CN113797444A

CN113797444A - Application method of rhinitis therapeutic apparatus

Info

Publication number: CN113797444A
Application number: CN202110961521.3A
Authority: CN
Inventors: 李得霞
Original assignee: Individual
Current assignee: Individual
Priority date: 2021-08-20
Filing date: 2021-08-20
Publication date: 2021-12-17

Abstract

The invention discloses a use method of a rhinitis therapeutic apparatus, which comprises the following steps: step one, subcutaneously implanting a therapeutic assembly in a patient such that at least one therapeutic assembly is positioned in the autonomic nervous system adjacent a target location, the therapeutic assembly comprising at least one electrode configured to deliver an electrical current to the target location, the therapeutic assembly may comprise at least one electrode configured to deliver a therapeutic signal, such as an electrical current, to the target location; step two, delivering current to the at least one electrode to effect changes in the autonomic nervous system; and step three, sensing at least one physiological parameter related to the rhinitis through the treatment assembly. The method of use of the rhinitis treatment apparatus provides immediate relief from symptoms after the treatment is administered without systemic side effects, while delivering the treatment as needed to improve the quality of life of the patient.

Description

Application method of rhinitis therapeutic apparatus

The technical field is as follows:

the invention relates to the field of medical treatment, in particular to a use method of a rhinitis therapeutic apparatus.

Background art:

rhinitis is an inflammatory condition of the nasal passages and is often characterized by symptoms such as nasal drainage, nasal itching, sneezing, and/or nasal congestion. Acute rhinitis, such as that associated with viral upper respiratory tract infections, usually resolves after immune clearance of the infectious organism. In contrast, patients with chronic rhinitis tend to have a clinical course characterized by long-lasting or recurring symptoms. Rhinitis has affected nearly one-eighth of the chinese population, and has had a significant impact on overall health and productivity. Rhinitis has been shown to be a possible predictor of future asthma in children. Rhinitis also leads to poor learning and performance. Chronic rhinitis is broadly divided into allergic and non-allergic forms. Traditionally, allergic rhinitis has been classified as seasonal or perennial. However, this classification is challenging because many patients are sensitive to both seasonal and perennial allergens. Newer classifications based on the time axis (intermittent or persistent) and severity (mild or moderate/severe) of symptoms are increasingly used. Treatment of allergic rhinitis depends on the severity and persistence of the symptoms. The main content of the drug therapy includes one or more of the following, and is tailored to the patient's response and tolerability; a steroid leukotriene receptor antagonist; a leukotriene synthesis inhibitor; mast cell stabilizers; anticholinergic agents; and monoclonal antibody therapy.

Avoiding offending pollen or food is also a major means of treatment. For those patients who cannot tolerate failure of medication, allergy immunotherapy may be used as a treatment option. Although immunotherapy can be very effective, it is often necessary to perform weekly treatments (subcutaneous injections) for several years weekly in the office of the attending physician to achieve long-term efficacy. In addition, many patients with overt symptoms remain symptomatic despite ongoing immunotherapy.

Non-allergic rhinitis (NAR) is similar to allergic rhinitis, although ocular symptoms such as redness, itching or tearing are less pronounced in NAR. The classification of NAR is simple, as NAR has many subtypes, including inflammatory and non-inflammatory. Inflammatory non-allergic rhinitis may be associated with NAR in occupational exposure, medications (including prescription and over-the-counter), infections, and hypereosinophilic syndrome. Non-inflammatory NAR may be one of the following forms, emotional agitation; idiopathic atrophy; gustatory vasomotor; hormones or drugs associated with drugs (e.g. rhinitis medicamentosa). The purpose of treatment is to address the offending etiology (e.g., discontinuing the use of topical congestion agents for patients with drug-induced rhinitis). In some cases, steroids, antibiotics, anticholinergics or other drugs described for allergic rhinitis may be helpful. However, for many patients with NAR, there is no optimal or effective treatment method, and based on the characteristic treatment methods of traditional Chinese medicine, a series of rhinitis treatment apparatuses have appeared in the prior art, which have substantially the same structure and comprise a control unit and electrodes, and the electrodes usually have a drug guiding function, such as an automatic drug guiding electrode for rhinitis disclosed in chinese patent publication No. CN2162256, and an on-off rhinitis treatment apparatus disclosed in CN206660325U, but such rhinitis treatment apparatuses usually only have the effect of relieving rhinitis symptoms, and are difficult to achieve the purpose of effective treatment.

The invention content is as follows:

the invention aims to solve the technical problem of providing a using method of a rhinitis therapeutic apparatus capable of improving the treatment effect on rhinitis.

The technical scheme of the invention is to provide a using method of a rhinitis therapeutic apparatus, which comprises the following steps:

step one, subcutaneously implanting a therapeutic assembly in a patient such that at least one therapeutic assembly is positioned in the autonomic nervous system adjacent a target location, the therapeutic assembly comprising at least one electrode configured to deliver an electrical current to the target location, the therapeutic assembly may comprise at least one electrode configured to deliver a therapeutic signal, such as an electrical current, to the target location;

step two, delivering current to the at least one electrode to effect changes in the autonomic nervous system;

sensing at least one physiological parameter related to rhinitis through the treatment assembly;

step four, then, in response to the sensed at least one physiological parameter, adjusting the treatment assembly to adjust the application of the electrical current to the target site to treat the rhinitis. The electrodes may include at least one electrode in electrical communication with a power source (not shown), which may include a battery or generator, such as a pulse generator operatively connected to the electrode, which may be placed at any suitable location, such as integrated as part of a therapeutic assembly, adjacent the electrode, at a remote location within or on the subject's body. Based on the implantation requirements, one type of power source may include an implantable generator, which may be similar to a cardiac pacemaker.

It should be noted that the rhinitis treatment apparatus with which the present disclosure is engaged may include any rhinitis treatment device, apparatus, or combination thereof configured to deliver therapeutic signals to the neural structures or neural tissue of the present invention.

Preferably, the target site is a neural structure associated with the alar fossa.

Preferably, the neural structure includes at least one of a retinal nerve or a sphenopalatine nerve. The terms "neural tissue" and "neural structure" may refer to any tissue of the autonomic nervous system, including, but not limited to, neurons, axons, fibers, bundles, nerves, plexuses, afferent plexus fibers, efferent plexus fibers, ganglia, preganglionic fibers, postganglionic fibers, cervical sympathetic ganglia/ganglia, thoracic sympathetic ganglia/ganglia, afferents, efferents, and combinations thereof.

Preferably, the autonomic nervous system is modulated to alter at least one of mucosal blood flow, mucosal thickness and mucosal secretion.

As a preferred aspect, the step of implanting a therapeutic assembly includes positioning the therapeutic assembly near a target location, wherein the sensing step further includes: generating a sensor signal based on the sensed at least one physiological parameter; and adjusting the therapy assembly in response to the sensor signal to adjust the application of the electrical current to the target site to treat rhinitis. Where the physiological parameter is a change in inflammatory cells (e.g., eosinophils, neutrophils, macrophages or lymphocytes), proteins, cytokines, chemokines, intraluminal gas, histamine, leukotrienes, nitric oxide (and its synthetases and metabolites) or other innate or acquired markers/compositions, adaptive mucosal or systemic immunity can be monitored/detected and the system can be adjusted to account for these changes. In addition, changes in temperature, pH, mucosal edema, changes associated with mucosal remodeling (e.g., basement membrane thickness, epithelial damage), venous congestion, blood flow, mucosal hydration, and rhinorrhea can be monitored or detected. Also, the physiological parameter may include local or systemic conditions or changes, such as other general or molecular changes in chronic or refractory rhinitis. Examples of such molecular changes may include up-regulation or down-regulation of various proteins (or their receptors). In addition, the inflammatory cell distribution of the nasal mucosa can be monitored. For example, relative or absolute eosinophil, neutrophil, macrophage or lymphocyte counts can be determined. Changes in dendritic cells or related proteins may also be used. Other markers may include nitric oxide or its synthetases or metabolites, oxygen tension and markers of ciliary dysfunction or mucociliary insufficiency. Microorganisms or their by-products may also be used as markers. For example, bacteria, staphylococcus aureus, fungi or viruses, and by-products of these or other organisms.

As a preferred technical solution, the therapeutic assembly further includes an implantable neurostimulator, and the implantable neurostimulator is electrically connected to at least one electrode of the therapeutic assembly.

As a preferred solution, the electrodes of the therapeutic assembly are any one of unipolar, multi-polar or bipolar, and the electrodes may function as cathodes or anodes. The electrodes may be composed of one or more conductive materials, for example, activated iridium, rhodium, titanium, platinum, or combinations thereof. All or only a portion of the electrodes may be coated with a thin surface layer of iridium oxide, titanium nitride or other surface modification to enhance electrical sensitivity.

As a preferred technical solution, the electrode device further comprises a controller, and the controller is used for wirelessly operating the electrode and/or supplying power to the electrode. The controller may include a fixation plate (e.g., made of titanium) that uses standard anterior craniofacial screws to allow the implantable neurostimulator to attach to the bone structure surrounding the PPF. The controller may be powered by the rhinitis treatment apparatus or by an independent power source. The controller may vary the power output to the electrodes by polarity, pulse width, amplitude, frequency, voltage, current and/or waveform.

In a further aspect, where the rhinitis treatment apparatus includes a drug port, the controller can vary its output to cause the pump, pressure source or proportionally controlled orifice to increase or decrease the rate at which the pharmacological or biological agent is delivered to the target site. That is, where the rhinitis treatment apparatus includes a drug port or other fluid delivery mechanism for delivering at least one pharmacological or biological agent to a target site. A drug port or other fluid delivery mechanism may be fluidly connected to a reservoir, which may be implanted within the subject or remote from the subject, by needle insertion. Any one or combination of pharmacological or biological agents may be delivered to the target site. The pharmacological or biological agent may include, among others, agents, molecules, cells, compounds, etc. capable of modulating autonomic nervous system activity. Agents, molecules, cells, compounds, etc. (e.g., anti-inflammatory agents) that can prevent or treat microbial infections may also be included. Moreover, the pharmacological or biological agent may be attached to a surface of the therapeutic component (e.g., one or more surfaces of the electrode), surrounded by and released through the carrier. In addition, the controller may operate any number or combination of electrodes and/or fluid delivery mechanisms. For example, the controller may be connected to a pump for delivering the electrical current and the pharmacological or biological agent to the target site. The controller may be implanted entirely within the subject, or alternatively, be positioned around the subject or be integrally provided on the rhinitis treatment apparatus.

Also, where the controller allows the delivery of current to the target location, the current may be periodic, continuous, phased, intermittent, on demand by the subject or medical personnel, or pre-programmed to respond to the sensor. The electrical signal and constant pulse width can be operated at a constant voltage (e.g., at about 0.2v to about 20v), at a constant current (e.g., at about 0.1 microampere to about 6 milliamps), at a constant frequency (e.g., at about 1 v). The application of current may be unipolar, bipolar or multipolar, depending on the polarity of the electrodes. The waveform may be biphasic, square wave, sinusoidal or other electrically safe and feasible combination.

In addition, where the controller is capable of delivering the pharmacological or biological agent to the target location, the pharmacological or biological agent may be delivered to the target location prior to, simultaneously with, subsequent to, or in lieu of the electrical current. The pharmacological or biological agent may be a neurotransmitter mimetic, neuropeptide, hormone, prohormone, antagonist, agonist, reuptake inhibitor or its degrading enzyme, peptide, protein, chemical agent, amino acid, nucleic acid, stem cell, or any combination thereof, and may be delivered by a sustained release matrix or drug pump. The delivery of the pharmacological or biological agent may be continuous, intermittent.

Compared with the prior art, the invention has the following advantages after adopting the scheme: while not being able to eradicate chronic or refractory rhinitis, the present invention is effective in alleviating the symptoms of rhinitis in patients with rhinitis, advantageously, the present invention provides a method for aiding in or replacing current standard therapies for those standard therapies that are refractory to these standard therapies in patients with chronic or refractory rhinitis, and unlike conventional therapies that typically take months or years to achieve efficacy, the disclosed methods of treatment can provide symptom relief immediately after administration, and the present invention allows on-demand or continuous monitoring and treatment of symptoms associated with chronic or refractory rhinitis without systemic side effects, while also delivering therapy as needed to improve the quality of life of the patient.

The specific implementation mode is as follows:

the invention is further illustrated with respect to specific embodiments below:

a method for using a rhinitis therapeutic apparatus comprises the following steps:

delivering an electrical current to the at least one electrode to effect a change in the autonomic nervous system, in this embodiment, a modulation of the autonomic nervous system to alter at least one of mucosal blood flow, mucosal thickness, and mucosal secretion;

sensing at least one physiological parameter related to rhinitis through the treatment assembly; the physiological parameter is, among others, inflammatory cells (e.g., eosinophils, neutrophils, macrophages or lymphocytes), and the system can be modulated to account for these changes. In addition, changes in temperature, pH, mucosal edema, changes associated with mucosal remodeling (e.g., basement membrane thickness, epithelial damage), venous congestion, blood flow, mucosal hydration, and rhinorrhea can be monitored or detected. Also, the physiological parameter may include local or systemic conditions or changes, such as other general or molecular changes in chronic or refractory rhinitis. Examples of such molecular changes may include up-regulation or down-regulation of various proteins (or their receptors). In addition, the inflammatory cell distribution of the nasal mucosa can be monitored. For example, relative or absolute eosinophil, neutrophil, macrophage or lymphocyte counts can be determined. Changes in dendritic cells or related proteins may also be used.

As a preferred aspect, the step of implanting a therapeutic assembly includes positioning the therapeutic assembly near a target location, wherein the sensing step further includes: generating a sensor signal based on the sensed at least one physiological parameter; and adjusting the therapy assembly in response to the sensor signal to adjust the application of the electrical current to the target site to treat rhinitis.

In addition, as a preferred technical solution, the therapeutic assembly further includes an implantable neurostimulator, and the implantable neurostimulator is electrically connected with at least one electrode of the therapeutic assembly. The electrodes of the therapeutic assembly are any of unipolar, multi-polar, or bipolar, and the electrodes may function as cathodes or anodes. The electrodes may be comprised of one or more conductive materials, such as a combination of activated iridium, titanium. All or only a portion of the electrodes may be coated with a thin surface layer of iridium oxide, titanium nitride or other surface modification to enhance electrical sensitivity.

In this embodiment, a controller is also included for wirelessly operating and/or powering the electrode. The controller may include a titanium fixation plate that uses standard anterior craniofacial screws to allow the implantable neurostimulator to attach to the bone structure surrounding the PPF. The controller may be powered by the rhinitis treatment apparatus or by an independent power source. The controller may vary the power output to the electrodes by polarity, pulse width, amplitude, frequency, voltage, current and/or waveform. The controller, in the case of a rhinitis treatment apparatus including a drug port, may vary its output to cause a pump, pressure source or proportionally controlled orifice to increase or decrease the rate at which a pharmacological or biological agent is delivered to a target site.

By cooperating with the rhinitis treatment apparatus, in one aspect, a therapeutic signal (e.g., an electrical current) can be delivered, such as to a target site, effectively blocking or reducing parasympathetic activity. Blocking or reducing parasympathetic activity can reduce or alleviate at least one symptom associated with chronic or refractory rhinitis, such as swelling of the nasal mucosa and mucosal secretion. For example, a retardation or reduction in parasympathetic activity may cause a reduction in swelling of the nasal mucosa, resulting in a reduction in nasal congestion. In another aspect, a therapeutic signal (e.g., an electrical current) can be delivered (e.g., selectively delivered) to a target location, such as a sympathetic fiber including an SPG. Substantially activates or increases sympathetic nerve activity. Activating or increasing sympathetic nerve activity can reduce or alleviate at least one symptom associated with chronic or refractory rhinitis, such as mucosal blood flow and mucosal thickness. For example, activation or increase of sympathetic nerve activity may promote arterial vasoconstriction, thereby reducing mucosal blood flow and mucosal thickness in addition to restoring nasal patency.

The present invention has the advantage that although chronic or refractory rhinitis cannot be eradicated, it is effective in alleviating the symptoms of rhinitis in patients with rhinitis, and advantageously provides an adjunct or alternative to current standard treatments for those standard treatments which are refractory to these standard treatments in patients with chronic or refractory rhinitis, unlike conventional treatments which typically take months or years to reach efficacy, the treatment methods of the present disclosure can provide symptom relief immediately after implementation, and it allows on-demand or continuous monitoring and treatment of symptoms associated with chronic or refractory rhinitis without systemic side effects, while also delivering treatment as needed to improve the quality of life of the patient.

The foregoing is illustrative of the preferred embodiments of the present invention only and is not to be construed as limiting the claims. All the equivalent structures or equivalent process changes made by the description of the invention are included in the scope of the patent protection of the invention.

Claims

1. The application method of the rhinitis therapeutic apparatus is characterized in that: the method comprises the following steps:

step one, subcutaneously implanting a therapeutic assembly in a patient such that at least one therapeutic assembly is positioned in an autonomic nervous system adjacent a target location, the therapeutic assembly comprising at least one electrode configured to deliver an electrical current to the target location;

step four, then, in response to the sensed at least one physiological parameter, adjusting the treatment assembly to adjust the application of the electrical current to the target site to treat the rhinitis.

2. The method of using the rhinitis treatment apparatus of claim 1, wherein: the target location is a neural structure associated with the alar fossa.

3. The method of using the rhinitis treatment apparatus of claim 1, wherein: the neural structure includes at least one of a retinal nerve or a sphenopalatine nerve.

4. The method of using the rhinitis treatment apparatus of claim 1, wherein: the autonomic nervous system is modulated to alter at least one of mucosal blood flow, mucosal thickness, and mucosal secretion.

5. The method of using the rhinitis treatment apparatus of claim 1, wherein: the step of implanting a therapeutic assembly includes positioning the therapeutic assembly near a target location, wherein the sensing step further includes: generating a sensor signal based on the sensed at least one physiological parameter; and adjusting the therapy assembly in response to the sensor signal to adjust the application of the electrical current to the target site to treat rhinitis.

6. The method of using the rhinitis treatment apparatus of claim 1, wherein: the therapeutic assembly further includes an implantable neurostimulator electrically connected to at least one electrode of the therapeutic assembly.

7. The method of using the rhinitis treatment apparatus of claim 1, wherein: the electrodes of the therapeutic assembly are any of unipolar, multi-polar, or bipolar, and the electrodes may function as cathodes or anodes.

8. The method of using the rhinitis treatment apparatus of claim 1, wherein: a controller is also included for wirelessly operating and/or powering the electrodes.

9. The method of using a rhinitis treatment apparatus in accordance with claim 8, wherein: the controller, in the case of a rhinitis treatment apparatus including a drug port, may vary its output to cause a pump, pressure source or proportionally controlled orifice to increase or decrease the rate at which a pharmacological or biological agent is delivered to a target site.