Vaginal preparation for the diagnosis of human female uterotubal patency and function for the purpose of fertilization of gametes

Abstract

A vaginal preparation for the diagnosis of human female uterotubal patency and function, comprising particles having a nucleus absorbable by the tissues of the human body, and a coating for the nucleus which is dissolvable and non-absorbable by the tissues of the human body, inert and innocuous, the nucleus comprising at least one marker that can be released by the human body through an organic fluid, the coating being dissolvable and sensitive, for the purpose of the dissolution thereof, to time and/or changes in pH and/or temperature and/or another chemical/physical parameter along the route from the vaginal area to the tubal and pelvic area, the particles having a size, weight and ovoid shape corresponding approximately to those of spermatozoa.

Claims

1. A vaginal preparation for the diagnosis of human female uterotubal patency and function, characterized in that it comprises particles and a dispersion medium wherein: the particles have: (1) size of 10-60 microns, weight and ovoid shape corresponding approximately to those of human spermatozoa; (2) a nucleus absorbable by the tissues of the human body and comprising at least one marker that can be released by the human body through an organic fluid; and (3) a coating which is dissolvable at pH>6.5, inert and innocuous for the tissues of the human body; and the dispersion medium simulates the human seminal fluid in terms of pH and density and comprises a combination of prostaglandin (PG) f2alpha and prostaglandin E at the concentrations and ratios physiologically present in human seminal fluid, said prostaglandins being able to determine cervical-uterine contraction needed for transporting the particles from the vagina to the outer third of the tube in -5 hour(s).

2. The vaginal preparation according to claim 1, characterized in that said nucleus has a removable vehicle to which said marker is bound.

3. The vaginal preparation according to claim 1, characterized in that said marker is radioactive.

4. The vaginal preparation according to claim 2, wherein said marker is C-13 and said vehicle is urea and can be removed by hydrolytic splitting promoted by said biochemical agent, consisting of urease.

5. The vaginal preparation according to claim 1, characterized in that said marker is colorimetric.

6. A kit for diagnosing human female uterotubal patency and function, characterized in that it comprises: at least one dose of a preparation according to claim 1, wherein said preparation comprises approximately 250 million of the particles suspended in the dispersion medium.

7. The vaginal preparation according to claim 1, wherein a ratio between the particles and the dispersion medium is about 5:95.

8. The kit according to claim 6, characterized in that it further comprises a breath or organic fluid collector and a vaginal pH tester.

9. The vaginal preparation according to claim 1, characterized in that said marker is selected from: Urea-13C, Riboflavin and Vitamin B12.

Description

EXAMPLE 1

(1) The nucleus comprises a radioactive marker bound to a vehicle.

(2) The marker used consists in C-13, already used in gastroenterological tests for diagnosing malabsorption or helicobacter pylori syndromes.

(3) The biodegradable vehicle used for C-13 is urea.

(4) The presupposition, as is well known, is that both pH and temperature change in the tract made up of the vagina-uterus-tube-pelvic cavity, and that in a periovulatory follicular phase uterine contractility is physiologically cervical-fundal in order to transport spermatozoa from the vagina to the outer third of the tubes. This transport is made exploitable thanks to the enhancement of this function produced by the prostaglandins physiologically present in the seminal fluid deposited in the vagina and, in the diagnostic test, by the prostaglandins enriching the particle suspension/release medium of Test Substance 1 and Test Substance 2.

(5) The diagnostic test is performed in the following manner.

(6) Use is made of a kit comprising at least one dose of the preparation (with Test Substance 1 or 2), a breath collector (if Test Substance 1 is used) or a urine collector with an attached colorimetric indicator (in the case of Test Substance 2), a vaginal pH tester, and means for collecting and/or analyzing the breath exhaled from the lungs to detect the presence of C-13.

(7) Initially, the subject to be tested by means of the pH tester, for example litmus paper, evaluates the degree of vaginal acidity. Only if this corresponds to the absence of vaginitis (which can be detected through changes in the acidity of the vaginal environment) will it be possible to proceed with the test.

(8) The subject introduces the product into her vagina, strictly during the advanced follicular phase (between +12th and +14th day of the cycle), and waits for a time ranging from 5 minutes to 24 hours (according to the type of coating, the dissolution of which depends on time, pH, temperature or a combination of more than one of these factors).

(9) If the genital tract is intact in terms of propulsive contractile function and tubal patency, the particles of the preparation will be pushed into the outer third of the tubes or into the pelvic cavity, where, as a result of dissolution, they will lose their coating, which will thus release the nucleus of C-13 and urea.

(10) The nucleus without a protective coating will find the biochemical agent, in particular the enzyme called urease, which will hydrolytically split the urea into ammonia and carbon dioxide, thus finally releasing C-13 (in the case of Test Substance 1).

(11) At this point, the C-13 is freely and rapidly absorbed by tissues, transported into pulmonary circulation and from here to the alveoli in order to be gradually exhaled.

(12) The exhaled breath collected in the specific collector will be examined at this point with the means of analysis, in particular a spectrophotometer.

(13) The presence of C-13 in the breath means that: the particles were properly carried from the vagina to the outer third of the tubes or into the pelvic cavity, as could occur with spermatozoa; the tube is open; the coating found conditions therein to be dissolved; and the radioactive marker was transported accordingly in the breath.

(14) This test result indicates that the subject can seek a pregnancy by spontaneous in vivo fertilization or with the help of assisted conception techniques.

(15) The absence of C-13 in the breath instead means that: the particles were not transported (either because of inadequate uterine contractions or tubal impatency) from the vagina to the outer third of the tubes or into the pelvic cavity where there exist conditions for dissolving the coating; and there exists an obstacle to the union and fertilization of gametes.

(16) This test result indicates that the subject can seek a pregnancy by in vitro fertilization.

EXAMPLE 2

(17) The nucleus comprises a colorimetric marker (Test Substance 2), in particular a vital dye or a substance such as vitamin B12 or Methylene Blue or another inert, innocuous colouring agent capable of taking on a different colour as it passes through environments (for example urine) with different physicochemical properties or of releasing colour when removed from the coating which is dissolvable with changes in pH or temperature.

(18) Use is made of a kit comprising at least one dose of the preparation, a urine collector, a vaginal pH tester, and means of colorimetric urine analysis for detecting the presence of the colorimetric marker.

(19) Initially, the subject to be tested by means of the pH tester, for example litmus paper, evaluates the degree of vaginal acidity. Only if this corresponds to the absence of vaginitis will it be possible to proceed with the test.

(20) The subject introduces the product into her vagina, strictly during the advanced follicular phase (between +12th and +14th day of the cycle), and waits for a time ranging from 5 minutes to 24 hours (according to the type of coating, the dissolution of which depends on time, pH, temperature or a combination of more than one of these factors)

(21) If the genital tract is intact in terms of propulsive contractile function and tubal patency, the particles of the preparation will be pushed into the outer third of the tubes or into the pelvic cavity, where, as a result of dissolution, they will lose their coating, which will thus release the nucleus consisting of the colorimetric marker, which is first absorbed by body tissues and then expelled with urine.

(22) The urine is collected in the specific container and examined using the means of analysis, which can be simply a label applied on the urine container and providing a visual indication of the meaning of the colour found in the collected urine.

(23) The presence of the colorimetric marker in the urine means that: the particles were properly carried from the vagina into the outer third of the tubes or into the pelvic cavity, as could occur with spermatozoa; the tube is open; the coating found conditions therein to be dissolved (change in pH or temperature); and the coloured marker was transported accordingly in the urine.

(24) This test result indicates that the subject can seek a pregnancy by spontaneous in vivo fertilization or with the help of assisted conception techniques (for example IUIintrauterine insemination).

(25) The absence of the colorimetric marker in the urine instead means that: the particles were not transported (either because of inadequate uterine contractions or tubal impatency) from the vagina to the outer third of the tubes or into the pelvic cavity where there exist conditions for dissolving the coating; and there exists an obstacle, which is manifested here with the absence of the colouring agent in the urine and in the woman's biology in that no union of gametes or fertilization takes place.

(26) This test result indicates that the subject can seek a pregnancy by in vitro fertilization.

(27) Advantageously, the test exploits the function of uterine contractility, rather than relying on morphology alone (open and closed tubes).

(28) The test has the ability to diagnose the patency and function of the uterotubal unit, can be performed autonomously in a home environment without the need for hospitalization or the assistance of a doctor or nurse, and is painless and extremely easy to use.

(29) The preparation and kit for the diagnosis of female uterotubal patency and function thus conceived are susceptible of numerous modifications and variants, all falling within the scope of the inventive concept; moreover, all the details may be replaced with technically equivalent elements.