CN101500643A - Treatment of eating disorders using electrical impulse intervention - Google Patents

Abstract

Devices and methods for treating patients suffering from an eating disorder, such as obesity and/or pathologies resulting in obesity, by regulating sensations affecting food consumption. The devices and methods may facilitate appropriate caloric intake, thereby inducing weight loss, by simulating, stimulating, amplifying, blocking and/or modulating signals in the gastrointestinal (GI) tract and/or nerves innervating the GI tract, to manage sensations of hunger and satiety, such as controlling hunger by signaling the gastrointestinal tract and/or gastrointestinal nerves when different hunger sensations are detected.

Description

Utilize electric pulse to get involved and treat eating disorder

Technical field

The present invention relates to the field that be used for the treatment of purpose of electric pulse, relate more specifically to be used for the treatment of and suffer from one or more eating disorder, for example the patient's of the obesity that causes of obesity and/or pathological changes apparatus and method to bodily tissue output.

Background technology

Over nearly 2000, electricity irritation is used for the purposes of medical science health status treatment by known in the art.Roman physicians is in the news and uses electric eel to treat headache and the pain relevant with gout.1760, John Wesley applied for the original rudimentary electric device that is used for the treatment of purpose, Leyden jar (the Leyden Jar), and wishing is used to shock by electricity suffers from the patient of paralysis, convulsions, epilepsy, headache, angor and sciatica.

Up to 1791, Luigi Galvani has just done subject research at muscle and neural live action in the mode of the strictness that conforms with science.1793, Alessandro Volta further did this work, when he reports near the energising metal is placed in nervus motorius, forced the generation muscle contraction, and described muscle is subjected to described innervation.

Modern Application the most successful of this basic comprehension that concerns between muscle and the nerve is a cardiac pacemaker.Though its origin extended to for 19th century, just implement for the first time up to nineteen fifty, and exploitation is the pacemaker of external heaviness.Dr.Rune Elqvist has developed first that work really, wearable pacemaker in nineteen fifty-seven.Shortly after that, in nineteen sixty, the pacemaker of first totally implantable is developed.

Near this time, find also and can electric lead be connected to heart that it has been cancelled and opens the thoracic cavity and be connected the needs of lead to heart wall by vein.Introducing at lithium-iodine battery in 1975 has extended to the battery life of pacemaker above 10 years from some months.Modern pacemaker can be treated the pathological changes of various unlike signals in the cardiac muscle, also can be used as cardiac defibrillator (see to license to Deno, the United States Patent (USP) 6,738,667 of et al., it openly is hereby incorporated by).

The Another application of nerve electric stimulation is to treat radiating pain in the extremity bottom (see the United States Patent (USP) 6,871,099 that licenses to Whitehurst etc., its disclosure is hereby incorporated by) by stimulating at the sacral nerve roots of spinal cord bottom.

Further use and be disclosed the United States Patent (USP) 6 that the name that licenses to Schuler etc. is called " Implantablemethod to regulate blood pressure by means of coded nervesignals ", 957, in 106 (" ' 106 "), it is incorporated herein by reference in full at this." electricity that emits via the vagus nerve bundle from the medulla oblongata pons zone is to regulating the effect of cardiovascular blood pressure " stated in patent ' 106.Therefore, the electro ultrafiltration that influences the vagus nerve bundle can influence the adjusting of blood pressure, makes vagus nerve become the further object of study of electricity irritation research.

It is that it is to send from oblongata via vagal (or cranial nerve,tenth) that most of life of human or animal body is kept control.Oblongata or neck level paralysis or cut off two vagus nerves can be fatal rapidly.This nerve is actually the long nerve tract that imports into efferent neuron, and it comprises stomach by the inner most organs that arrives of body.Vagus nerve emits from all directions of oblongata, and arrives identical target organ by different paths.For example, left vagus nerve is being arranged the preceding upper surface of stomach.

The nerve of domination stomach is the end branch of right and left vagus nerve, and the former is assigned to the back side, and the latter is assigned on the previous section of organ.A large amount of branches from orthosympathetic solar plexus also are assigned to above it.Plexus nervorum is found in the tela submucosa and is between the flesh layer in intestinal the time.From these clumps, fubril is assigned to muscular tissue and mucosa.

Stomach is the most expansible part of digestive tract, between the starting point of the end of esophagus and small intestinal.Stomach exists two openings, two edges or crooked and two surfaces.When stomach was in the contraction situation, its surface was respectively up and down, but when internal organs are expanded, and they are forward and backward.Therefore, they can be called as before on the back under.

About preceding upper surface, left-half contacts with barrier film, and barrier film is separated the intercostal space in the bottom of left-half and left pulmonary, pericardium and the 7th, the 8th and the 9th rib and left side.Lobus sinister of right half part and liver and quadrate lope and interrelate with preceding stomach wall.When stomach was sky, transverse colon can be positioned on these surperficial forward part.Whole surface is covered by peritoneum.

The last contacting phase layer of the top of the front of back lower surface and diaphragm, spleen, left side adrenal gland, left side kidney, the front surface of pancreas, left side colic flexure and transverse mesocolon.These structures have formed surface bed, the stomach bed, and internal organs are had a rest thereon.Transverse mesocolon is separated stomach and duodenojejunal flexure and small intestinal.Back lower surface is covered by peritoneum, except approaching a zonule of cardia; This zone is limited by the attached wire of gastrophrenic ligament, is positioned at diaphragm side by side, and usually is arranged side by side with adrenal top, left side.

For the component part of stomach, it is by being illustrated in Fig. 3 A, and the bundle of planes gastric stapling that passes expansible limit on the left relative on angular incisure and the greater gastric curvature on the lesser gastric curvature is left half or body portion and the right side or pylorus part.The left half of body is called as substrate, is demarcated by the remainder of the plane of level by cardia from body.The pylorus part is separated by intermediate sulcus and this vertical plane of part major axis, and this planar right half is a pyloric antrum.

On the physiology, stomach is the door as food consumption, so the increase of weight, causes overweight symptom and obesity.Many people have ungratified diet desire, so overfeeding, cause overweight conditions and fat sometimes.If the people has 25 or the score of bigger Body Mass Index (BMI), it is overweight that individuality is considered to, and described Body Mass Index is the survey tool that is used to determine excessive body weight.People's BMI score be him with kilogram body weight of representing and the height of representing with rice square ratio (that is kg/m, ²).Have 30 or the people of higher BMI score be considered to fat, yet have 40 or those of higher BMI score be considered to serious obesity.

Ended by 2002 o'clock, only estimate that in U.S.'s overweight conditions and fat quilt influence surpasses 127000000 adults and above 9000000 children, several hundred million people arranged in the whole world.About about 127000000 overweight adults in the U.S., about 60000000 are considered to fat, and these 9000000 in 60000000 are considered to serious obesity.Press percentage rate, this means U.S. of 64.5% adult is overweight, the 30.5%th, fat with 4.7% be serious fat.

It is chronic disease that Center for Disease Control (CDC) (CDC) calls fat and overweight conditions, and it has changed epidemic diseases into.Overweight, and spreading range is to fat, increase the risk of many health status and disease, comprise hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, apoplexy, gallbladder disease, osteoarthritis, sleep apnea, breathing problem and even some cancer (endometrial, chest and colon).Though carried out many minimizing overweight conditions and fat popular effort, adult that data show is overweight and fat and child's number are increasing.

Overweight conditions and obesity are also increasing government and medical expenditures.In 2003, CDC infer the taxpayer paid 39,000,000,000 dollars with fat relevant medical fees, relate to more than half part of 75,000,000,000 dollars of that years and the relevant medical fee of obesity.This number is the numeral for the treatment of fat relevant medical problem by medical care insurance (Medicare) and Medicaid (Medicaid).In the U.S., fat relevant account to give accounts for about 10% of approximately total medical science expenditure.Every year, only the California just spend about 7,700,000,000 dollars on the relevant therapeutic treatment of obesity.

When mentioning obesity, speech remains on that it is relevant with our diet.Food consumption provides energy to health, and be calculated as, and be considered to, calorie, it is that health performance function is needed.The metabolic conversion calorie of health is a fuel, is used for physical activity.Depend on the physical activity level with respect to heat loss, calorie will be acted as a fuel by metabolism and directly use, and perhaps be stored as and use after fat is used for.When the fuel that is used for directly using of health became deficiency, the release of appetite hormone can cause that individuality feels hungry, and therefore ate.Eat and discharge the hormone of triggering satiety, it will cause individuality to stop to eat.

The disappearance of satiety or the sensation of swelling and the back appetite of having meal is the process of regulating by ventromedial nucleus in the hypothalamus, is called as " satiety center ".Various hormones at first are cholecystokinins, have related to the transmission of satiety to brain.Leptin increases satiety, and ghrelin increases when stomach is sky.Therefore, satiety is meant psychological gratification after diet, rather than the physical sensation after referring to be filled, and, is eating the very big full sensation of physics after the meal that is.Satiety directly influences the appetite sense that forms in limbic system, by hunger sensation, the especially serotonin in lateral hypothalamus of neuro hormone control.Preferably, satiety causes individuality to stop diet.

Leptin with other hormones, is used with control appetite and metabolism by health.More particularly, Leptin is the proteohormone of 16kDa, and it has played the part of pivotal player in regulating caloric intake and energy expenditure.Leptin produces by being positioned at people's the 7th chromosomal 0b (Lep) expression of gene, by fatty tissue (that is, it discharges from adipose cell).The loose connective tissue that fatty tissue is made up of adipose cell, it mainly acts on is form storage power with fat, though it also cushions and be incubated health, and for example carries out important endocrine function among Leptin, phylaxin and the TNF α producing hormone.

The acceptor interaction (LepRa-LepRf) of Leptin and six types.LepRb is unique receptor subtype that comprises movable intracellular signal territory, is present in many nucleus hypothalamicuses, and here it brings into play its effect.Importantly, Leptin is attached to hypothalamic ventromedial nucleus, perhaps aforesaid " satiety center ".Leptin to the combination of these nuclears has provided signal to brain: it is abundant that health has been eaten--satiety.Human very little colony mainly is from the inbreeding crowd, is the variant of Leptin gene.The diet that these people pause hardly and possible overweight before 7 years old greater than 100 pounds (45 kilograms).

Leptin play a role be by suppressing to comprise neuropeptide tyrosine (NPY) and agouti-related peptide (AgRP) neuronic activity and by the increase neuron expression alpha-Melanocyte stimulating hormone (activity of α-MSH).The NPY neuron is the key element in the appetite stimulator; Low dose of NPY is injected into laboratory animal and has excited and ingest, and the neuronic selective destruction of NPY causes their anorexia that becomes in the mice.On the contrary, α-MSH is that the difference in the important medium of satiety and the brain of the acceptor gene act in to(for) α-MSH is that obesity with the people interrelates.At night, Leptin is also regulated (downwards) by melatonin.

In case Leptin is attached to the Ob-Rb receptor, its activating molecules stat3, its be phosphorylation and move to ventromedial nucleus, described ventromedial nucleus is supposed, to influence the variation of gene expression.In their many other functions, a main effect in gene expression is the downward modulation that interior Cannabinoids is expressed, and it causes appetite to increase.Having other born of the same parents' internal channels to be activated by Leptin, seldom is known but how to play a role in this system about them.Response Leptin, receptor neuron have shown the configuration that changes oneself, change the number and the type that are applied to the synapse on them.

Leptin discharges by adipose cell, has quantitatively reflected whole body fat reserves.Therefore, the Leptin level in the circulation has given the reading of energy storage to brain, is used for modulation of appetite and metabolic purpose.Though Leptin is the cycle signal that reduces appetite, usually, the quantity of the Leptin of generation increases along with the increase of body weight, and therefore fat people has significantly high Leptin circulation composition.The increase of Leptin level will produce the signal that increases, and be used for health and take in less food.Yet overweight and fat people it seems has resistance to the signal of carrying by Leptin, has promoted their over-drastic food intakes.

Some fat people it is said that coming has resistance to the effect of Leptin to resist the roughly the same mode of insulin action with the people that type 2 diabetes mellitus is arranged.Usually, when people continue for some time produce when take in surpassing the energy that they use fat.In the Leptin resistant obese people, this excessive dietary intake is not driven by the hunger sensation signal, and the anti-appetite signals of Leptin also takes place in the self-loopa although have.Continuing concentration from the high Leptin of the fat stores that enlarges causes the cell that Leptin the reacts desensitization that becomes.

Undue heat is taken in and has been caused the excess energy imbalance, and wherein caloric consumption and caloric use are disproportionate, for example pass through physical activity.Continue for some time the final cause that the excess energy imbalance is overweight conditions and obesity takes place repeatedly.For given individuality, the uneven dynamic factor of this energy of many influences is arranged, comprise the use of selectivity, disease and medicine of selectivity, the physical activity of individual heredity, environment, diet.Tragic ground, many overweight and fat people though know their problem, think that it has exceeded their control.

There are many control appetite and increase physical activity, to make great efforts the controlling body weight increase and to excite the trial that loses weight.These trials comprise the medicine that is used for appetite-suppressing, dietary program, dangerous operation and psycheism.Although many in these body weight control methods have shown initial result, in case the arrival plateau of losing weight individually often return to the previous behavior that causes weight increase.

Instructed many electric devices and method in this area, be used to attempt controlling the individual food intake and/or the various aspects of digestion process, to make great efforts treatment diet or digestive disorders.Some formerly technical literature concentrate on the motion of food.Chen, et al., U.S. Patent number 5,690,691, the stomach pacemaker that is implanted in the gastrointestinal tract is disclosed, coordinate wriggling with the electricity irritation of transmitting stage by stage, strengthen or promote the wriggling by the stomach tube road or slow down wriggling, treat this eating disorder or symptom of diarrhea.Similarly, Terry, Jr., et al., U.S. Patent number 5,540,730 discloses the apparatus and method for the treatment of the power disorder, by optionally exciting patient's vagus nerve, regulate the electroactive of nerve, cause that therefore the selectivity of irritability or inhibitory transmitter discharges or inhibition.Concrete scheme has adopted the craft of implanting device or has excited automatically, is used for optionally regulating.Similarly, Cigaina, U.S. Patent number 5,423,872, disclose be used for the treatment of obesity with the method and apparatus of the disorderly relevant syndrome of gastric motility, prevent emptying or slow down the intrinsic gastric motility that changes the patient through coming of food by electricity irritation.

U.S. Patent application 20050222637 to Chen, title TachygastrialElectrical Stimulation, it is introduced by reference at this, disclosing the treatment obesity is " to come the intrinsic gastric motility of manual change patient by means of the electric pulse that presets the period, to stop gastric emptying or to slow down stomach by increasing satiety and/or promoting intestinal by reducing the soak time in intestinal.More particularly, tachygastria is induced in electricity irritation, and it suppresses gastric motility, produces gastric distension and postpones gastric emptying.The tachygastria electricity irritation of stomach or other parts of gastrointestinal comprises long relatively pulse width, and the highest 500 milliseconds length is arranged ".

Other formerly technical literature concentrate on the sensation aspect of food ration.Zikria, U.S. Patent number 6,564,101, the system that utilizes electrical signal control to be used to control patient's appetite is disclosed, described electrical signal control transmits the electrical signal to the bottom of patient's stomach, and its middle controller produces successive basically low pressure to stimulate, and the cycle of the variation of measuring by the specific physiology of individuality, dissection and/or psychology is arranged.

Wernicke, et al., United States Patent (USP) 5,188,104 (" ' 104 "), it, discloses and has utilized the vagus nerve electricity irritation to treat the method and apparatus that forces diet disease patient by with reference to introducing at this.' 104 patent proposes " detect the preselected event indication that presses for treatment of target special diet disorder, the generation of the preselected event that response detects is used the predetermined suitable effect that alleviates target eating disorder of stimulus signal to patient's vagus nerve ".

' 104 indicate, and are forcing under the situation of excessive diet " stimulus signal is scheduled to produce satiety in the patient ".Yet, if " disorder is to force refusal diet (anorexia nervosa), and stimulus signal is scheduled to produce the satiety among hunger sensation or the inhibition patient ".

In ' 104 patents, preselected event can be, for example, " setting-up time at interval in patient's specific food ration level; or according to the circulate beginning of conventional meal time of patient's physiological rhythm; or stage of at interval each of preset time, or by beginning the application of stimulus signal voluntarily to vagus nerve, patient oneself recognizes to be needed to treat ".' 104 patents suggestion ＂ swallows the generation of the number ＂ detection preselected event of food by patient in the interval that is accumulated at setting.

Yet said apparatus does not have enough the effectively fat relevant eating disorder of treatment.Therefore, have in this area treatment is promoted the new product of fat medium of excessive food consumption and the demand of method.

Brief summary of the invention

The present invention relates to be used to regulate the product and the method for the impression that influences food ration, as for suffering from one or more eating disorder, the patient's of for example fat and/or pathological changes that causes fat treatment, utilization can be applied to the signal of telecommunication of gastrointestinal tract and/or gastrointestinal tract nerve, with temporary stimulation, enhancing, blocking-up and/or the adjusting nerve signal relevant with satiety and/or hunger sensation.The present invention comprises causeing fat, and conventional and serious fat both treatment of pathological changes is for example the patient that the thyroid pathological changes is arranged with suffer from the Drug therapy side effect or Cushing's disease (among those patients of Cushing ' sdisease).The treatment of this obesity can be attended by the treatment to other health status, and for example melancholy, it also can take place under the weight increase situation.

In the first concrete scheme; the present invention focuses on to regulate influences food ration and/or treatment eating disorder; the method of the impression of the pathological changes that mainly is fat and/or causes fat; utilize electrical signal detection and transporter (ESDD); it detects the signal relevant with food ration that the patient produces; the signal that the modeling patient produces; and transmit the zone of one or more electric pulses at least one selection of gastrointestinal tract and/or domination gastrointestinal nerve, with stimulation, enhancing, blocking-up and/or the adjusting signal relevant with satiety and/or hunger sensation.Method can also comprise programming ESDD device, to carry out specific sensation and semiotic function.

In the second concrete scheme, the present invention focuses on electrical signal detection and transporter, is used to regulate the sensation that influences food ration, for example satiety and/or hunger sensation.Device comprises can detect the pick off that the patient relevant with food ration forms signal (PGS); Can simulate, stimulate, strengthen and/or block the control unit that the patient forms signal; Transmit the electric pulse generator of one or more electric pulses at least one selection zone of gastrointestinal tract and/or domination gastrointestinal nerve; Be used for perception PGS and/or transmit electrode and/or the lead of electric pulse with stimulation, enhancing, blocking-up and/or the adjusting PGS relevant with food ration; And power supply.The ESDD device also can comprise receptor or optional transceiver, is used for communication information, setting, data or the like between programming unit and control unit.

In different preferred embodiment, pulse is to use in the mode of the satiety signal of the hunger sensation signal of blocking-up patient formation and/or simulation or enhancing patient formation.In this respect, the simulation of the satiety signal of patient's formation comprises the signal relevant with specific sensation that duplicates patient oneself basically and give the patient with those signal feedback when suitable or expectation.This simulation can comprise the signal that strengthen to exist, or provides signal at needs or when expecting them to their non-existent positions.Obviously, the activation of this pulse depends on concrete scheme, can be by suffering from fat patient or patient's health care service personnel, for example control of doctor, nurse or nursing staff's automatic or manual.

Yet, major concern of the present invention be to induce to lose weight and treat obesity by reducing food ration, the present invention also is applied to serious anorexia case, wherein to come weight increase be desirable by increasing food ration.Under the situation that desired weight increases, pulse can be used with the hunger sensation signal of simulation or enhancing patient formation and/or the mode of the satiety signal that the blocking-up patient forms.

By settling lead on gastrointestinal tract and/or domination gastrointestinal nerve, the bottom section of stomach for example, hunger sensation and satiety are transmitted in described zone, for example a left side and right vagal end branch, with branch from the sympathetic nerve solar plexus, can detect the signal that the patient forms, and can apply pulse.Lead can be positioned in near-end or far-end, to comprise many or few tissue that is subjected to effect of signals respectively.It is also understood that and also can use no lead pulse known in the art to be used for using pulse to the target area.

Near the mechanism that the neural selection area of gastrointestinal tract and/or gastrointestinal tract is used suitable pulse can comprise the nervous tissue that the end of electric lead is fixed on control hunger sensation and satiety, electric pulse generator wherein lead and implantation or the outside linked together.Created the applied field that penetrates the target nerve fiber at the electric field that the end of lead produces, and caused stimulation, blocking-up and/or adjusting to the signal of destination organization.

Detailed Description Of The Invention part below, and with reference to the accompanying drawing of this paper and claims will be more complete the application of description electric pulse, described electric pulse be applied as or to gastrointestinal tract or to the gastrointestinal tract nerve with stimulate, blocking-up and/or regulate hunger sensation or satiety.

When associating accompanying drawing and the summary of the invention here, other purposes, feature, advantage or the like become apparent for a person skilled in the art.

Description of drawings

For various aspects of the present invention are described, have shown at present preferred scheme with the form of figure, yet be appreciated that the present invention is not limited to these accurate data, method, layout and the device of demonstration.

Fig. 1 is the sketch map of a sympathetic and parasympathetic nervous system.

Fig. 2 is the cross section internal anatomy of a neck, breast and abdominal part selection part.

Fig. 3 A illustrates the simple view of its part of harmonization of the stomach.

Fig. 3 B illustrates the simple view of the stomach with exemplary electrical signal detection and transporter, and described device is connected to the vagus nerve that shows among Fig. 1 and 2.

Fig. 4 is according to a concrete scheme of the present invention, illustrate one typically be used to stimulate, the electrical voltage/current profile figure of blocking-up and/or regulating impulse, described pulse is applied to one or more parts of gastrointestinal tract and/or domination gastrointestinal tract nerve.

Fig. 5 A and 5B illustrate exemplary complex copper micro-coil used according to the invention and its feature respectively.

Fig. 6 illustrates the flow chart of the typical implementation of the concrete scheme of the present invention.

Preferred forms

The purpose that is used for graphic extension has shown the preferred mode of the present invention in the accompanying drawings, and the present invention is not limited to the definite layout or the device of demonstration certainly.

With reference to figure 1, shown sympathetic and sketch map parasympathetic nervous system.Enjoyably, observed nervous system in the existing document and can keep balance by the signal of sympathetic nerve and parasympathetic nerves.From sympathetic nerve, stomach is by solar plexus innervation (showing from the left side).From parasympathetic nervous (be presented at here III, VII, VIII, IX, X and pelvis), remove the heart, larynx, trachea, bronchus, esophagus, abdominal part blood, Gan ﹠amp; Outside pipe, pancreas, small intestinal and the large intestine, vagus nerve (that is, X) is shown and extends to stomach downwards.

About Fig. 2, the cross section internal anatomy depicted in greater detail of neck, breast and abdominal part selection part vagus nerve.Vagus nerve is made up of motion and sensory fiber.Vagus nerve leaves head, and is contained in the identical dural sheath with accessory nerve.Vagus nerve passes to the neck root downwards along neck in carotid sheath.The parasympathetic nervous innervation of stomach is regulated by vagus nerve.The branch that vagus nerve distributes comprises, especially set one's heart, down the heart prop up, preceding bronchial branches and back bronchial branches.

On the right side, vagus nerve drops to the radix pulmonis rear portion along trachea, and here it spreads in rami cardiaci inferiores and the back plexus pulmonalis.The vagus nerve domination sinuatrial node on right side.Parasympathetic overstimulation brings out these affected positions and produces bradyarrhythmia.In the left side, vagus nerve enters chest, passes the left side of aortic arch, forms superior cardiac branches, and descends in the back of root of left lung, forms the back plexus pulmonalis.When excessive stimulating left vagus nerve, bring out heart and produce chamber (AV) retardance.

In mammal, two the vagus nerve parts of evolving out in brain stem are with parasympathetic function around the control.Back of the body vagus nerve complex (DVC), form by unlucky kinetonucleus (DMNX) and its junctional complex, control is lower than parasympathetic function of diaphragm level, and abdomen vagus nerve complex (VVC), form intraorganic function, for example heart, thymus and lung on the control diaphragm by nuclear behind ambigous nucleus and the nervus facialis, and other bodies of gland of neck and upper breast and tissue and specific muscle those of esophagus complex for example.

Vagal parasympathetic nervous division domination ganglion neuron, described ganglion neuron are positioned at or are adjacent to each target organ.Described abdomen vagus nerve complex be it seems and existed only in the mammal, and relates to the contraction of the forward relevant with excitatory state and negative regulation of heart rate, bronchoconstriction, sounding and facial muscle.Generally speaking, described vagus nerve is partly controlled parasympathetic state.Muscular tension (residue muscle tone) is that the successive and passive part of muscle is shunk.At vigilant state, the inhibition of described abdomen vagus nerve complex is disengaged (closing).

Parasympathetic nervous tension force partly by the sympathetic branch balancing, generally provides, and for example under the situation of heart and lung, is tending towards expanding the signal of cardiac muscle and lax muscularis of bronchus, and therefore excess shrinkage and excess oppress sensation does not take place respectively.Vagal excitement (tensile rise) for example takes place in shock, for example under the situation of heart and lung, causes heart rate to descend and airway constriction.

In this article, rise is the process that specific function is increased, and downward modulation comprises the reduction of effect.On cellular level, rise is that cell increases its number to given hormone or neurotransmitter receptor and improves its process to these molecule sensitivity.The minimizing of receptor is called as downward modulation.

According at least one aspect of the present invention, in suffering from fat or overweight patient, enough simulations, stimulation, enhancing, blocking-up and/or adjusting gastrointestinal tract and/or domination gastrointestinal tract nerve, for example the electric pulse of the transmission of the signal in the vagus nerve transmits, and will cause the adjusting relevant with satiety and/or hunger sensation.More particularly, this electric pulse is operationally to stimulate, strengthen, block and/or regulate the signal transmission of travelling to and fro between tissue and/or domination gastrointestinal tract nerve, with influence: hunger sensation, satiety, stomach satiety, the empty sense of stomach stomach function regulating pain.The simulation of the sensory signal that the patient forms comprises the signal relevant with the gastrointestinal tract specific sensation that duplicates patient oneself basically and give the patient with those signal feedback when suitable or expectation.This simulation can comprise the signal that strengthen to exist, or provides signal at needs or when expecting them to their non-existent positions.

The further refinement of method of the selection Zoned application electric pulse to gastrointestinal tract and/or domination gastrointestinal nerve described herein, be that at least one zone can comprise the nerve fiber that at least one comes from the tenth pair of cranial nerve of patient (vagus nerve), particularly, go up before at least one its and/or the back below.Similarly, at least one zone can comprise at least one rises from the orthosympathetic nerve fiber of patient, particularly, and solar plexus.

As required, pulse can directed gastrointestinal tract and/or gastrointestinal tract neurological region, and for example bottom section of stomach and/or vagus nerve are to simulate, to stimulate, to strengthen, to block and/or to be adjusted in the signal of gastrointestinal tract in propping up.As what those skilled in the art were familiar with, to carefully assess this concrete scheme before in known patient with electrophysiology problem, using.

About Fig. 3 A and 3B, Fig. 3 A illustrates the simple view of its part of harmonization of the stomach, yet Fig. 3 B illustrates the stomach with exemplary electrical signal detection and transporter 300, and described device is close to the vagus nerve 200 that is presented among Fig. 1 and 2.Electrical signal detection and transmission (ESDD) device 300 detects the signal (PGS) in stomach intestinal tissue and/or gastrointestinal tract nerve that the patient forms.The signal that these patients form and one or more relevant about the active sensation of patient's gastrointestinal tract by patient's identification, for example the satiety of hunger sensation, satiety, stomach, stomach are empty feels stomach function regulating and keenly feels.Detected signal model can be stored and with their physiological sensation interrelate (for example, hunger or satiety).PGS can be monitored and regulate periodically.In order to induce and to lose weight by reducing food ration, ESDD device 300 can be blocked for the PGS of hunger and simulation (for example, by stimulate and/or the strengthen) PGS for full abdomen.

ESDD device 300 can comprise electric pulse generator 310; The power supply 320 that links together with electric pulse generator 310; The control unit 330 that interrelates with electric pulse generator 310 and link together with power supply 320; With the electrode 350 that links together with electric pulse generator 310, power supply 320 and/or control unit 330, be used for being attached to the regional 200A of one or more selections, the 200B of gastrointestinal tract and/or gastrointestinal tract nerve, for example mammiferous vagus nerve 200 by lead 340.

Power supply 320 can connect 325 by power supply and link together with electric pulse generator 310 and control unit 330.Though ESDD300 needs power supply to play a role, power supply 320 can comprise detachable battery or other separable power supply 320S, and it can not accompany with ESDD300 when making or sell.Before using ESDD300, separable power supply 320S can be connected to power supply and connect 325.Therefore, the ESDD300 that has power supply connection 325 and do not have power supply 320 is also contained in the present invention.

Depend on configuration, each of electrode 350 and lead 340 can play signal, formation control impuls or both effects simultaneously that detects the patient and form.If use lead 340, preferred shield electrode 350 is so that electrode 350 plays the effect of the lead that lead 340 is connected with ESDD300.In context of detection, electrode 350 and lead 340 can be sensor electrode and inductive pickup coils.Combine with control unit 330, sensor electrode and/or inductive pickup coils can play the sensing element example.Aspect adjusting, electrode 350 and lead 340 can be pulsed electrode and inductive impulse coil.Combine with electric pulse generator 310 and control unit 330, pulsed electrode and/or inductive impulse coil can play the signal sending element example.If the bond area of expectation is too accurate for electrodes, preferably coil.

Be used to detection signal and produce the degree of pulse in order to reach single electrode 350 and/or lead 340, the function of control unit 330 transfer electrons 350 and/or lead 340 replaces between perception and transmission signal in case of necessity.Be transformed into perceptive function, control unit 330 receives the input of self-electrode 350 and/or lead 340.Be transformed into the transmission semiotic function, control unit 330 is regulated the signal output of electrode 350 and/or lead 340.

Device 300 can be self-contained, as shown, or is made up of various independent, interconnective units.Control unit 330 can be controlled electric pulse generator 310 and produce the signal that is fit to stimulate, strengthen, regulate and/or block PGS, and signal is applied to gastrointestinal tract and/or gastrointestinal tract nerve by electrode 350 and/or lead 340 when the time comes, and for example vagus nerve 200.By being connected to electrode 350 and lead 340, control unit 330 receives and pick-up transducers information.

Control unit 330 also can have receptor 360, can receive information from user's 380 exercisable programming units 370 by it.Receptor 360 can comprise extra power and drive (360e), or alternate, internal driver (360i), whereby control unit 330 can comprise complete, independently implant the unit.Receptor 360 can comprise transceiver, can transmission information get back to programming unit 370.Programming unit 370 can be external and be exercisablely to travel to and fro between control unit 330 with communication setting, information and data.

According to preferred concrete scheme, ESDD device 300 of the present invention is in the percutaneous mode or can be provided by the subcutaneous implantation mode that individuality reuses.

Use for percutaneous, ESDD device 300 can be by user 380 (for example, patient or healthcare attendant) as external appliance, and lead 340 and electrode 350 can be implanted to the patient whereby, traverse skin in order to be connected with ESDD device 300 but have link 340E.For subcutaneous application, ESDD device 300 can be that surgery is implanted, for example in the subcutaneous pocket of abdominal part.Depend on configuration, ESDD device 300 can be from health externally fed and/or charging or can have its own power source 320.For instance, ESDD device 300 can be by commercial purchase.Preferably, ESDD device 300 is programmed by the doctor programmer, for example can be from Medtronic, and the model 7432 that Inc. obtains.

In the obese patient, one or more ESDD devices 300 can be implanted to the regional 200A of one or more selections, the 200B of gastrointestinal region.U.S. Patent Application Publication 2005/0075701 and 2005/0075702, the both is Shafer, the both is hereby incorporated by, and relates to the neuron that stimulates sympathetic nervous system with the reduction immunoreation, has comprised the description that may be applicable to pulse generator of the present invention.

The implantation of device can use known method to carry out, for example describe in the United States Patent (USP) 7,020,531 of Colliou etc. licensing to, its at this by with reference to introducing.Colliou, et al. has instructed adhering to of functional device and coat of the stomach, and the device of coat of the stomach electricity irritation for example is provided.At necessity place, similar or diverse ways can be used to connecting device to other other position of stomach.

About Fig. 4, according to concrete scheme of the present invention, illustrate typical electrical voltage/current profile figure, simulation, stimulation, enhancing, the blocking-up of the one or more parts that are applied to gastrointestinal tract and/or gastrointestinal tract nerve is described and/or regulates electric pulse.

With reference to figure 4, can utilize that electric pulse generator 310 realizes that suitable being used to is simulated, stimulated, electrical voltage/current profile Figure 40 0 of enhancing, blocking-up and/or regulating impulse 410, described pulse 410 is applied to the part 200A of gastrointestinal tract and/or gastrointestinal tract nerve, and for example vagus nerve 200.In a preferred concrete scheme, electric pulse generator 310 can combine with power supply 320 and control unit 330, described control unit 330 has, for example, processor, clock, memory or the like, to produce train of pulse 420 to electrode 350, described electrode 350 transmits simulation, stimulation, enhancing, blocking-up and/or regulating impulse 410 via lead 340 neurads 200.

The parametric optimization of conditioning signal 400 is programmable, for example frequency, amplitude, duty cycle, pulse width, impulse waveform or the like.With regard to the ESDD device of implanting 300, the programming of control unit 330 can occur in before or after the implantation.For example, the ESDD device 300 of implantation can have receptor 360, is used for communication setting between ESDD device 300 and programming unit 370.Programming unit 370 can comprise the external communication device, improves treatment with the programming that changes ESDD device 300.

Pulse signal 410 preferably has the selecteed frequency that influences therapeutic outcome, amplitude, duty cycle, pulse width, impulse waveform or the like, promptly simulates, stimulates, strengthens, blocks and/or regulate the part or all of sensation transmission of satiety and hunger sensation.Conditioning signal can have the selecteed pulse width that influences therapeutic outcome, for example about 20 μ S or bigger, and for example about 20 μ S are to about 1000 μ S.Conditioning signal can have the selecteed peak voltage amplitude that influences therapeutic outcome, for example about 1mV or bigger, and for example about 1mV is to about 2V.

According to another concrete scheme, ESDD device 300 of the present invention can be provided by the type with " pacemaker ", wherein electric pulse 410 is produced the selection zone 200A of gastrointestinal tract and/or gastrointestinal tract nerve in a periodic manner by ESDD device 300, for example bottom section and/or vagus nerve 200, go up tonal signal with the hypoergia of in the patient, creating tissue or nerve, or suitable electric pulse suppresses to organize or neural reactivity to stimulating to give.

Yet; concerning all situations of permanent implantation; implanting the surgeon should change by the signal of control unit 330 adjustings and the specific site of electrode 350; up to the result who realizes expectation; and should monitor the long term maintenance situation of this effect, can not offset expected effect with the adaptation mechanism of guaranteeing patient body.

According to preferred embodiment of the present invention, electronic stimulation can utilize cell winding and treatment coil to realize, its catch with the natural signals of store patient (signal that the patient forms, PGS).Little coil is normally used for the purposes of perception.As mentioned above, depend on the environment of treatment, the natural signals that coil can be used to not only perception but also regulate the patient, and under other environment, independent treatment coil or electrode can be preferred.If the effect of perception and adjusting will be carried out simultaneously, it can be preferred dividing other perception and treatment coil.For implantation, coil is preferably little, shown in Fig. 5 A and 5B, and on the flexible substrate that can in the silicones of implanting level or other materials, hide.

Fig. 5 A and 5B illustrate exemplary complex copper micro-coil used according to the invention 500 and its feature.As shown, each typical coil 500 has the length of overall width and the 4.24mm (0.167 ＂) of 2.3mm (0.090 ＂).Each coil 500 has 44 circles 510.For each induction system, for example electrode 350, always have 176 circles, have the stacked and string of 4 coils 500 around.Diagrammatic conductor width 520 is 12.5 microns (0.0005 ＂), and the interval between the diagrammatic conductor 530 also is 12.5 microns.Diagrammatic conductor height 540 is 7 microns (0.0003 ＂).Each of 4 copper conductor layers can be separated by 10 microns (0.0004 ＂) thick polyimide layer.

Accurately in detail wire size, the number of turns and the geometry of selecting cell winding 500 of the present invention with can perception from the signal of 10-1000Hz and 1mV to 2V.Microprocessor in control unit 330 can use analog digital conversion (A/D) transducer to come digitized signal and can store the highest 500 seconds signal in memory (1MB memory) by 2000 samples/sec or higher speed.When needs, sort signal can be taken out and be delivered to digital-to-analogue conversion (D/A) transducer from memory with identical speed, enlarges and is applied to the patient by treatment coil 500 and/or electrode 350.Other background information can be at United States Patent (USP) 6,564,101 and U.S. Patent application 20050222637 in find, aforesaid both is by with reference to introducing (its copy is enclosed).

Perception of the present invention aspect can utilize known cognition technology, for example describes in the United States Patent (USP) 5,861,014 that licenses to Familoni, and it is introduced by reference at this.Familoni discloses the implantable pulse generator that is connected and has pick off with gastric system, be used for perception unusual at gastric electrical activity, and the detection meansigma methods, be used for detecting that unusually for example stomach is arythmia, bradygastria, dysrhythmia, tachygastria, backflow or decompose.If any of these stomach allorhythmia is detected, then pulse generator emission boost pulse string is treated detected stomach allorhythmia to gastric system.

About Fig. 6, illustrate the flow chart of the typical implementation 600 of the concrete scheme of the present invention.Connecting line is only to be used for illustration purpose, rather than is used to limit function of the present invention or hints specific event sequence.Many action can be much occurring in sequence, and do not have specific order.

Consider patient's feature (sex, age, body weight, height, health status or the like), ESDD device 300 can be implanted to (action 610) expection of patient can obtain the gastrointestinal region of best possible outcome.After ESDD device 300 was implanted to the patient, user 380 (patient, doctor, healthcare attendant or the like) can operate programming unit 370, with programming (action 620) control unit 330.

Depend on the configuration of ESDD device, user 380 can import (action 622) various data points when incident takes place, and comprises meal time, the size of dining persistent period, type and meal, the content of eating or the like.In addition, when the patient felt to influence the sensation of food ration, user 370 (if not the patient, so with the patient) can trigger (action 624) programming unit 370, to detect or sensation that the perception patient feels and can import (action 626) type of impression and the sensation intensity of perception.Sensation can comprise hunger sensation, satiety, stomach satiety, the empty sense of stomach stomach function regulating pain.These data points comprise patient's perception of various specific sensation variablees, for example modality of sensation, sensation time, persistence of sensation time and sensation intensity.Control unit 330 can record patient perception, for example be used for the modeling signal.Control unit 330 also can be programmed, with the signal (PGS) relevant with this sensation of sensation patient formation, as automatic trigger.

When triggering, ESDD device 300 begins to detect (action 630) PGS by electrode 350 and/or lead 340, and signal form is stored (action 632) in control unit 330.With the data about modality of sensation and intensity of user 380 input, control unit 330 can make the modality of sensation of input and the PGS signal form of storage set up contact, as the part of the PGS of modeling (action 634) given sensation and intensity.

Based on predetermined programming mode or user program pattern, control unit 330 can utilize sensor element to monitor the electroactive of (action 640) stomach intestinal tissue and/or gastrointestinal tract nerve, with the perception various PGSs relevant with the sensation that influences food ration.When the controlled unit of the PGS relevant with the sensation that influences food ration 330 detects (action 642) then, control unit 330 can use (action 644) electric pulse with simulation, stimulate, strengthen, blocking-up and/or regulate PGS.When suitable the time, control unit 330 does not produce action.

For example, when detecting hungry PGS in the slimming patient of needs, control unit 330 can be used electric pulse and block or reduce hungry PGS, uses electric pulse and simulates satiety PGS, or use both simultaneously.Use intensity, the persistent period of electric pulse and regularly can programme in advance, influenced by user program, or simultaneously both.As embodiment, the user can be prompted whether will use electric pulse; Time delay can be integrated with in the programming; To be programmed with the time of patient's diet every day, so that the hungry PGS of suitable time is unaffected.

User's (action 628) control unit 330 of programming is in many ways for example adjusted the application and the intensity of hungry relevant or full abdomen coherent pulse.For example, although at environment, for example under the situation that a small amount of back patient that has meal continues to feel hungry, the user can programming Control unit 330 comes satisfy abdomen PGS (it will stimulate or strengthen the signal of existence) and/or block the pulse of hungry PGS of application simulation.On the contrary, feel that too full patient can block or reduce full abdomen PGS to use electric pulse in programming Control unit 330.According to the interval between having meal, control unit 330 can be used the PGS that electric pulse strengthens detection, keeps satiety in the slimming patient of needs, or promotes hungry in needing the patient of weight increase.

Although the device configurable limit will be limited to the feature of electric pulse, particularly control unit is with applicable frequency and amplitude, but the device configurable limit also can be suitable for outside the pulsating sphere of patient treatment, therefore BSDD device 300 can have the treatment restriction that is pre-programmed in the control unit 330, makes user 380 not surmount.

ESDD300 also can have the default settings of pre-programmed, and described default settings can be by leading subscriber 390 (action 650), and for example the doctor selects, to be suitable for various patient characteristics and to implant configuration.Leading subscriber 390 can exercise administrative rights, for example, by based on the role to the inlet of programming unit 370 or by administrative unit, programming unit 370 PC that can connect for example.

Depend on the configuration of ESDD device 300, momentarily, leading subscriber 390 can be downloaded (action 652) data from control unit 330 or programming unit 370 in addition, with monitoring patient's progress be used for looking back and revising therapeutic scheme.As above, it is own that download can occur in programming unit 370, allows leading subscriber 390 directly to look back data on programming unit 370, if for example programming unit 370 is situations of personal digital assistant (" PDA ").Alternatively or additionally, download can be to administrative unit, for example is used to the purpose of filing.Similarly, according to circumstances, leading subscriber 390 can be adjusted or refuse (action 654) various programmings and data by user's 380 inputs.

The description though the specific concrete scheme of the present invention's reference has been come in is appreciated that these concrete schemes only are used to illustrate principle of the present invention and application.Therefore be appreciated that when not departing from the spirit and scope of the invention that defines by claim, can do many modifications and can design other schemes illustrative concrete scheme.

Claims (10)

1, a kind of method comprises:

According to the information that provides by the patient, quantitatively one or more sensations about patient's gastrointestinal tract by patient's identification;

The activity of at least one of perception patient's stomach intestinal tissue and gastrointestinal tract nerve;

With patient's gastrointestinal tract relevant feel of the activity of the stomach intestinal tissue of perception and/or gastrointestinal tract nerve with patient's identification associated;

Active and the association between them of the sensation of store patient identification, perception;

After this, based on further perception patient's the stomach intestinal tissue and/or the activity of gastrointestinal tract nerve, measure the existence of the impression relevant of one or more patient's identifications with patient's gastrointestinal tract; With

Use the one or more selections zone of at least one electric pulse to patient's gastrointestinal tract, with simulate, stimulate, strengthen, block and regulate patient's gastrointestinal tract tissue and/or gastrointestinal tract nerve active at least one, change the sensation about patient's gastrointestinal tract of patient impression.

2, method as claimed in claim 1, wherein the change about the impression of patient's gastrointestinal tract by patient impression is a desire treatment eating disorder.

3, method as claimed in claim 2, wherein eating disorder comprises overfeeding, overweight, fat and undereating at least one.

4, method as claimed in claim 1 wherein feels to take from the group of being made up of following by patient identification: the satiety of hunger sensation, satiety, stomach, the empty sense of stomach stomach function regulating pain.

5, the method for claim 1, wherein the perception activity of patient's gastrointestinal tract tissue and/or gastrointestinal tract nerve is to take from the group of following composition: one or more ramose one or more nerves of one or more nerves of one or more nerves of one or more muscle of patient's gastrointestinal tract, domination patient's gastrointestinal tract, the one or more nerves at the bottom of the domination patient stomach, a domination patient left side and right vagal end branch and domination patient solar plexus.

6, the method for claim 1 is to automatically perform according to the measurement to the impression of one or more patients' identifications of existing to one or more at least one electric pulse of selection area applications of patient's gastrointestinal tract wherein.

7, method as claimed in claim 6, wherein the automatic application of at least one electric pulse stands at least one of time delay and predetermined time interval.

8, method as claimed in claim 6, wherein the automatic application of at least one electric pulse stands patient's reinforcement and at least one of refusal.

9, a kind of system comprises:

The input element that is used to the information that receives, described information are to come quantitatively one or more sensations about patient's gastrointestinal tract by patient's identification according to the information that is provided by the patient;

Induction element is used at least one activity of perception patient's gastrointestinal tract tissue and gastrointestinal tract nerve;

Treatment element is used for patient's gastrointestinal tract relevant feel of the activity of the stomach intestinal tissue of perception and/or gastrointestinal tract nerve with patient's identification associated;

Memory cell is used for the sensation of store patient identification, the active and association between them of perception;

Treatment element is used for subsequently based on further perception patient's the stomach intestinal tissue and/or the activity of gastrointestinal tract nerve, measures the existence of the impression relevant with patient's gastrointestinal tract of one or more patients' identifications; With

Driving element, be used to use the one or more selections zone of at least one electric pulse to patient's gastrointestinal tract, with simulate, stimulate, strengthen, block and regulate patient's gastrointestinal tract tissue and/or gastrointestinal tract nerve active at least one, change the sensation that the patient feels about patient's gastrointestinal tract.

10, a kind of device comprises:

Electric pulse generator;

The power supply that links together with electric pulse generator;

The control unit that communicates with electric pulse generator and link together with power supply;

The electrode that links together with electric pulse generator; With

The electrode cable or the coil that link together with electrode are for attachment at least one one or more selections zone of patient's gastrointestinal tract tissue and gastrointestinal tract nerve;

Wherein control unit is operable as:

Reception information, described information are to come quantitatively one or more sensations about patient's gastrointestinal tract by patient's identification according to the information that is provided by the patient;

From electrode cable and coil, the activity of the patient's of reception perception stomach intestinal tissue and at least one of gastrointestinal tract nerve;

With patient's gastrointestinal tract relevant feel of the activity of the stomach intestinal tissue of perception and/or gastrointestinal tract nerve with patient's identification associated;

Active and the association between them of the sensation of store patient identification, perception;

Subsequently, based on further perception patient's the stomach intestinal tissue and/or the activity of gastrointestinal tract nerve, measure the existence of the impression relevant of one or more patient's identifications with patient's gastrointestinal tract; With

Cause electric pulse generator to pass through electrode cable or coil, use the one or more selections zone of at least one electric pulse to patient's gastrointestinal tract, with simulate, stimulate, strengthen, block and regulate patient's gastrointestinal tract tissue and/or gastrointestinal tract nerve active at least one, change the sensation that the patient feels about patient's gastrointestinal tract.

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