Title of Invention

"A METHOD FOR PREPARING AN IMPROVED MALE CONTRACEPTIVE FORMULATION"

Abstract

The present invention relates to an improved contraceptive formulation, and the method of preparation and use thereof. The improved contraceptive formulation consists essentially of a magnetic compound, preferably of an oxide of iron having particles of microsize, which is added to other reactants of the contraceptive during its preparation. The said contraceptive is preferably taken in a solvent, which in turn preferably is dimethyl sulphoxide and injected into the lumen of the vas deferens. The improved contraceptive is detectable externally by non-invasive techniques through-out its stay in the body and can be evacuated to result in the restoration of the fertility.

Full Text

The present invention relates to a method for preparing an improved male contraceptive formulation. Particularly, this invention relates to a method for preparing an improved male contraceptive formulation essentially comprising of magnetic compound, preferably of an oxide of iron having microsized particles. More particularly, the present invention relates to an improved contraceptive formulation as stated hereinabove, which can be detected externally and evacuated to restore the fertility. BACKGROUND The fertility, particularly in males, can be controlled by affecting the flow of the spermatozoa or the quality of the spermatozoa, when they pass through the reproductive duct, called the was deferens, of the ipale. The flow of the spermatozoa can be affected by cutting and tying the vas deferens. This technique is widely used and called vasectomy. As a result of this technique the spermatozoa are prevented from flowing in the forward direction and are accufnulated in the epididymis. The accumulation of the spermatozoa results in production of enhanced antibodies, which in turn destroy the accumulated spermatozoa. The major disadvantage of the known vasectomy technique is that the reversal of the fertility is not effective. The rejoining of the vas deferens does not result in the desired fertility, because the level of generation of antibodies remains high, which in turn continue to destroy the spermatozoa. Further disadvantage of the vasectotny. as known in the art. is the requirement of micro-surgery. The ariother known method to affect the flow of the spermatozoa is the occlusion method. Such known methods comprises of implantation of a reversible occlusion device, which on implantation blocks the flow of the spermatozoa in the vas deferens and control the fertility. This method also has disadvantages, such as, the implanted device has the regulator knob, which stays outside the vas deferens, but within the scrotum and is operated only by the trained medical assistant. In addition this method also has the disadvantages of requirement of surgejy and maintaining the higher level of generation of antibodies even after the removal of the implanted device, which inturns continue to destroy the spermatozoa and resulting in poor level of fertility. Still another disadvantage of this method is the imperfect blockage, which will result in the flow of the spermatozoa and hence the complete destruction of the spermatozoa is not resulted. The another known occlusion method comprises "of injecting polyurethane at a high pressure in the vas deferens. The injected polymer is further polymerized in-situ to a solid plug by introducing an initiator. The solid plug thus formed blocks the flow of the spermatozoa in the manner as described herein above. The major disadvantage of such known occlusion methods is the generation of the back pressure in the epididymis. The quality of the spermato/oa is affected by injecting the injectable contraceptive into the lumen of the vas deferens. The vas deferens is known to be the suitable site for the contraceptive intervention in the males. The disadvantage of such known methods is that the extent of flow and the rate of flow cannot be controlled externally satisfactorily. The main disadvantage, in addition to the disadvantages as described herein above, of the known methods of the prior art for controlling the fertility of males, as described herein above, is that they cannot be detected externally. The basic compound of the contraceptive being a polymer is generally not radio-opaque and hence cannot be detected by X-ray imaging. The magnetic resonance imaging also fails to detect the contraceptive mainly due to its poor contrast with the soft tissue. The ultrasound is also incapable of detecting the contraceptive, due to the low percentage of the basic compound. To overcome this disadvantage, if the net percentage of the basic compound is increased, it will have the disadvantages associated with the higher percentage. Furthermore, some of the regions of the vas deferens are so placed that the ultrasonic approach is not practicable. Still another disadvantage of the known methods of controlling the fertility of males by injectable contraceptives, is that, thejestoralion of the fertility generally calls for an invasive procedure wherein a flushing compound is injected into lumen of the vas deferens, which affects the restoration of the fertility. It is further a disadvantage of the known methods of controlling the fertility. particularly of the vasectomy, that the fertility is not controlled immediately that is contraceptive and the contraceptive technique is not effective from the day one. Therefore, there is a need to have a contraceptive, which can disadvantages of the prior art as described herein above and particularly can be detected externally and evacuated conveniently without the requirement of any surgical procedure. Further, the fertility is restored fully on evacuation of the contraceptive. This is the main object of this invention to make a complete, disclosure of an improved contraceptive formulation, and the method of preparation and use thereof, which can overcome the disadvantages of the prior art as described herein above. Another object of the present invention is to propose for an improved contraceptive formulation, as stated herein above, which can be detected externally by any non-invasive technique, such as, X-rays, magnetic resonance imaging, ultrasound etc. Further an object of this invention is to propose for an improved contraceptive formulation, as stated herein above, which can be evacuated conveniently without the requirement of any surgical procedure. Further, the evacuation oi" the proposed contraceptive results in restoration of the fertility fully. Still another object of the present invention is for an improved contraceptive formulation, as stated herein above, of which the flow extent and the flow rate can be controlled conveniently. Still further an object of this invention is to propose an improved contraceptive formulation, as stated herein above and described herein below, which can control the fertility immediately from the day one, that is from the day the proposed contraceptive is injected. In my Indian Patent No 183196, a process for preparing a process for preparing a contraceptive for use by male is disclosed. SUMMARY Accordingly, this invention provides a method for preparing an improved male contraceptive formulation comprising mixing 35-55 % by weight of polymer/ copolymer such as herein described, 5-25 % by weight of magnetic compound such as herein described and 20-60 % by weight of solvent such as herein described to obtain the improved contraceptive formulation. Said polymer/copolymer is a copolymer of the styrene maleic anhydride or acrylic acid comethylmethacrylate or acrylic acid cobutylacrylate or maleic anhydride comethylmethacrylate or itatonic acid comethylmethacrylate or polyacrylic acid or hydroxyethyl methacrylate or polymemylmehtacrylate, preferably a copolymer of siyrene maleic anhydride. The molecular weight of the copolymer is between 55000 to 100000, preferably between 85000 to 93000. Said solvent is dimethyl sulfoxide or sodium bicarbonate, preferably dimethyl sulfoxide. Said magnetic compound is an oxide of the magnetic metal, preferably an iron oxide and more preferably ferric oxide. Said magnetic compound has the microsized particles, preferably between 1 to 20 micron, more preferably between 4 to 10 micron. Said formulation comprises between 8 to 15 % by weight of overall composition of said magnetic compound. According to the preferred embodiment of the present invention the injectable basic compound of the presently disclosed improved contraceptive formulation, as stated herein above, is selected from the group of polymers or the copolymers and the solvent is selected from the group of solvents having the better tissue penetration into the folds of the inner wall of the vas deferens and capable of helping in the retention of the selected polymer or the copolymer. The magnetic compound is preferably an oxide of the magnetic metal. •• The specific composition range of the selected copolymer or polymer is selected to have the desired viscosity and the flow characteristics and the molecular weight, so that the copolymer or the polymer can not function merely as an occlusion device and hence having negligible positive charge. Similarly on the other end it cannot have excessive charge with the reduced stability but have a better biological effects. Such as, it should not have the free flowing property, which in turn may be responsible lor the How of the copolymer or the polymer to the vennontenum, "which is the sensitive member and the copolymer or the polymer may cause the irritation, and the injecting of the proposed contraceptive should not become difficult. However, the present invention is not restricted to the method of preparation of and to the selection of the copolymer or the polymer. For the example, without (lie intention to limit the scope of the present invention, the copolymer or the polymer, preferably may have relative viscosity between 1.2 to 2.5 and molecular weight between 55,000 to 1,00,000 . The pH of the copolymer or the polymer on in-situ hydrolysis is preferably between 4 .0 to 4 .5. The magnetic compound is preferably taken in powder form. The particle size of the powder form of the magnetic compound is preferable microsize. particularly between 1 to 20 micron, more particularly between 4 to 10 micron. The presently disclosed contraceptive formulation can be prepared by using the active polymer, such as copolymer of styrene maleic anhydride or the passive polymer, such as polyurethane followed by addition of the initiator to further polymerise the polyurethane. The major difference for selecting the active polymer or the passive polymer is the requirement of the clinician to have the flowing injectable contraceptive which can also, affect the fertility ability of the spermalozoa, which can be met by using the active polymer, or the requirement of the clinician is to have a contraceptive capable of forming the plug or blockage to prevent UK: (low of the spermatozoa, which on-turn can be met by using the passive polymer. The contraceptive can also incorporate the polymer base, which can hydrolyze in the spermatic fluid and/or can develop a positive charge and may result in the decrease of pl-l in-situ. The performance of the contraceptive formulation prepared in accordance to the preferred embodiment of this invention essentially comprisini1. ol the magnetic compound will not be affected. However, the use of presently disclosed formulation is suitable with both the polymers, i.e. active and passive polymer. The range of viscosity, flow characteristics, molecular weight and of pH are to suggest the preferable values of these properties of the selected polymer, which does not mean that the use of the presently disclosed formulation of the contraceptive will alter the said - properties of the selected polymer. On the other end the solvent carrier of the contraceptive may incorporate the reactive moiety, such as sulphur. According to one of the preferred embodiment of the present invention, contraceptive formulation when prepared in accordance to the present invention, comprising of copolymer of styrene maleic anhydride, dimethyl sulphoxide and the iron oxide results in the formation of the styrene maleic anhydride-dimethyl sulphoxide complex, which in-turn is injected in the-vas deference. This complex in-turn enters in the folds of the vas deferens inner wall which promotes the anchorage and retention of the contraceptive. The complex breaks only when the reaction is complete. The dimethyl sulphoxide gets absorbed into the surrounding tissue and the blood stream for ultimate excretion. The presently disclosed formulation incorporating the magnetic compound facilitates the detection of the pathway of the excretion in addition to the detection of the location and movement of the protein (of spermatic fluid) -polymer complex, particularly the polar amino acid-styrene maleic anhydride copolymer complex, which was formed before the "breakage of the styrene maleic anhydride copolymcr-dimethyl sulphoxide complex. The protein-polymer complex has positive charge and the protein layer around the copolymer in this complex protects the dissolution of the copolymer. which in turn definelly has the advantage of long - term retention and effective action of the contraceptive in the vas deferens and as well as of its long term detection. The contraceptive as described herein above can also be converted to give the performance as occlusion device by forming the plug to block the flow of the spermatozoa. This action is achieved by increasing the percentage of the basic polymer with respect to the solvent, that is, by increasing the percentage of the styrene maleic anhydride copolymer with reference to dimethyl sulphoxide. The protein-copolymer complex, as stated herein above, can be broken by injecting the extra dose of the solvent, particularly of the dimethyl sulphoxide or sodium bicarbonate, which in-turn breaks the protein-copolymer complex and allows the removal of the contraceptive. This reaction of breaking the protein-copolymer complex definitely has the advantage of reversibility of the proposed contraceptive. However, the present invention is described by way of the foregoing example without any intention to restrict the scope of this invention. EXAMPLE In accordance with the present invention the basic copolymer is prepared by -copolymerising styrene and maleic anhydride monomers in ethyl acetate in the nitrogen atmosphere and subjected to a step of irradiation at a dose of 0.2 megarad for every 40 grams of the polymer and a dose rate of 30 to 40 rad/sec. Preferably the dose is 0.22 megarad and at a dose rate of 30 rad/sec. The source of irradiation is cobalt 60 gamma radiation. This step is followed by addition of ether to precipitate the copolymer and to wash with hot water to remove the traces of the unreacted homopolymers and maleic anhydride monomer. The copolymer is aired and dissolved in 1,2 dichloro-ethane for removal of styrene monomer by soxhlet extraction. The polymeric solution is filtered to remove the styrene monomer and the polymer is precipitated again from this solution by the addition of ether. The precipitated polymer is again washed with hot water, dried and stored. The molecular weight of the copolymer thus formed is between 55000 to 100000, preferably between 85000 to 93000, having relative viscosity between 1.2 to 2.4, preferably between 1.3 to 2.0. The selected quantity of the polymer thus prepared is dissolved in the selected quantity of the pure solvent to which the selected quantity of the magnetic compound is added. The selected quantity as referred herein means the quantity as stated herein above. The formulation is made homogenised and has the advantage of providing uniform distribution after the injection. The magnetic compound, as stated herein above, is an oxide of a magnetic metal, preferabaly of iron, more preferably it is an iron oxide having composition of Fe304. - The magnetic compound is preferably taken in powder form having the microsize particles, particularly between 1 to 20 micron, more particularly between 4 to 10 micron. The proposed improved contraceptive formulation comprises essentially of 5 to 25% by weight of the magnetic compound, preferably between 8 to 15% by weight of the magnetic compound. In accordance to one of the preferred embodiments of this invention the proposed contraceptive is first injected only in the vas deferens by an incision in the scrotal skin or by a per-cutaneous method. According to preferred embodiment of this invention the proposed contraceptive is injected into vas deferens only in the complex form comprising of complex of copolymer/polymer-solvent complex and magnetic compound. The proposed contraceptive will result in the fertility control immediately from the day it is injected. If-the fertility control is-desired for a certain period of time the dose of the proposed contraceptive is selected so that the injected contraceptive itself develops the free flowing property on expiry of the non-fertility period, as the presently disclosed contraceptive is effective from the day it is injected into the vas deferens. However, the presently disclosed contraceptive can also be injected into vas deferens by any such known method of the art. The magnetic compound defmetly has the advantage of overcoming the disadvantages of the known such contraceptive formulations. The flow of the contraceptive after injection can be controlled by applying the magnetic field, which inturn generates the drag force on the contraceptive comprising the magnetic compound and this result in control of the flow of the contraceptive. The contraceptive prepared in accordance to the presently invention, comprising of the magnetic compound produces the magnetic field, which can be sensed on the body surface, which in-turn offers an advantage of detection of the proposed contraceptive externally and without employing any invasive technique. In case the magnetic field intensity of the magnetic compound of the proposed contraceptive formulation reduces over a period of time, the same can he improved by magnetising the contraceptive of the present invention internally by applying an external magnetised field. This remagnetisation process, that is application of the external magnetising Held, will not result in any remagnenl magnetic Held on the body surface, thus will not have adverse effect to the subject but will have an advantage of permitting the detection of the injected contraceptive even for a longer time. The injected contraceptive can be set to the circular, spiral and rotation movements by applying the rotating magnetic field externally. This circulation, spiral and rotational movement as a result of the application of the external rotational magnetic field produces the churning action and the protein-polymer complex, formed after injecting the contraceptive as stated herein above, or the matrix of the injected polymeric contraceptive also gets churned and the big flakes formed of the contraceptive gets fragmented, which inturn leads to the evacuation of the injected contraceptive even after the complex has been formed. The evacuation will lead to the restoration of the fertility and gives an advantage of the reversibility of the proposed contraceptive, which again is acheived without employing any invasive technique. .. It is understood from the foregoing description that the proposed contraceptive formulation comprising of the magnetic compound as one of the essential component results in convenient means of detecting the presence of the injected contraceptive and the movement of the same, that is to have the advantage of the static and the dynamic detection without exposing the body to any harmful energies. In addition it helps to control externally the flow path and the flow rate of the injected contraceptive and "as well as. convenient evacuation without employing any invasive technique, thus avoiding any trauma to the patient. 1 CLAIM :- 1. A method for preparing an improved male contraceptive formulation comprising mixing 35-55 % by weight of polymer/ copolymer such as herein described, 5-25 % by weight of magnetic compound such as herein described and 20-60 % by weight of solvent such as herein described to obtain the improved contraceptive formulation 2 A method as claimed in claim 1 wherein said polymer/copolymer is a copolymer of the styrene maleic anhydride or acrylic acid comethylmethacrylate or acrylic acid cobutylacrylate or maleic anhydride comethylmethacrylate or itatonic acid comethylmethacrylate or polyacrylic acid or hydroxyethyl methacrylate or polymethylmehtacrylate. 3. A method as claimed in claim 2 wherein said copolymer is a copolymer of styrene maleic anhydride. 4. A method as claimed in any of the preceding claims wherein the molecular weight of the copolymer is between 55000 to 100000, preferably between 85000 to 93000. 5. A method as claimed in claim 1 wherein said solvent is dimethyl sulfoxide or sodium bicarbonate. 6. A method as claimed in claim 1 wherein, said magnetic compound is an oxide of a magnetic metal. 7. A method as claimed in claim 6 wherein said magnetic compound is an iron oxide 3. A method as claimed in claim 7 wherein said iron oxide is of ferric oxide. 9. A method as claimed in claims 1 and 6 to 8, wherein the said magnetic compound has the microsized particles, preferably between 1 to 20 micron, more preferably between 4 to 10 micron. 10. A method as claimed in claims 1,6 to 9, wherein the said formulation comprises between 8 to 15 % by weight of overall composition of said magnetic compound. 11. A method for preparing an improved male contraceptive formulation substantially described and illustrated herein above.

Documents:

716-del-1996-abstract.pdf

716-del-1996-claims.pdf

716-del-1996-complete specification (granted).pdf

716-del-1996-correspondence-others.pdf

716-del-1996-correspondence-po.pdf

716-del-1996-description(complete).pdf

716-del-1996-description(provisional).pdf

716-del-1996-form-1.pdf

716-del-1996-form-13.pdf

716-del-1996-form-19.pdf

716-del-1996-form-2.pdf

716-del-1996-form-4.pdf

716-del-1996-form-5.pdf

716-del-1996-form-6.pdf

716-del-1996-form-9.pdf

716-del-1996-pa.pdf

716-del-1996-petition-others.pdf