Method and invention for the treatment of diseases and disorders of the cervix

A method and device for delivering therapeutic agents to the cervix. The method utilizes a diaphragm with an electrically conductive surface that is placed atraumatically over the outer surface and inner os of the mammalian (animal or human) cervix. The agent is delivered to the diaphragm after which the conductive surface of the diaphragm may be charged by a power source to deliver a electrophoretic field to force the agent deep into cervical tissue and cells. The diaphragm may be used with or without the aid of external or internal leads. A unique intrauterine lead designed in this patent may also be used with the diaphragm to enhance delivery of therapeutic agents.

DESCRIPTION OF PREFERRED EMBODIMENTS FIG. 1 : The cervical cup 1 contains an inner layer comprised of an electrically conductive surface that is connected to an insulated wire 2 , which passes atraumatically out of the body and connects to a power source or electroporation device 3 . The inner layer of 1 may also be concomitantly interlaced with a series of channels that ultimately communicate to a tube 4 that passes atraumatically out of the body and ultimately connects to a port 5 and syringe 6 to be used as an injection device for therapeutics in liquid/gel/vapor/gas form. FIG. 2 . The internal lead is charged opposite the cervical cup used in FIG. 1 . 1 is the expandable balloon that has an outer electrically conductive surface that comes in direct adposition to the inner uterine lining when deployed by injecting liquid, gel or air via the syringe 4 traversing through a syringe port 3 that then attaches to a rubber tubing 2 , which ultimately communicates to the intrauterine balloon 1 . A seamless insulated wire 5 connects the conductive surface on 1 to an electroporation device or power supply 6 . FIG. 3 . The same internal lead as described in FIG. 4 , however, the balloon device 1 is deployed upon injection with air/liquid/gel from syringe 4 . Again 3 is the syringe port, 4 is the syringe and 2 is the tube that allows communication of balloon 1 to syringe 4 and also houses an insulated wire 5 which connects the conductive surface on balloon 1 to the power source/electroporation device 6 . FIG. 4 . Intrauterine balloon 1 and cervical cup 2 deployed in a standard therapeutic fashion with the balloon traversing through the inner opening of the cervical cup 2 and the balloon 1 fully inflated. The cup 1 is connected by an insulated atraumatic wire 11 connecting to a power source or electroporation device 10 . Again the inner layer of 2 may also be concomitantly interlaced with a series of channels that ultimately communicate to a tube 3 that passes atraumatically out of the body and ultimately connects to a port 4 and syringe 5 to be used as an injection device for therapeutics in liquid/gel/vapor/gas form. Furthermore connected to the intrauterine balloon is a tube 6 that allows communication with the port 7 and syringe 8 which deploys the balloon. Wire 9 connects conductive surface on balloon 1 with power source or electroporation device 10 . Wire 11 connects conductive surface of cup 1 to negative lead on power source 10 . FIG. 5 . The same instrument set up as in FIG. 4 , however, the apparatus is depicted in vivo and as a vertical section of through the human female reproductive tract with the uterus and cervix as labeled and the fallopian tubes A. Details of numbered objects are the same as described in FIG. 4 . FIG. 6 . A conceptual drawing of device stated in FIG. 5 . For clarity, device is depicted as a cross-sectional representation of the cervical cup minus the wires, tubing, syringe and power source or electroporation device. When the device used in FIG. 5 is triggered to deliver an electrical pulse, it will create electroporation of substances in the direction of the small arrows indicated. The polarity on surfaces of the cervical cup and intrauterine lead may be reversed in polarity, but typically opposite to one another, in order to enhance delivery of positively charged therapeutic agents. FIG. 7 : The same device as in FIG. 1 , however, the inner surface of the cervical cup is composed of two separate electrically conductive surfaces surrounding the inner cylinder 1 and the inner aspect of the outer rim 2 . Surface 1 would be in contact with the endocervical canal, whereas 2 is in direct contact with the outermost lateral aspect of the cervix. Again 3 being an atraumatic insulated wire that connects conductive surface 2 to either an electroporation device or power source 5 . 4 is another insulated atraumatic wire which connects the conductive surface 1 to the same electroporation device or power source 5 , but typically in opposite polarity to conductive surface 2 . Polarities of conductive surfaces 1 and 2 may be switched to suit the direction of electroporation according to the charge of the agent to be delivered. Though not depicted, a tube connecting microfenestrated and embedded channels in any specific region of the cervical cup to a delivery syringe may be fashioned for delivery of therapeutic agents prior to electroporation. Dashed lines in FIG. 7B (top-view) and 7 C (vertical cross-section view) represent electrically conductive surfaces. FIG. 8 . Device in FIG. 7 shown seated in vivo with uterine and cervical tissues as indicated and shaded in medium gray tone. Fallopian tubes are labelled as A. Inner circumference conductive surface in dark gray tone is connected to the negative wire 6 and lead on power supply/electroporation device 7 . Opposing conductive surface in light gray tone is connected by positive wire 5 , which connects to positive lead on same power supply/electroporation device 7 . FIG. 9 . A conceptual drawing of device stated in FIGS. 7 and 8 . For clarity, device is depicted as a cross-sectional representation of the cervical cup minus the wires, tubing, syringe and power source or electroporation device. Conductive surfaces 1 and 2 depicted as dotted lines are directly facing opposite one another and when activated (i.e. electroporation device or power source is triggered to deliver a pulse or current) will create electroporation of substances in the direction of the small arrows indicated. The polarity of surfaces 1 and 2 may be adjusted to suit the charge of the therapeutic agent being introduced into tissue. Embodiments: A further embodiment entails using the proposed inventions for electroporating various agents into a normal or diseased cervix for cervical ripening during prolonged pregnancies, especially in females refractory to conventional therapeutics such as pitocin. Use of the internal intrauterine lead in this circumstance will not be used in conjunction with the cervical cup. Electrical pulses and currents generated from the electroporation device or power source would be tailored for maximal delivery of therapeutic agent with zero to negligible effect(s) on the fetus. In a further embodiment of the invention the cup may be used solely with lipofection and drug agents added and held in place for extended time with any efficient and atraumatic clamp or holder. Moreover greater extended therapy (brachytherapy) may be achieved by creating an internal holder that loops in the internal os and secures the cup snug against the cervix. In a further embodiment one may use the electroporation device without any agent and use the effects of electrical current on the cervix for increasing porosity of the cervix for systemic drugs. As electroporation fields in themselves have also exhibited a bystander effect. The electroporation field in itself may be used to affect cures for various diseases and disorders of the cervix. In yet another embodiment, the distal end of the cervical cup, that traverses through the cervical os and canal, may be fashioned of a resilient and flexible material with memory, that when shrouded in a holder is held in a cylindrical shape. When the central cylinder is advanced through the endocervical canal, the shroud may be released and removed allowing the distal cylinder to fold backwards on itself into the original molded shape enclosing the junction of the inner uterine lining and the beginning of the cervical outlet. This design modification would allow the electroporation of the internal intrauterine outlet leading into the cervical canal. The distal flexible end of the inner cylinder may also be designed to take any form suitable for electroporation of the intrauterine aspect of the cervix. In yet another embodiment the leads depicted in FIGS. 1 and 7 may be reversed in polarity (but still maintaining bipolar configuration) in order to force positively charged substances into cells. Both magnitude and charge of bipolarity between positive and negative leads may be adjusted to increase efficiency of therapeutic agent delivery into cervical tissue. Additionally the negative internal lead may be abandoned all together and multiple external patch leads or shorts with a conductive surface may be used to create tailored electrical fields to focus the direction of electroporation toward specific regions of diseased cervix. In a further embodiment the system may utilize alternate forms of energy transfer in place of electroporation/iontophoresis. These forms include, but are not limited to, phonophoresis and magnetophoresis. In another embodiment the inductive circuit can be designed as a resonant circuit tuned to the radio frequency range (>9 KHz) capable of producing electrical current when exposed to an oscillating magnetic field tuned at the same frequency. (Stray magnetic field interference is mitigated with this design.) The power supply may also have an AC/DC converter to exclusively direct current to pass through the positive and negative leads.