is believed that after some 300 ovulations of a woman during her sex life, there is depletion of the ovum stock, which makes some 600 to 1000 oocytes are involved in each maturation phenomenon leading to ovulation .
  • HCG chorionic gonadotrophic hormone
  • the sterilizing pill which is likely to be used by millions of people, must be developed and produced synthetically.

Abstract

The invention concerns a sterilising pill for definitively stopping female reproductive capability without resorting to surgery through the traumatic experience of tubal ligation and which can be used as a contraceptive method. Said pill consists of a freeze-dried human ovum associated with folliculin and a carrier, the whole assembly is protected by a fine film. Said method consists in taking one single pill on an empty stomach followed by contraception during three successive months by any contraceptive method. The expected result is achieved only as from the third month. Said contraceptive and sterilising method is irreversible owing to the presence of antibodies directed against the ovum. The sterilising pill is designed for women who for some reason or another wish to be sterilised, that is suppress their reproductive capability.

Description

La pilule stérilisante The sterilizing pill
La large gamme des méthodes contraceptives existantes ne répond plus à l'attente de toutes les femmes dont la culture, la religion et le mode de vie sont très variables.The wide range of existing contraceptive methods no longer meets the expectations of all women whose culture, religion and lifestyle are very variable.
Ces méthodes contraceptives dont l'action d'inhibition est dirigée exclusivement sur un organe ou une cellule impliquée dans la reproduction humaine n'échappe pas à des effets adverses variés et de moins en moins acceptés par les femmes et ceci après une longue utilisation. Depuis l'avènement des vaccins, ces derniers n'ont pas cessé de démontrer leur efficacité sur le contrôle des maladies infectieuses ; un tel succès peut être aussi utilisé dans le contrôle de la fertilité.These contraceptive methods, the inhibiting action of which is directed exclusively at an organ or cell involved in human reproduction, is not immune to various adverse effects which are less and less accepted by women after long use. Since the advent of vaccines, the latter have not ceased to demonstrate their effectiveness in the control of infectious diseases; such success can also be used in fertility control.
Le présent projet concerne l'invention d'une nouvelle méthode de stérilisation (arrêt définitif de la procréation) et de planification familiale chez la femme par voie orale. Cette méthode dont les avantages sont multiples; elle évite l'intervention chirurgicale chez la femme qui consiste dans la ligature des trompes qui est une opération très traumatisante. Un autre avantage de cette méthode concerne la planification familiale et peut être utilisé comme un moyen de contraception surtout chez les grandes multipares (femmes ayant beaucoup d'enfants).The present project concerns the invention of a new method of sterilization (definitive cessation of procreation) and family planning in women by oral route. This method whose advantages are multiple; it avoids surgical intervention in women which consists in the ligation of the fallopian tubes which is a very traumatic operation. Another advantage of this method concerns family planning and can be used as a method of contraception especially in large multiparous women (women with many children).
Cette méthode de stérilisation qui est le fruit de plusieurs années de recherche répond à une forte demande de stérilisation exprimée par les femmes dont les indications médicales sont nombreuses. Parmi les autres avantages de cette méthode consiste en sa prise unique et ne nécessite pas un traitement continu comme c'est le cas de la contraception par voie orale.This sterilization method which is the fruit of several years of research responds to a strong demand for sterilization expressed by women whose medical indications are numerous. Among the other advantages of this method is that it is taken once and does not require continuous treatment, as is the case with oral contraception.
En 1974, un premier vaccin anti-hCG a été développé par un groupe de G.P Talwar qui travaillait à l'Institut National d'Immunologie de New Delhi. Ce vaccin était constitué de la sous-unité hCG bêta couplée à l'anatoxine tétanique. Les premiers essais cliniques chez la femme ont été effectués en 1976 dans cinq pays (Inde, Finlande, Suède, Chili et Brésil). Cependant, les taux d'anticorps observés chez le quart des sujets étaient trop faibles pour assurer une protection efficace. En effet, la réponse contre un antigène couplé à une protéine contre laquelle un sujet a été immunisé induit un phénomène dénommé : suppression épi topique et conduit à une faible réponse contre l'antigène. Il apparaissait, alors nécessaire de modifier la composition vaccinale de cette première formulation. C'est à partir de 1986, que l'équipe de G.P Talwar a expérimenté de nouveaux vaccins basés sur la combinaison de chaînes alpha ou bêta d'origine ovine et d'hCG bêta associé à l'anatoxine tétanique et la chaîne bêta de la toxine cholérique comme protéine porteuse.In 1974, a first anti-hCG vaccine was developed by a group of G.P Talwar who worked at the National Institute of Immunology in New Delhi. This vaccine consisted of the hCG beta subunit coupled to tetanus toxoid. The first clinical trials in women were carried out in 1976 in five countries (India, Finland, Sweden, Chile and Brazil). However, the antibody levels observed in a quarter of the subjects were too low to provide effective protection. Indeed, the response against an antigen coupled to a protein against which a subject has been immunized induces a phenomenon called: topical epi suppression and leads to a weak response against the antigen. It therefore appeared necessary to modify the vaccine composition of this first formulation. It was from 1986 that the GP Talwar team experimented with new vaccines based on the combination of alpha or beta chains of ovine origin and hCG beta associated with tetanus toxoid and the beta chain of cholera toxin as a carrier protein.
Des essais ont été effectués en Inde dans trois centres à partir de 1990. En 1992, l'équipe de G.P Talwar rapporte qu'une seule grossesse a été observée sur 750 cycles. Par contre cette approche de G.P Talwar a été critiquée sur la base d'une faible spécificité des immunogènes utilisés. Comme il a été décrit. De plus, la sous-unité alpha d'origine ovine a également une structure proche de l'hCG alpha. Il apparaissait donc nécessaire d'utiliser un immunogène plus spécifique. Une autre équipe de V. Stevens de l'Université de l'Ohio aux USA a développé un vaccin basé sur un peptide synthétique de 37 acides aminés et de structure analogue à l'extrémité carboxyl-terminale de la sous-unité hCG bêta. D'après les résultats préliminaires des essais effectués, ce vaccin était capable d'induire sans effet adverse notable un taux protecteur d'anticorps pendant environ 9 à 10 mois. Si ce vaccin présente une grande spécificité, il pose cependant le problème théorique d'une faible immunogénicité.Trials were carried out in India in three centers from 1990. In 1992, the GP Talwar team reported that only one pregnancy was observed over 750 cycles. However, this GP Talwar approach has been criticized on the basis of the low specificity of the immunogens used. As described. In addition, the alpha subunit of ovine origin also has a structure close to hCG alpha. It therefore appeared necessary to use a more specific immunogen. Another team of V. Stevens from the University of Ohio in the USA has developed a vaccine based on a synthetic peptide of 37 amino acids with a structure analogous to the carboxyl-terminal end of the hCG beta subunit. According to the preliminary results of the trials carried out, this vaccine was able to induce a protective level of antibodies without appreciable adverse effect for approximately 9 to 10 months. If this vaccine has a high specificity, it nevertheless poses the theoretical problem of low immunogenicity.
Parmi les vaccins anti-gamètes, les vaccins anti-spermatozoïde ont été les premiers étudiés. Des études ont démontré que 5% des hommes ou des femmes stériles développent une réponse immune contre les antigènes du sperme. La présence d'anticorps anti-sperme dans le sérum ou dans les sécrétions du tractus génital est associée à une réduction significative du taux de grossesse.Among the anti-gamete vaccines, the anti-sperm vaccines were the first to be studied. Studies have shown that 5% of sterile men or women develop an immune response against sperm antigens. The presence of anti-sperm antibodies in serum or in secretions from the genital tract is associated with a significant reduction in the pregnancy rate.
Le principe de cette pilule repose sur un certain nombre de phénomènes permettant la reproduction chez l'espèce humaine. La première étape concerne l'ovaire qui est une glande génitale au nombre de deux qui constituent avec l'utérus et les trompes : l'appareil génital féminin interne. L'ovaire est formé de deux parties :The principle of this pill is based on a number of phenomena allowing reproduction in the human species. The first stage concerns the ovary which is a genital gland two in number which constitute with the uterus and the fallopian tubes: the internal female reproductive system. The ovary is made up of two parts:
Une partie interne, centrale, où se trouvent les vaisseaux qui pénètrent dans l'ovaire à partir du hile, et qui forme la médullaire. Une partie externe, large et occupe les deux tiers de l'ovaire, contenant les éléments de la gamétogenèse, et qui forme la corticale.An internal, central part, where are the vessels which enter the ovary from the hilum, and which forms the medulla. An external part, broad and occupies two thirds of the ovary, containing the elements of gametogenesis, and which forms the cortex.
Le follicule de Graaf est formé d'un ovule entouré de nombreuses cellules folliculeuses. L'ensemble est enveloppé par une fine lame : la membrane de Slavjansky. Les cellules de la corticale s'orientent de façon particulière pour former d'une part la thèque externe, d'autre part la thèque interne. La thèque interne est une glande endocrine. Certaines cellules folliculeuses vont subir un processus de maturation progressive. Les cellules folliculeuses augmentent de volume puis elles sont détruites, sauf à la périphérie, où elles vont constituer une assise externe : la granulosa, cette dernière reste séparée de la thèque interne par la membrane de Slavjansky. La destruction de ces cellules folliculeuses entraînent la formation d'une cavité, l'antrium qui se remplit d'un liquide où baigne l'ovule.Graaf's follicle is made up of an ovum surrounded by numerous follicle cells. The whole is enveloped by a thin blade: the Slavjansky membrane. The cortical cells orient themselves in a particular way to form on the one hand the external theca, on the other hand the internal theca. The internal theca is an endocrine gland. Some follicle cells will undergo a gradual maturing process. The follicular cells increase in size then they are destroyed, except at the periphery, where they will constitute an external base: the granulosa, the latter remains separated from the internal theca by the Slavjansky membrane. The destruction of these follicle cells leads to the formation of a cavity, the anrium which fills with a liquid where the egg bathes.
Après l'ovulation, il apparaît le corps jaune, en absence de fécondation ce dernier régresse et se transforme en un organe blanc et scléreux : le corpus albicans.After ovulation, the yellow body appears, in the absence of fertilization the latter regresses and turns into a white and sclerotic organ: the corpus albicans.
L'ovaire a un double rôle : Il libère un ovule tous les mois chez la femme de la puberté à la ménopause. II secrète les hormones sexuelles féminines. Le follicule De Graaf : il secrète la folliculine à des taux croissants jusqu'au douzième jour du cycle menstruel de la femme.The ovary has a dual role: It releases an egg every month in women from puberty to menopause. He secretes female sex hormones. The Graafian follicle: it secretes folliculin at increasing rates until the twelfth day of a woman's menstrual cycle.
Le corps jaune secrète la folliculine et la progestérone pendant les douze premiers jours du cycle. Ces sécrétions sont sous le contrôle de l'hypophyse et l'hypothalamus. L'hormone hypophysaire de stimulation folliculaire ou FSH (Folliculo-stimuline-hypophysaire) :The corpus luteum secretes folliculin and progesterone during the first twelve days of the cycle. These secretions are under the control of the pituitary gland and the hypothalamus. Follicular stimulation pituitary hormone or FSH (Folliculo-stimulin-pituitary):
Elle se charge de la croissance du follicule, du développe ment de la granulosa et de la thèque interne.It is responsible for the growth of the follicle, the development of the granulosa and the internal theca.
L'hormone lutéinisante ou LH : Elle est nécessaire à la sécrétion hormonale du follicule. L'hormone hypophysaire stimulante ou LTH : Elle est assimilée à la prolactine, assure le maintien en vie du corps jaune et la sécrétion de la progestérone. L'hypophyse agit par L'intermédiaire de ces hormones sur l'ovaire pour assurer le cycle menstruel chez la femme.Luteinizing hormone or LH: It is necessary for the hormonal secretion of the follicle. The stimulating pituitary hormone or LTH: It is assimilated to prolactin, ensures the maintenance of the corpus luteum and the secretion of progesterone. The pituitary gland acts through these hormones on the ovary to ensure the menstrual cycle in women.
L'ovule sera prêt après la maturation du follicule de De Graaf qui se distend sous l'effet d'une transsudation liquidienne, puis se produit à la surface de l'ovaire un renflement qui constitue le stigma : point d'émergence de l'ovule. L'ovule une fois libéré, est recueilli au niveau du pavillon de la trompe. L'ovule n'a que 24 heures pour être fécondé, après l'ovulation, le follicule une fois rompu se transforme en corps jaune.The ovum will be ready after the maturation of the De Graaf follicle which distends under the effect of a fluid sweating, then there is a bulge on the surface of the ovary which constitutes the stigma: point of emergence of the egg. The egg once released, is collected at the level of the horn of the tube. The ovum has only 24 hours to be fertilized, after ovulation, the ruptured follicle turns into a yellow body.
L'ovule : Cellule née de l'ovaire après maturation d'un follicule primordial, qui constitue le gamète femelle. Le follicule primordial provient de l'ovocyte issu de l'ovogonie, qui est la cellule souche de la lignée séminale féminine possédant encore 46 chromosomes. Ces ovogonies formeront avec les petites cellules germinatives qui les accompagnent les cordons de Pflϋger de l'ovaire embryonnaire. A la naissance, les ovogonies ont subi leur mitose réductionnelle et deviendront des ovocytes, qui, entourés de leurs cellules folliculeuses, constituent les follicules primordiaux. L'ovulation selon C. Thibault met en jeu une succession de changements cytologiques et métaboliques. LH et FSH agissent directement sur les cellules du cumulus pour les dissocier.The ovum: Cell born from the ovary after maturation of a primordial follicle, which constitutes the female gamete. The primordial follicle comes from the oocyte from the ovogonia, which is the stem cell of the female seminal line, which still has 46 chromosomes. These ovogonies will form with the small germ cells which accompany them the Pflϋger cords of the embryonic ovary. At birth, the ovogonies have undergone their reduction mitosis and will become oocytes, which, surrounded by their follicle cells, constitute the primordial follicles. Ovulation according to C. Thibault involves a succession of cytological and metabolic changes. LH and FSH act directly on cumulus cells to dissociate them.
Le reste de leur action se fait par des stéroïdes et les prostaglandines. La poussée des stéroïdes qui suit le pic des gonadotrophines est indispensable à la rupture folliculaire. Trois groupes d'enzymes interviendraient : des collagénases, des hydrolases lyzosomiales, des enzymes fibrinolytiques. Après l'ovulation, l'ovisac est le siège de transformations profondes. La plaie est obturée par un caillot de fibrine. Il se forme une vésicule à paroi plissée et collabée, point de départ du corps jaune. Dans les 24 heures qui suivent, se produit l'invasion de la granulosa par des capillaires sanguins, premier temps de la lutéinisation. Les cellules granuleuses se multiplient, s'hypertrophient, se chargent de granulations lipidiques caractéristiques et la teneur en acide ascorbique augmente de façon considérable. La granulosa prend un aspect plissé. Elle se charge plus tard d'un pigment jaune caractéristique auquel elle doit son nom. A la périphérie, les cellules thécales conservent leur activité.The rest of their action is done by steroids and prostaglandins. The steroid surge that follows the peak of gonadotropins is essential for follicular rupture. Three groups of enzymes are involved: collagenases, lyzosomal hydrolases, fibrinolytic enzymes. After ovulation, the ovisac is the site of profound transformations. The wound is closed with a fibrin clot. A vesicle with a pleated and collapsed wall forms, the starting point of the yellow body. Within 24 hours, the granulosa is invaded by blood capillaries, the first stage of luteinization. The granular cells multiply, hypertrophy, become responsible for characteristic lipid granulations and the content of ascorbic acid increases considerably. The granulosa takes on a pleated appearance. It is later loaded with a characteristic yellow pigment to which it owes its name. At the periphery, the thecal cells retain their activity.
La présente invention a pour but principal la mise en œuvre d'une pilule de stérilisation qui évite la pratique de la ligature des trompes chez la femme par une intervention chirurgicale jugée trop traumatisante et coûteuse.The main object of the present invention is the implementation of a sterilization pill which avoids the practice of tubal ligation in women by a surgical procedure deemed too traumatic and expensive.
La pilule stérilisante peut être aussi utilisée et sans danger comme un moyen de contraception chez la femme. Cette pilule ne présente aucun effet secondaire sauf sa seule propriété qu'elle permet un arrêt définitif de la procréation chez la femme. Cette pilule stérilisante, est issue d'une méthode ancestrale utilisée par les femmes dans le sud algérien pour arrêter leurs grossesses multiples. Cette méthode a été expérimentée sur dix femmes en âge de procréer dont la fourchette d'âge était de 25 à 39 ans, généralement des femmes au foyer. La première préparation de la pilule a été faite d'une façon purement artisanale; qui consistait dans l'extraction de l'ovule complète avec sa membrane pellucide, avec une partie des lochies d'une femme autre que celle à stériliser, ils seront ensuite broyés puis ajoutés à un excipient qui permet la confection de la pilule. Une fois la préparation prête, elle sera prise à jeun par la femme à stériliser (femme présentant une des indications médicales de la stérilisation). Le résultat n'est pas immédiat, il ne sera obtenu qu'après trois mois: c'est à dire le temps nécessaire à l'organisme pour qu'il synthétise les anticorps qui seront dirigés contre l'ovule. Pour attendre cette réponse immunitaire la femme candidate à la stérilisation doit-être protégée contre la grossesse par n'importe quelle méthode contraceptive et ceci pendant au moins trois mois. Une fois ces anticorps sont présents dans l'organisme, ils seront dirigés contre l'ovule, une fois que cette dernière est lâchée par l'ovaire dans le pavillon. Cette méthode une fois adoptée est irréversible c'est à dire que la stérilisation sera définitive. En ce qui concerne la composition de cette pilule et en se reportant aux différentes expériences effectuées, elle est formée de :The sterilizing pill can also be safely used as a form of contraception in women. This pill has no side effects except for its sole property that it allows a definitive cessation of procreation in women. This sterilizing pill is the result of an ancestral method used by women in southern Algeria to stop their multiple pregnancies. This method was tested on ten women of childbearing age whose age range was 25 to 39 years, generally housewives. The first preparation of the pill was done in a purely artisanal way; which consisted in the extraction of the complete ovum with its pellucid membrane, with part of the lochia of a woman other than that to be sterilized, they will then be crushed and then added to an excipient which allows the making of the pill. Once the preparation is ready, it will be taken on an empty stomach by the woman to be sterilized (woman presenting one of the medical indications for sterilization). The result is not immediate, it will only be obtained after three months: that is to say the time necessary for the organism so that it synthesizes the antibodies which will be directed against the ovum. To await this immune response, the female sterilization candidate must be protected against pregnancy by any contraceptive method and this for at least three months. Once these antibodies are present in the body, they will be directed against the ovum, once the latter is released by the ovary in the pavilion. This method once adopted is irreversible, that is to say that sterilization will be final. Regarding the composition of this pill and referring to the different experiments carried out, it is made up of:
Un ovule complet avec sa membrane pellucide lyophilisé. La folliculine : c'est une hormone ovarienne dont le rôle physiologique est de déclencher la prolifération de la muqueuse utérine avant l'ovulation et qui peut-être obtenu d'une façon synthétique. Cette pilule contient 0.030 mg de folliculine. L'excipient qui est généralement de l'amidon. Une fine pellicule de protection.A complete ovum with its lyophilized pellucid membrane. Folliculin: it is an ovarian hormone whose physiological role is to trigger the proliferation of the uterine lining before ovulation and which can be obtained synthetically. This pill contains 0.030 mg of folliculin. The excipient which is generally starch. A thin protective film.
Le principe de cette pilule est celui d'un vaccin : une fois que cette pilule est prise, passant ainsi au niveau de la circulation sanguine générale, elle induit la synthèse d'anticorps dirigés contre les principaux composants de l'ovule. Cette opération de synthèse peut prendre plusieurs mois (maximum trois mois). Une fois que les anticorps sont fabriqués par l'organisme, ils sont actifs et entament leur rôle de destruction de l'ovule une fois que ce dernier est prêt au niveau du pavillon de la trompe. La présence permanente de ces anticorps assure la stérilisation définitive est qui est un processus irréversible, c'est à dire une fois que la femme a été soumise à cette méthode ne peut plus procréer. Le mécanisme d'action de cette pilule est identique à celui d'un vaccin, dont l'effet escompté est d'avoir une réaction immunitaire. Ces anticorps est une protéine élaborée par l'organisme en réaction à la présence d'une substance étrangère à l'organisme (cette substance est nommée antigène).The principle of this pill is that of a vaccine: once this pill is taken, thus passing to the level of the general blood circulation, it induces the synthesis of antibodies directed against the main components of the ovum. This synthesis operation can take several months (maximum three months). Once the antibodies are made by the body, they are active and begin their role of destroying the egg once it is ready at the level of the horn of the tube. The permanent presence of these antibodies ensures final sterilization is which is an irreversible process, ie once the woman has been subjected to this method can no longer procreate. The mechanism of action of this pill is identical to that of a vaccine, the expected effect of which is to have an immune reaction. These antibodies is a protein produced by the body in response to the presence of a substance foreign to the body (this substance is called an antigen).
Les anticorps appartiennent à la fraction globulinique des Gamma-globulines. L'anticorps est spécifique de l'antigène : cette substance étrangère à l'organisme peut-être introduite d'une manière accidentelle ou bien dans un dessein thérapeutique (antigène vaccinal) comme c'est le cas de cette pilule. L'anticorps se fixe sur l'antigène qui est l'ovule et le rend inactif ; c'est ce qu'on appelle la réaction antigène-anticorps.The antibodies belong to the globulin fraction of Gamma-globulins. The antibody is specific for the antigen: this substance foreign to the body may be introduced accidentally or for a therapeutic purpose (vaccine antigen) as is the case with this pill. The antibody binds to the antigen which is the ovum and makes it inactive; this is called the antigen-antibody reaction.
Les cellules sexuelles, primordiales sont d'origine endodermique : les gonocytes qui se divisent activement par mitose (division cellulaire) entre le 3ème et le 5èmβ mois après la fécondation et donnent naissance aux ovogonies, ces dernières se séparent, s'entourent de quelques cellules folliculeuses aplaties. Certaines ovogonies sont clairement au stade leptotène de la prophase méiotique (étape d'une division cellulaire), puis après plusieurs transformations, ces gonocytes deviennent des ovocytes I, leur nombre est estimé à 1 à 2 millions à la naissance, et il ne reste plus qu'environ 300 000 ovocytes dans les deux ovaires à l'âge de la puberté, tous les autres ovocytes dégénèrent. On pense qu'après les quelques 300 ovulations d'une femme au cours de sa vie sexuelle, il y a épuisement du stock d'ovocytes, ce qui fait quelques 600 à 1000 ovocytes sont impliqués dans chaque phénomène de maturation conduisant à l'ovulation.The primordial sex cells are of endodermal origin: the gonocytes which actively divide by mitosis (cell division) between the 3 rd and 5 th month after fertilization and give rise to ovogonia, the latter separate, surround themselves with some flattened follicle cells. Some ovogonies are clearly at the leptotene stage of meiotic prophase (cell division stage), then after several transformations, these gonocytes become oocytes I, their number is estimated at 1 to 2 million at birth, and there are no more left that around 300,000 oocytes in both ovaries at the age of puberty, all the other oocytes degenerate. It is believed that after some 300 ovulations of a woman during her sex life, there is depletion of the ovum stock, which makes some 600 to 1000 oocytes are involved in each maturation phenomenon leading to ovulation .
Plusieurs molécules sont mises en jeu, notamment les protéines de la zone pellucide qui entoure l'ovule, les protéines de la membrane du trophoblaste. Ce trophoblaste secrète une hormone : l'hormone chorionique gonadotrophique (HCG) qui est l'une des cibles de la pilule stérilisante. L'expérience a montré que cette pilule fabriquée à partir d'un lyophilisât d'ovule associé à la folliculine est capable d'induire une réponse immune qui neutralise l'activité biologique et détruit la structure moléculaire de l'ovule et par contre inhibe la fécondation de cette dernière par le spermatozoïde. L'avantage de cette pilule n'échappe pas aux répercussions sur le plan éthique, culturel et religieux des populations, cette pilule présente un intérêt majeur dans le contrôle de la fertilité chez la femme en âge de procréer.Several molecules are involved, notably the proteins of the pellucid zone which surrounds the ovum, the proteins of the trophoblast membrane. This trophoblast secretes a hormone: the chorionic gonadotrophic hormone (HCG) which is one of the targets of the sterilizing pill. Experience has shown that this pill made from an egg lyophilisate associated with folliculin is capable of inducing an immune response which neutralizes biological activity and destroys the molecular structure of the ovum and on the other hand inhibits the fertilization of the latter by the sperm. The advantage of this pill does not escape the repercussions on the ethical, cultural and religious populations, this pill is of major interest in the control of fertility in women of childbearing age.
La pilule stérilisante qui est susceptible d'être utilisée par des millions d'individus, doit être développée et fabriquée d'une façon synthétique.The sterilizing pill, which is likely to be used by millions of people, must be developed and produced synthetically.
Finalement, la réelle volonté des organismes chargés du contrôle de la fertilité à l'échelle internationale et des laboratoires pharmaceutiques doivent être déterminants dans l'élaboration et la promotion de ces produits à visée contraceptive. Dans le domaine de la planification familiale, il est regrettable de constater que des groupes souvent minoritaires ont un rôle délétère sur le développement de nouveaux moyens dont pourrait bénéficier la majorité. Finally, the real will of the bodies responsible for fertility control on an international scale and pharmaceutical laboratories must be decisive in the development and promotion of these contraceptive products. In the area of family planning, it is regrettable to note that often minority groups have a deleterious role in the development of new means from which the majority could benefit.

Claims

Revendicationsclaims
1- Pilule qui permet d'arrêter définitivement la procréation chez la femme, caractérisée par sa composition hormonale en comprimé enveloppé par une membrane protectrice qui protège le principe actif de la pilule contre l'acidité gastrique, passe par la suite dans les intestins où elle libère son principe actif et finalement ce dernier diffuse via la paroi entérale dans la circulation sanguine générale.1- Pill which allows definitively to stop procreation in women, characterized by its hormonal composition in tablet enveloped by a protective membrane which protects the active principle of the pill against gastric acidity, then passes into the intestines where it releases its active ingredient and finally the latter diffuses via the enteral wall into the general blood circulation.
2- Pilule selon la revendication 1 est caractérisée par sa prise unique, facile à prendre, n'exige pas de précautions particulières à prendre et permet la stérilisation définitive de la femme.2- The pill according to claim 1 is characterized by its single intake, easy to take, does not require any special precautions to be taken and allows the final sterilization of the woman.
3- Pilule selon l'une quelconque des revendications précédentes agit comme un vaccin dont l'action est durable et permet à l'organisme de synthétiser des anticorps dirigés contre l'ovule et ses différents constituants.3- Pill according to any one of the preceding claims acts as a vaccine whose action is long-lasting and allows the body to synthesize antibodies directed against the ovum and its various constituents.
4- Pilule selon l'une quelconque des revendications par sa prise unique permet d'éviter chez la femme l'intervention chirurgicale trop traumatisante en vue de la stériliser.4- Pill according to any one of the claims by its single intake makes it possible to avoid in women too traumatic surgical intervention in order to sterilize it.
5- Pilule selon la revendication 4 peut-être utilisée comme méthode contraceptive5- The pill of claim 4 can be used as a contraceptive method
6- Pilule selon l'une quelconque des revendications ne présente aucune contre-indication et ne comporte aucun effet secondaire. 6- Pill according to any one of claims has no contraindication and has no side effects.
PCT/DZ2001/000006 2000-12-31 2001-12-29 Sterilising pill WO2002053168A2 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1312254A (en) * 1968-07-01 1973-04-04 Dow Corning Method for altering the genital function of mammals
WO1996024675A1 (en) * 1995-02-10 1996-08-15 University Of Saskatchewan GnRH-LEUKOTOXIN CHIMERAS
US6103881A (en) * 1989-02-23 2000-08-15 Colorado State University Research Foundation GnRH analogs for destroying gonadotrophs

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1312254A (en) * 1968-07-01 1973-04-04 Dow Corning Method for altering the genital function of mammals
US6103881A (en) * 1989-02-23 2000-08-15 Colorado State University Research Foundation GnRH analogs for destroying gonadotrophs
WO1996024675A1 (en) * 1995-02-10 1996-08-15 University Of Saskatchewan GnRH-LEUKOTOXIN CHIMERAS

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE BIOSIS [en ligne] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1998 KESSEL E.: "Quinacrine sterilization: An assessment of risks for ectopic pregnancy, birth defect and cancer" Database accession no. PREV199900021742 XP002203742 & KESSEL E.: "Quinacrine sterilization: An assessment of risks for ectopic pregnancy, birth defect and cancer" ADVANCES IN CONTRACEPTION, vol. 14, no. 2, 1998, pages 81-90, ISSN: 0267-4874 *
DATABASE CAPLUS [en ligne] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 1997 ZHANG ET AL: "Antibody responses and infertility in mice following oral immunization with attenuated Salmonella typhimurium expressing reconbinant murine ZP3" Database accession no. 1997:26569 XP002203743 & ZHANG ET AL: "Antibody responses and infertility in mice following oral immunization with attenuated Salmonella typhimurium expressing reconbinant murine ZP3" BIOLOGY OF REPRODUCTION, vol. 56, no. 1, 1997, pages 33-41, ISSN: 0006-3363 *
DATABASE MEDLINE [en ligne] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; 1989 TALWAR ET AL: "Anti-fertility vaccines" Database accession no. NLM2665354 XP002203744 cité dans la demande & TALWAR ET AL: "Anti-fertility vaccines" VACCINE, vol. 7, no. 2, 1989, pages 97-101, ISSN: 0264-410X *

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