JP2008272503A - Device for infusing insulin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a device for delivering insulin to a subject with impaired hepatic glucose processing. <P>SOLUTION: The device delivers a series of pulses of insulin to the subject accompanied by ingestion of glucose in the form of a carbohydrate containing meal. The amount of insulin in each pulse, the interval between pulses and the amount of time to deliver each pulse to the subject are selected so that initially after ingestion of the carbohydrate containing meal, the subject's circulating blood glucose level rises, and then an amount as much as not lower than 50 mg/dL falls. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a device for injecting insulin, and more particularly to a device for delivering insulin to a patient suffering from senile dementia.

Diabetic retinopathy is a leading cause of blindness. Although significant advances in early detection and laser treatment have significantly affected this chronic complication of diabetes, the number of diabetic patients with diabetic retinopathy is still increasing.
Glucose control is typically measured in a blood test, which determines the level of hemoglobin A1 _c that has been the result of a desired insulin treatment in a diabetic patient for many years. However, it is clear that more than 25% of the study participants who protected strict circulating glucose control from the onset or progression of diabetic retinopathy or diabetic peripheral neuropathy were inadequate.
The main cause of death in diabetic patients is various forms of cardiovascular disease. Existing evidence indicates that it is particularly sensitive to heart failure, mainly associated with coronary atherosclerosis and autonomic neuropathy. There is little doubt that metabolic components are present in various forms of cardiovascular disease in diabetics. Cardiac dysfunction often developed in diabetics (low stroke volume, cardiac index and ejection fraction, high left ventricular end-diastolic blood pressure) can be explained at least in part by metabolic abnormalities It is considered secondary to insulin deficiency, as proper insulin administration can restore the normal pattern of cardiac metabolism (Avogaro et al., Am J Physiol 1990, 258: E606-18).

The pathophysiology of diabetic nephropathy is only partially understood. The most consistent morphological finding in diabetic nephropathy is mesangial swelling, which can compress glomerular capillaries and alter intraglomerular hemodynamics.
Diabetes is the primary cause of atraumatic amputation. A common cause of amputation is a wound that does not heal and progresses to necrosis or gangrene. In general, it is recognized that diabetics are very difficult to cure and overcome infections. In general, diabetes, especially poor circulating glucose control, is thought to be causally related to poor wound repair in diabetic patients, and is also a cause of lack of energy and general fatigue.

  Diabetes mellitus and the risk of dementia A. Ott, PR. Stolk, F. Van Harskamp, The Rotterdam Study, Neurology, 1999, vol. 53, pp. 1937-1942 The risk of developing is high. Having diabetes almost doubles the risk of developing dementia (risk is 1.9 times higher). Similarly, the risk of diabetics with Alzheimer's disease is almost doubled. And in diabetic patients inoculated with insulin, there is a four-fold greater risk than in non-diabetic patients. These findings remained unchanged even after considering the effects of gender, age, education level and other measured factors. Therefore, it can be concluded that diabetes is a risk factor for the development of dementia, including Alzheimer's disease.

What is needed is to restore metabolism, enhance pyruvate dehydrogenase activity, enhance retinal glucose and nerve glucose oxidation, treat retinopathy and central nervous system diseases, increase stroke volume By improving the cardiac index, increasing ejection fraction, lowering ventricular end-diastolic blood pressure, thereby improving cardiac function and improving quality of life in diabetic patients is there. There is also a need for similar devices that significantly reverse cardiac dysfunction common to diabetics with heart disease. The apparatus must also be able to improve blood glucose control as measured by hemoglobin A1 _c. Furthermore, the overall metabolic process is improved by the multiplicity of effects on neurovascular reactivity, intraglomerular pressure and hemodynamics, suppressing the progression of overt diabetic nephropathy, and suppressing intraglomerular hemodynamics to diabetic nephropathy There is also a need for a similar device that suppresses progression and reduces the risk of developing ESRD. In addition, it enhances glucose oxidation in the affected area, thus consuming a small amount of oxygen to treat the wound, providing a large amount of energy, promoting healing, and lower limb amputation for both diabetic and non-diabetic patients. There is a need for similar devices to avoid. There is a need for a device that improves metabolism in the brain of diabetic patients suffering from one of the many diseases that cause senile dementia and improves the mental function of patients suffering from senile dementia. .

  US Pat. No. 4,826,810, which is incorporated herein by reference, describes a method of delivering an insulin pulse to a patient after oral intake of a carbohydrate-containing diet. This insulin pulse is adjusted to produce a series of peaks in free insulin concentration and to continuously increase the minimum value of free insulin concentration between those peaks. In order for this method to be a viable treatment for clinical purposes, there must be an accurate level to determine the peak and ensure that the ingested carbohydrate processing capacity in the patient's liver is activated. Therefore, there is a need for a simple and inexpensive method for measuring free insulin in order to ensure the above. The only viable method of measuring “free” insulin is expensive and time consuming, ie often requires several days to obtain a result. On the other hand, it is not known whether the liver is activated. What is needed is a method that can determine that the patient's liver has actually been activated in real time while the pulse is administered and the baseline of free insulin is rising.

The present invention provides a device for delivering insulin to patients with impaired hepatic glucose processing. The device delivers a series of pulses of insulin to the patient at the time associated with oral intake of glucose in the form of a carbohydrate-containing meal. The amount of insulin in each pulse, the interval between pulses, and the time to send each pulse to a subject such as a patient are selected so that hepatic glucose processing is restored in the patient. At the beginning of an oral intake of a carbohydrate-containing diet, the patient's circulating blood glucose level increases.
A first pulse for insulin delivery is administered at the same time or soon after the circulating glucose level increases in the patient. This pulse results in a peak “free” insulin concentration in the blood shown in FIG. Up to Y, when the second pulse is administered when about 90% “free” insulin concentration falls, it rises to peak F. When the “free” insulin concentration drops again by about 90% to Z, the next pulse is administered. Thereby, it rises to the peak G. By repeating this process, a “free” insulin concentration between the peaks indicated by the straight line H results. The pulses are controlled so that the “free” insulin concentration between peaks increases from 10 to 500 μunits / ml from one pulse to the next. To activate the liver, it is necessary to increase the peak “free” insulin concentration after oral intake of a carbohydrate-containing diet to reduce circulating blood glucose levels by 50 mg / dl in patients with impaired hepatic glucose handling. is there. However, even if the “free” insulin level between peaks increases, it often happens that the level does not rise fast enough to activate the liver. In such situations, the decrease in circulating glucose does not reach 50 mg / dl.

  Although it is desirable to administer the minimum amount of insulin in response to activation of hepatic glucose processing, the amount of insulin required to activate hepatic glucose processing in patients varies from patient to patient and is the same It varies from day to day for patients. For the same patient on one day, pulse therapy successfully achieves activation of hepatic glucose processing, while on the next day, the same patient becomes more significantly more likely to achieve activation. Require more insulin per pulse or more frequent pulses. Measuring “free” insulin levels in the blood is an expensive and laborious method and cannot provide the necessary information in real time. In this specification, the point at which the patient actually activated hepatic glucose processing to be able to positively confirm the successful patient's response and signal when the pulse no longer needed to be administered. A method for measuring in real time is disclosed.

  In patients who have recovered hepatic glucose treatment, the circulating blood glucose level is directly reduced by 50 mg / dl or more as a result of hepatic glucose treatment recovering in the liver. This circulating blood glucose signal is readily and inexpensively available, can be performed by the patient in a home health care environment without the assistance of a doctor, and provides information on recovery of liver function in real time. Patients are usually well trained and can obtain sufficient levels of their own circulating glycoses without requiring physician assistance in maneuvering and evaluation of results. Other means of determining whether the liver is activated are expensive, do not provide information in real time, require physician evaluation, or cannot be used in a home health care environment. In a series of insulin pulses, at least two pulses need to be exceeded. For example, there are 3 pulses, 4 pulses, 5 pulses or 6 pulses. In a preferred embodiment, the device is a pump that delivers 10 series of pulses over an hour. The pump is preferably controlled by a programmable process or unit that controls the amount of insulin in each pulse, the time to deliver each pulse, and the time between pulses. Circulating blood glucose levels can be measured by any suitable circulating glucose measurement method, including fingerstick methods.

Accordingly, the present invention is an infusion device for injecting a series of insulin pulses into a diabetic patient at regular intervals. At the same time, the patient orally ingests a carbohydrate-containing diet and periodic glucose measurements are taken to ensure that proper hepatic glucose processing has been restored.
The patient consumes liquid or food-containing glucose to prevent the patient from becoming hypoglycemic. A preferred liquid or food containing glucose is 110-280 g (4-10 ounces) of GLUCOLA for diabetics to be converted to 40-100 g of glucose, including cakes and breads containing glucose Similar types of liquids or hyperglycemic foods that are not limited to can be administered to a patient. For non-diabetic patients, the amount of glucose taken orally is large and needs to be adjusted for each patient.

  In a preferred embodiment of the invention, the programmable insulin pump is programmed to deliver intravenous insulin in precisely measured pulses and programmed to deliver each pulse within a minimum amount of time. , Programmed to allow a time interval between each pulse. However, a method of injecting an accurately measured amount of insulin including simple injection with a syringe is acceptable. A preferred insulin delivery means is a programmable infusion device that can deliver accurately measured insulin pulses at scheduled intervals as long as there is enough blood glucose to prevent the patient from becoming hypoglycemic . The infusion device is also preferably capable of delivering insulin pulses in the shortest possible time without adversely affecting the vein at the infusion site used. One preferred infusion device is Bionica MD-110. However, less accurate devices, including simple syringes, and slower devices can deliver pulses and the required infusion profile.

  In an embodiment, the programmable handheld pump uses a conventional medical syringe that infuses insulin. Referring to FIG. 1, the syringe 11 is coupled to the pump by clips 13 and 14, and the plunger 15 is moved by a syringe driver 16. A syringe driver is an actuator that is driven by any of the many possible actuator settings known to those skilled in the art. A conventional infusion tube connection device can be used to connect the infusion tube to the syringe. The programmed values may be entered into the control processor by keyboard 17, by firmware in the pump, or by software via communications link 18 to a high level computer or other suitable input method. The communications link can be used to send alarms and status messages via an acceptable communications protocol and medium.

  The circulating glucose measuring device configured to directly cooperate with the pump through the communication link can appropriately provide the circulating glucose value. Separately, the wireless communications system automatically sends information from a circulating glucose sensor (not shown) such as a blood glucose meter to the pump without operator intervention. Typical circulating glucose sensors include, but are not limited to, fingerstick devices, non-intrusive devices that use near-infrared spectrum or high frequency, and implantable sensors. Alternatively, the circulating glucose signal is obtained from an implantable system for monitoring pancreatic beta cell electrical activity in the patient to measure the patient's insulin demand and circulating glucose levels. Other methods may be employed as long as the change in circulating glucose level can be accurately measured directly or indirectly. Communications links can send alarms or status messages to higher level computers via acceptable communication protocols and media.

As the pump moves, the programmed insulin pulse is dispensed to the patient at the programmed time. Insulin is delivered through the infusion tube 19 to the needle 10 and is intravenously inserted anywhere in the patient's convenience, preferably in the forearm. The time to send each pulse should be as short as possible, at least less than 1 minute, preferably on the order of seconds. Pump status, alarm status and circulating glucose level can be displayed on the display panel 12 among other system parameters.
In a preferred embodiment, the patient's circulating glucose level is measured periodically and used automatically or manually to input changes to the parameters of the pump delivering insulin. Adjustments to orally ingested glucose and infused insulin are then made to give the desired result of activating the liver without the undesirable side effects of hyperglycemia or hypoglycemia.

  In another embodiment instead of a syringe-type pump, referring to FIG. 2, the infusion pump includes a cartridge 22, a housing 24, a plunger 25, a reservoir region 27 in the cartridge containing insulin, and the cartridge with an infusion tube 21. It includes a cassette cartridge pump device comprising a neck opening for connection to an infusion needle 20 which is inserted intravenously into the forearm, preferably anywhere in the patient. The pump mechanism includes a gear linkage 26, a motor 28 and a pump device 29. When the cartridge 22 is engaged in the housing 24, the cartridge is clamped in place by rotational engagement of the cartridge male thread and the housing female thread. The cartridge is optionally made from glass, ceramic, steel or plastic. The pump mechanism is used to rotate the piston-type plungers 25 and 23 within the cassette cartridge. The pump mechanism can be actuated by a coordinated hand-eye movement or manual movement up to a series of “click” points, including but not limited to a motor that rotates the plunger or housing. The plunger is rotated relative to the cassette housing wall. As the plunger 25 rotates and rotates, the device injects insulin into the patient. Preferably, the pump mechanism is controlled by a programmable processor that controls the amount of insulin to be infused, the timing between pulses, and the length of time to inject a single pulse. The diameter of the reservoir area and the depth of the plunger that moves for each plunger rotation are chosen to give a very accurate pulse size that is delivered in the shortest possible time for safety. The programmed value may be entered into the control processor by keyboard, firmware in the pump, software via communications link 30 from a high level computer, or other suitable input method. Automatic input of blood glucose levels can be achieved as described above. The same communications link can be used to send alarms and status messages via a communications protocol and medium that is acceptable to a high level computer. The pump status, alarm status and circulating glucose level can be displayed on the display panel 12 of the pump device 29, among other system parameters.

Hepatic glucose treatment includes proper absorption of glucose in hepatocytes, oxidation of glucose by hepatocytes, storage of glucose as hepatic glycogen in hepatocytes, and conversion of glucose to fat or alanine, amino acids by hepatocytes. Liver processing is impaired if the liver does not produce the liver enzymes required for proper glucose processing, especially liver glucokinase, phosphofructokinase, or pyruvate kinase. Glucose processing disorders are a basic symptom of patients with diabetes type 1 or type 2 for patients whose pancreas does not produce enough insulin, or for patients with insufficient insulin resistance, or a combination of these factors. After glucose ingestion, hepatic glucose processing is impeded by reduced glucose oxidation, reduced alanine production, and little timely glycogen production and accumulation in the liver, even by intravenous insulin administration It is shown that. A glucose tolerance test and hemoglobin A1 _c measurement can be used as an indication that hepatic glucose processing is impaired.

  A preferred embodiment of a method of delivering an insulin pulse to a patient with long-term intermittent intravenous insulin therapy (CIIIT) is as follows. On the morning of the procedure, the patient preferably sits in a blood collection chair and a 23 gauge needle or catheter is inserted into the vein, preferably the hand or forearm, to reach the blood vessel. However, such delivery systems including indwelling catheters, PICC lines or PortaCath can also achieve the required results. After a brief equilibration, the patient is asked to make a circulating glucose measurement before actually starting the insulin infusion. The patient's circulating glucose level prior to using the infusion device is preferably close to 200 mg / dl. However, in the case of diabetes in pregnant women, the maximum circulating glucose level is kept below 180 mg / dl each time it is attempted.

  After circulating glucose is measured and the patient's circulating glucose starting level is appropriate, the patient is asked to consume a liquid or food containing glucose. The amount of glucose administered to diabetics ranges from 60-100 g glucose or 170-280 g (6-10 oz) glucora, but for people with small skeletons 40 g glucose or 110 g (4 oz) glucora It may be a degree. However, the amount of starting glucose administered to the patient may vary. In non-diabetic patients, glucose may be required than in diabetic patients, but other parameters remain the same, including those required for pulse delivery. Next, insulin pulses are administered intravenously at planned time intervals, typically every 6 minutes, although other intervals from every 3 minutes to every 30 minutes can be used. For diabetic patients, the amount of insulin in each pulse is 10-200 milliunits / kg body weight of insulin and slightly less for non-diabetic patients.

  Circulating glucose is measured as often as possible. When using a finger prick, it is recommended that the patient read every 30 minutes because it is uncomfortable for the patient. If a non-invasive method of measuring circulating glucose is used, readings can often be taken after each insulin pulse infusion. It is recommended that one to two minutes after the injection of each glucose pulse before the circulating glucose level is measured is possible. Circulating glucose levels typically rise by about 100-150 mg / dl before starting to fall. In patients who have recovered hepatic glucose treatment, circulating glucose levels drop by about 50-100 mg / dl. In patients who still have to get adequate hepatic glucose treatment, it does not drop or falls well below 50 mg / dl. A decrease in circulating glucose level signifying recovery of hepatic glucose processing is achieved approximately within 1 hour from the start of the first pulse of insulin using the preferred embodiment of the present invention, but the time required is 1 It may be shorter or longer than the time. The amount of insulin in each pulse can be reduced or the time between pulses can be increased so that it takes 2 or 3 hours or more for the 50 mg / dl reduction to occur. The longer it takes to activate the patient, the longer the patient will be treated, which is not desirable for the patient. This reduction in circulating glucose results from a combination of increased muscle glucose utilization and glucose usage by the liver.

Another indication that liver activation has been reestablished is that the amount of insulin required to reduce circulating glucose levels by 50 mg / dl gradually decreases with time. A decrease in hemoglobin A1 _c levels is an intermediate symptom that liver treatment has recovered. Long-term symptoms are seen in a reduction in many diabetes related diseases including but not limited to retinopathy, nephropathy, neuropathy, hypoglycemia, cardiovascular disease, or hypertension.
The period of administering a series of insulin pulses and ingesting glucose typically lasts 56 minutes (10 pulses at 6 minute intervals), usually followed by a rest period of 1 or 2 hours. Insulin levels increased by the rest period can return to baseline. During periods when insulin is not infused, the intravenous site preferably switches to heparin or saline lock. The entire procedure is repeated until the desired effect is obtained. Typically, the procedure is repeated 3 times on each treatment day, but can be repeated as often as twice a day or up to 8 times. In preferred embodiments, the circulating glucose level is stable at 100-200 mg / dl for about 30-45 minutes before the patient is released from the procedure, either in the clinic or in the home environment.

Thus, the present invention is an apparatus used to enhance retina or neuronal glucose oxidation by increasing pyruvate dehydrogenase activity, and thus to treat retinopathy and central nervous system disorders in both diabetic and non-diabetic patients. is there. A method for monitoring retinal or neuronal glucose oxidation is a PET (positron emission tomography) scan. It is also possible to search for stabilization / reversal of diabetic retinopathy. In terms of nerve function, peripheral neuropathy is improved and manifests as an increase in sensation, in particular an increase in sensation in the foot, and disappearance of the “burning sensation” or “feeling of tingling” in the foot pain. It also improves autonomic neuropathy, especially mild gastric atony and orthostatic hypotension.
Diabetic heart disease is one of the common complications of diabetes that affects both type 1 and type 2 patients. It is generally agreed by experts that the primary fuel for both normal and diabetic hearts is free fatty acid, a fuel that requires more oxygen per calorie than glucose as fuel. As a result, the heart is not particularly resistant to ischemia in both diabetic and non-diabetic individuals. Even a slight or temporary decrease in blood flow or oxygen supply is catastrophic if the tissues involved primarily utilize free fatty acids for energy generation. On the other hand, if the tissue oxidizes glucose from free fatty acids to produce an equivalent amount of energy, the temporary disruption of blood or oxygen supply is not detrimental because the tissue demand for oxygen is low. Thus, for the same amount of oxygen delivered to the myocardium, utilization of glucose rather than utilization of free fatty acids results in high energy (ATP) production. The device will allow more glucose to burn or oxidize and improve dietary fuel processing capacity by correcting for the use of free fatty acids associated with heart and cardiovascular disease in both diabetic and non-diabetic patients. Can do.

In addition, the present invention improves the overall metabolic process in both diabetic and non-diabetic patients by multiple effects on neurovascular reactivity, intraglomerular pressure and hemodynamics, and suppresses the progression of overt diabetic nephropathy. In addition, the device is capable of improving intraglomerular hemodynamics to suppress the progression of diabetic nephropathy and to reduce the risk of developing ESRD.
Furthermore, the present invention enhances glucose oxidation in affected areas for both diabetic and non-diabetic patients, thus providing more energy while delivering the oxygen to treat the wound and healing. It is a device that can promote and avoid cutting. The rationale for this healing improvement is that the tissue surrounding the affected area has an inadequate blood supply and thus insufficient oxygenation. If this tissue is fueled by high glucose oxidation instead of free fatty acid utilization, and therefore switched from a lipid-based fuel system to one based on glucose oxidation, the same amount of blood flow wound healing, ie delivery Much energy is available for healing from the amount of oxygen released. In addition, the ability to obtain more energy from less oxygen is also addressed for general malaise associated with diabetic individuals whose energy levels are below normal.

  In many cases, patients suffering from diabetes as well as dementia are treated with the device of the present invention. Dementia appears to be associated with inadequate metabolism of glucose in the brain, which is also a restricted flow of blood. This poor metabolism is at least partly responsible for dementia. Using the device of the present invention for patients suffering from senile dementia can improve the confusion, weakness, disorientation, cognitive function, and lack of memory associated with dementia, and improvements in glycemic control. Clearly shown. Suppressed flow to the brain is also common in demented patients who do not suffer from diabetes, and the device of the present invention provides these patients with improved metabolism and therefore suffers from diabetes It is effective in treating both demented and unaffected demented patients.

In a preferred embodiment with a new patient, three treatments are given for two consecutive days in the first week. For ongoing patients, the procedure is performed once a week. For patients who need a more thorough method, the procedure can be repeated three or more times, continuously and weekly, until the desired clinical outcome is obtained.
The following non-limiting examples are given for illustrative purposes only.

Example 1
A study was conducted to evaluate the impact of CIIIT on the progression of diabetic nephropathy in patients with type 1 diabetes (DM). This 18-month, multi-center prospective, controlled study was adopted by 49 patients with type 1 DM with nephropathy who are undergoing the Diabetes Control Complication Study (DCCT) Intensive Care (IT) method It was. Of these, 26 patients were control group C, IT continued, 23 patients were treatment group (T) and received CIIIT weekly in addition to IT. All clinical trial patients went to the clinic weekly for 18 months and examined glycated hemoglobin HbA1 _c every month and measured urinary protein excretion and creatinine clearance (CrCl) every 3 months. As expected, ClCl declined significantly in both groups, but the Tl group CrCl slope rate (2.21 ± 1.62 ml / min / yr) was C group (7.69 ± 1.88 ml / min / yr, P = 0.0343). It is concluded that when CIIIT is added to the IT of type 1 DM patients with obvious nephropathy, it is clear that the progression of diabetic nephropathy is markedly suppressed.

Example 2
A middle-aged woman with type 1 diabetes for more than 22 years suffered from polyneuropathy. She had generalized pain and could not walk or even stockings because of the pain. After being treated with this device, the pain diminished to the point where women enjoyed harsh exercises such as roller braiding.

Example 3
Middle-aged women with type 1 diabetes for more than 30 years had severe peripheral neuropathy, constant pain below the knee, and could not sleep overnight. After treating with this device, she no longer uses pain medications and has no severe pain in her lower limbs. She has been using this treatment for 8 years.

Example 4
A middle-aged woman with type 2 diabetes for 17 years had severe dilated cardiomyopathy (ejection fraction 14-19%). Treatment began with the device after she was placed on the list for a heart transplant. After receiving treatment, the patient stabilized to a point where insulin intake decreased from 150 to 24 to 26 units / day, and no longer required a heart transplant, and was actually removed from the heart transplant list. The patient has been treated for nine years and has not yet been on the heart transplant surgery list. Her ejection fraction is currently 29-32%.

Example 5
A middle-aged man with type 1 diabetes for 38 years suffered from macular degeneration (retinopathy). He could not drive at night. After treatment with this device, my eyesight recovered to the point where night driving was not a problem. The patient has been treated for 4 years.

Example 6
Middle-aged male type 2 diabetics had severe heart disease including congestive heart failure and severe arteriosclerotic heart disease. A cardiac operation was scheduled, but the surgeon refused the operation because of poor patient condition. After using this device, the doctor was convinced that he could withstand four-vessel bypass surgery. The patient had few precedents as a diabetic with his stage of heart disease and recovered normally after surgery.

Example 7
Elderly male type 2 diabetic patients had excellent circulating glucose control with intense insulin treatment including 3-4 infusions / day of subcutaneous insulin. Even so, diabetic kidney disease progressed to a point where 1500 mg of protein was released for 24 hours and the rate of increase was 500 mg / 24 hours / year. After using this device, the patient's proteinuria decreased to 600-800 mg / 24 hours. He has been using the device for five years.

Example 8
Elderly type 1 diabetics who are diabetic from age 5 years were scheduled for coronary artery bypass grafting to correct diabetic heart disease. The surgeon did not operate because she was in a state of progressive diabetic arteriosclerosis. She was scheduled for a single blood vessel transplant. After using the device, her condition was restored to the point that the doctor did twice instead of one implant. She recovered normally. She has been using the device for several years after surgery without further diminishing diabetic heart disease.

Example 9
Elderly type 2 diabetic men suffering from autonomic neuropathy have an extremely high 200/120 despite a rigorous program to regulate circulating glucose using thorough insulin therapy with 3-4 subcutaneous insulin injections daily. High blood pressure was read. As a result of using this device, his blood pressure dropped to 120/80. He has been using the device for five years.

Example 10
An elderly man with type 2 diabetes had one leg cut as a result of a diabetes-related ulcer. He developed an ulcer in the other leg that did not respond to available treatment and was at risk of losing the other leg due to amputation. As a result of using this device, the second leg ulcer healed and was saved from amputation. The patient had used the device for several years and had no further ulcers.

Example 11
Middle-aged type 1 diabetic patients developed severe ulcers in both lower limbs that did not heal with available treatments. As a result of using this device, the ulcer healed and did not rebound. The patient has been using the device for 13 years now.

Example 12
A middle-aged male type 2 diabetic patient had proliferative diabetic retinopathy with severe bleeding. Multiple photocoagulation scars made additional photocoagulation impossible. As a result of using this device, bleeding stopped, the retina did not deteriorate further, and the remaining visual acuity was maintained. The patient had used the device for 5 years, had no further bleeding and did not coagulate.

Example 13
Elderly women with type 2 diabetes had severe painful peripheral neuropathy to the point that they could not walk and used wheelchairs. After 6 months of using the device, pain stopped to the point where the wheel chair was not used. The treatment was stopped for financial reasons. As a result, the neuropathy turned up and turned up before using the wheel chair.

Example 14
Middle-aged women with type 1 diabetes had severe neuropathy. The mother was bedridden due to autonomous neuropathy before using the device two years ago. Her muscles were atrophic, unable to digest food, and nerves were dying as a result of diabetes. If she didn't have two children, she said she committed suicide. She had to quit her job, became disabled and very often unrelated to the hospital. She had a wheal on her head, causing hair loss. She had no sensation in her feet, was constantly nauseous, and could not sleep at night because of pain. She had problems with insulin absorption and tried all different ways to improve insulin absorption into the body. For years she has injected herself intramuscularly because she felt she had the best absorption of insulin. Using this device, all of the illness was reversed to the point that the obstacles were removed and used advantageously. Since then she has not been hospitalized. The feeling of numbness in her lower limbs disappeared. If she refrains from treatment for a week, she can feel her limbs return to numbness. Her acute mild stomach atony reverses and no longer suffers from symptoms. Except for using this device, she is currently not incurred medical costs.

Example 15
A 79-year-old female patient suffering from advanced senile dementia was housed in a nursing home due to excessive confusion, weakness, disorientation and lack of memory. The nursing home removed the patient from the nursing home because the nursing home did not support the exact four-shot treatment required for the patient to adjust her diabetes blood glucose. The nurse recommended Hepatic Activation. Once the patient was activated, she returned completely to an independent lifestyle. She had significant improvements in motor skills, memory, and cognitive function. Liver activation clearly showed a good effect on senile dementia.

  For all of the examples listed above, after the first few days of treatment, the patient received treatment once a week, each treatment day consisting of three insulin infusions associated with the oral intake of carbohydrates. The pump device used to infuse insulin was the Bionica MD-110 pump described in FIG. 1 that does not include a sensor for circulating glucose. Typically, 10 pulses were administered per hour, with a one hour rest period between insulin infusions. The form of carbohydrate ingestion varied from time to time, including feeding on hyperglycemic foods including but not limited to bread and cakes. The patient's circulating glucose was measured once every 30 minutes by the finger stick method currently used by most diabetics. Circulating glucose initially rose during each treatment, then dropped by 50-100 mg / dl with each series of insulin infusions, meaning that the liver was actually activated. The table below summarizes the number of insulin units for the administered pulses and the amount of glucose ingested for each series of pulses according to the above example.

^* This trial includes 23 patients in the treatment group with variable doses of insulin / pulse and variable intake glucose. In other words, it includes the general limits of what was used.

  The preferred embodiments described herein are exemplary only, and the illustrated examples include many specificities, but only illustrate some possible embodiments of the invention. Other embodiments and modifications will probably be found to those skilled in the art. The illustrated examples are to be construed as merely illustrative of some of the preferred embodiments of the present invention, the full scope of the invention being defined by the appended claims and their legal equivalents. Should be determined by.

FIG. 2 is a schematic block diagram of a programmable insulin pump programmed to deliver insulin according to the present invention using a syringe plunger type mechanism. 1 is a schematic block diagram of a programmable insulin pump with a rotating plunger mechanism and programmed to deliver insulin according to the present invention. It is a figure which shows the correlation with time and the insulin concentration in blood in a series of insulin pulses.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... Needle 11 ... Syringe 12 ... Display panel 13, 14 ... Clip 15 ... Plunger 16 ... Syringe driver 17 ... Keyboard 18 ... Communications link 19 ... Injection tube 20 ... Injection needle 21 ... Injection tube 22 ... Cartridge 23 ... Plunger 24 ... Housing 25 ... Plunger 26 ... Gear linkage 27 ... Reservoir area 28 ... Motor 29 ... Pump device 30 ... Communications link

Claims (6)

A device for delivering insulin to a patient suffering from senile dementia,
A circulating glucose level measuring device for measuring the level of circulating glucose, which measures the increase in circulating glucose level from a predetermined level associated with oral intake of a carbohydrate-containing diet and results from intravenous infusion of a series of insulin pulses A device for measuring the subsequent decrease in circulating glucose levels;
Insulin delivery means for injecting insulin in a series of pulses;
A controller that activates the insulin delivery means such that upon receiving a detection output indicating an initial rise in circulating glucose level associated with oral intake of the carbohydrate-containing food, the circulating glucose level drops by an amount of 50 mg / dl or more; ,
A device characterized by comprising:   The apparatus of claim 1 wherein the amount of insulin in each pulse is about 10-200 milliunits / kg body weight.   The apparatus of claim 1, wherein the controller controls the amount of insulin in each pulse, the time interval between pulses, and the time to send each pulse to the patient.   The apparatus of claim 1, wherein the series of pulses is sent for 6 to 180 minutes.   The apparatus of claim 1, wherein each pulse of the series of pulses is sent every 3 to 30 minutes.   The apparatus of claim 1, wherein the carbohydrate-containing food contains 40-100 g of glucose.

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