Anesthetic nerve blocks and techniques

Abstract

Improved nerve blocks and methods of anesthesia are provided. [Solution] An anesthetic nerve block includes a dispenser including a storage body, a transfer body, and a tip for positioning adjacent to a nerve. A local short-acting anesthetic agent is within the storage body. A physiological carbonate base is within the storage body. The local short-acting anesthetic agent and the physiological carbonate base are provided from the tip of the dispenser. Wherein the local short-acting anesthetic agent functions with the physiological carbonate base to permeate through the nerve membrane to the axon. A local long-acting anesthetic agent is within the storage body. The local long-acting anesthetic agent is dispensed from the tip of the dispenser and permeates through the nerve membrane to the axon. The local long-acting anesthetic agent and the physiological carbonate base form a precipitated or deposited and crystallized compound to produce a long-lasting local nerve block.

Description

[Technical field]

[0001] This invention relates to the art of pain relief and, more particularly, to improved anesthetic nerve blocks and methods. [Background technology]

[0002] Authorizing prescriptions for opioids is the primary gateway to opioid addiction, which is associated with 350,000 deaths worldwide due to opioid overdoses. This invention demonstrates a technique to replace opioids for pain relief with nerve blocks that could replace the need for opioid medications following surgery or trauma.

[0003] The recent worldwide focus on opioids is to provide patients with a non-addictive solution for post-operative pain relief after surgery, trauma, and other painful episodes. Many peripheral nerve blocks (PNBs) performed by anesthesiologists have shown us that such nerve blocks are viable and effective in managing pain without the need for addictive opioid drugs.

[0004] Pain studies have shown that sharp pain (A-delta fiber) largely subsides within 48 hours after minor abdominal surgery. Even diffuse inflammatory pain (C fiber) generally subsides after 120 hours in such procedures. Thus, the goal is to provide pain relief that is sustainable for 120 hours after surgery, eliminating the need for opioid prescriptions.

[0005] Unfortunately, pain relief after such procedures with peripheral nerve blocks (PNBs) is classically limited to 24 hours or less, depending on the local anesthesia used for the block. 2Some contain agonists (clonidine, dexmedetomidine, etc.), steroids, and even epinephrine, although the duration is only longer than with local anesthesia alone. Even the longest acting local anesthesia, with a wide variety of adjuvants, rarely lasts more than 24 hours in a peripheral nerve block (PNB). The following patents and publications are representative of the antecedents of what became the trigger pump technology:

[0006] U.S. Patent No. 4,695,576 to Ikenstan discloses the local anesthetic LNn-propyl pipecolic acid, which is prepared by chlorinating L-pipecolic acid to obtain an acid chloride, L-pipecolic acid chloride, which is then reacted with 2,6-xylidine to obtain L-pipecolic acid-xylidide, which is then propylated to obtain LNn-propyl pipecolic acid-2,6-xylidide, which is a potent anesthetic with relatively low toxicity in humans.

[0007] US Patent No. 5,192,527 to Abramsohn teaches a method for controlling the duration of local anesthesia and discloses a reagent system or kit for inducing and limiting the duration of local anesthesia.

[0008] No. 5,777,124 to Zavare et al. discloses a method for preparing levobupivacaine, racemic bupivacaine or other N-alkyl analogs thereof, which comprises treating pipecolic acid hydrochloride with chlorine, amidating the resulting pipecolic acid chloride hydrochloride with 2,6-dimethylaniline in a solvent without isolation, and alkylating the resulting pipecolic acid 2,6-xylidide. Alternatively, the amidation can be carried out after the alkylation.

[0009] U.S. Patent No. 5,849,763 to Bardsley et al. discloses levobupivacaine [(S)-1-butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide], which is useful as an anesthetic, particularly in patients with CNS deficiencies or susceptible to CNS side effects. It is also useful as an obstetric anesthetic.

[0010] US Patent No. 5,919,804 to Jennery teaches levobupivacaine for providing anesthesia or analgesia during and after facial surgery in humans, particularly in dentistry or ophthalmology.

[0011] No. 5,945,435 to Evetz shows levobupivacaine particularly suitable for use in anesthetizing human patients prior to surgery that does not require hospitalization for more than 12 hours after motor blockade. Because of its advantageous motor / sensory blockade, levobupivacaine can be used for "day care" surgery.

[0012] No. 5,955,479 to Bardsley et al. teaches the use of levobupivacaine in treating chronic pain in a patient. The levobupivacaine used in the method is substantially free of dexbupivacaine. The patient may suffer from pain, for example, from heart failure, central nervous system injury, or cancer.

[0013] US Patent No. 6,019,994 to Ivetz et al. discloses levobupivacaine or ropivacaine for use in treating migraine headaches.

[0014] US Patent No. 6,069,155 to Mather et al. discloses a method for anesthetizing a human patient prior to major surgery, which comprises administering to the patient at least 200 mg of levobupivacaine.

[0015] Dyer et al., U.S. Patent No. 6,156,900, discloses a process for obtaining optically enriched pipecolic acid as a salt using an optically active acid, which process consists of the asymmetric conversion of pipecolic acid as a racemate enriched in the opposite enantiomer to that desired with an optically active acid in a solvent containing an acid that causes racemization in the absence of an aldehyde.

[0016] U.S. Patent No. 8,828,452 to Abramsohn discloses a method for providing post-operative pain control or relief to a patient. The method includes administering bicarbonate to a site on the patient, for example, during a surgical or dental procedure, when the surgical or dental procedure is nearly completed, or immediately after the surgical or dental procedure, either at a site previously administered or at a site containing regional or local anesthesia in an amount sufficient to provide pain control or relief to the patient for a period of time following the surgical or dental procedure.

[0017] Dyer et al., WO 1996 / 028426, show that optically enhanced N,O-dialkyl pipecolic acids are useful in the preparation of levobupivacaine and related analgesics. They can be readily obtained by dialkylation of optically enhanced pipecolic acid by reaction with an alkylating agent in the presence of a base and a polar aprotic solvent.

[0018] While the above-mentioned patents have contributed to advances in the technology, there remains a need for a long-lasting local anesthetic agent, i.e., a need for post-operative and traumatic pain relief for 120 hours or more, thereby greatly reducing the need for prescription opioids for these conditions.

[0019] Accordingly, one object of the present invention is to provide an improved anesthetic nerve block that represents a substantial advancement in the art.

[0020] Another object of the present invention is to provide an improved anesthetic nerve block that is easily delivered.

[0021] Another object of the present invention is to provide an improved anesthetic nerve block which can be rapidly delivered.

[0022] Another object of the present invention is to provide an improved anesthetic nerve block which can be delivered to the living body with less risk of harm.

[0023] Another object of the present invention is to provide an improved anesthetic nerve block which can be modified to vary the duration of the nerve block.

[0024] The foregoing has outlined some of the objects associated with the present invention. These objects can be understood through the illustrative examples which illustrate the features and applications associated with the present invention. Many other advantages can be obtained by modifying the present invention within the scope of the inventive concept. Thus, further objects of the present invention can be better understood by reference to the following detailed description including the summary of the invention and the preferred embodiment, together with the inventive concept defined in the claims taken in conjunction with the accompanying drawings. Summary of the Invention

[0025] The invention is defined by the appended claims, with specific embodiments shown in the accompanying drawings. In summary, the invention comprises an improved anesthetic nerve block for interrupting nerve electrical potentials and relieving pain within a living body. The nerve has an axon surrounded by a nerve membrane. The anesthetic nerve block comprises a dispenser including a storage body, a transfer body, and a tip for positioning adjacent to the nerve. A local short-acting anesthetic agent is within the storage body. A physiological carbonate base is within the storage body. The local short-acting anesthetic agent and the physiological carbonate base are provided from the dispenser tip, where the local short-acting anesthetic agent functions to permeate through the nerve membrane to the axon with the physiological carbonate base. A local long-acting anesthetic agent is within the storage body. The local long-acting anesthetic agent is dispensed from the dispenser tip and permeates through the nerve membrane to the axon. The local long-acting anesthetic agent and the physiological carbonate base form a precipitated or deposited and crystallized compound to produce a long-lasting local nerve block.

[0026] In one embodiment of the invention, the local short-acting anesthetic is lidocaine.

[0027] In another embodiment of the invention, the local short acting anesthetic is selected from the group of bupivacaine, levobupivacaine, ropivacaine and tetracaine.

[0028] In another embodiment of the present invention, the physiological carbonate base is selected from the group of sodium bicarbonate, sodium carbonate and sodium hydroxide.

[0029] In another embodiment of the invention, a local short-acting anesthetic is in the storage body. A steroid is in the storage body. The local short-acting anesthetic and steroid are provided or dispensed from a dispenser tip, where the local short-acting anesthetic functions with the steroid to penetrate the nerve membrane to the axons. A local long-acting anesthetic is in the storage body. The local long-acting anesthetic is dispensed from the dispenser tip and penetrates the nerve membrane to the axons. The local long-acting anesthetic and steroid form a precipitate or deposit and crystallize compound to produce a long-lasting local nerve block.

[0030] In another embodiment of the present invention, the steroid base is selected from the group of dexamethasone, betamethasone and triamcinolone.

[0031] The invention further comprises a method of producing an anesthetic nerve block, which interrupts the electrical potential of a nerve to relieve pain in vivo. The nerve has an axon surrounded by a nerve membrane. The method includes the steps of dispensing a local short-acting anesthetic from a dispenser and positioning the local short-acting anesthetic adjacent to the nerve. Dispensing a physiological carbonate base from a dispenser and positioning the physiological carbonate base adjacent to the nerve, where the local short-acting anesthetic acts to permeate through the nerve membrane to the axon with respect to the physiological carbonate base. Dispensing a local long-acting anesthetic from a dispenser and positioning the local long-acting anesthetic adjacent to the nerve, where the local long-acting anesthetic permeates through the nerve membrane to the axon, and the local long-acting anesthetic and the physiological carbonate base form a precipitated or deposited and crystallized compound to produce a long-lasting local nerve block.

[0032] In another embodiment of the invention, the method includes the steps of dispensing a local short-acting anesthetic agent from a dispenser and positioning the local short-acting anesthetic agent adjacent to a nerve; dispensing a local long-acting anesthetic agent from a dispenser and positioning the local long-acting anesthetic agent adjacent to a nerve; dispensing a physiological carbonate base from a dispenser and positioning the physiological carbonate base adjacent to the nerve, where the local short-acting anesthetic agent functions to permeate through the nerve membrane to the axon with the physiological carbonate base; and where the local long-acting anesthetic agent permeates through the nerve membrane to the axon and the local long-acting anesthetic agent and the physiological carbonate base form a precipitated or deposited and crystallized compound to produce a long-lasting local nerve block.

[0033] The above is a rather broad description of the important features related to the present invention. The detailed description that follows will provide a better understanding and a fuller appreciation of the present invention's contribution to the art. Additional features of the present invention are described below, which form part of the inventive concept as set forth in the claims. Those skilled in the art will be able to achieve the same objectives of the present invention by modifying or designing other configurations based on the concepts and specific examples shown herein. Those skilled in the art will also appreciate that such equivalent configurations do not depart from the spirit and concept of the invention as set forth in the claims. [Brief description of the drawings]

[0034] For a fuller understanding of the features and objects of the present invention, reference should be made to the following detailed description taken in conjunction with the accompanying drawings. [Figure 1] FIG. 1 is a side view of an organism with a sciatic nerve using an anesthetic nerve block solution for pain relief. [Diagram 2] FIG. 2 is an enlarged cross-sectional view of the sciatic nerve of FIG. 1. [Diagram 3] FIG. 3 is an enlarged portion of FIG. [Figure 4] FIG. 4 is a perspective view of FIG. [Diagram 5] FIG. 5 is a cross-sectional view of FIG. [Figure 6] Similar to FIG. 3, showing myelinated neurons (Aδ fibers). [Figure 7] FIG. 7 is an enlarged portion of FIG. [Figure 8] Similar to FIG. 3, showing unmyelinated neurons (C fibers). [Figure 9] FIG. 9 is an enlarged portion of FIG. [Figure 10] FIG. 5 is a view similar to FIG. 4, showing injections of lidocaine and NaHCO3 / Na2CO3 (possibly adjuvant). [Figure 11] FIG. 11 is a cross-sectional view of FIG. [Figure 12] FIG. 11 is a view similar to FIG. 10 showing bupivacaine carbonate precipitation. [Figure 13] FIG. 13 is a cross-sectional view of FIG. [Figure 14] FIG. 13 is a similar view to FIG. 12 showing a node of Ranvier with extra-axonal deposits of bupivacaine carbonate precipitate. [Figure 15] FIG. 15 is a cross-sectional view of FIG. [Figure 16] FIG. 15 is an enlarged portion of FIG. [Figure 17] FIG. 1 is a side view of a first embodiment of a dispenser for delivering an anesthetic nerve block solution. [Figure 18] FIG. 2 is a side view of a second embodiment of a dispenser for delivering an anesthetic nerve block solution. [Figure 19] FIG. 18 is an enlarged portion of FIG. [Figure 20] FIG. 13 is a side view of a third embodiment of a dispenser for delivering an anesthetic nerve block solution. [Figure 21] FIG. 21 is an enlarged portion of FIG. [Figure 22] FIG. 13 is a side view of a fourth embodiment of a dispenser for delivering an anesthetic nerve block solution. [Diagram 23] FIG. 1 is a flow diagram of a first method for delivering an anesthetic nerve block solution. [Figure 24]1 is a flow diagram of a second method for delivering an anesthetic nerve block solution.Like reference numerals refer to like parts throughout the several views of the drawing. Detailed Description

[0035] FIG 1-24 relates to an improved nerve block and method of anesthesia. Referring to FIG 1-9, a peripheral stimulus, such as a pinprick in the arm or leg, travels up the accessory nerve to the spinal cord before being transmitted to the brain where the stimulus is perceived. This nerve electrical impulse from the periphery to the brain is obtained by depolarizing sodium / potassium potentials across the nerve membrane (the outer membrane that covers the axon) 54 in the axon 24. These action potentials 56 in nerve firing are the result of a series of depolarizations that flow from the periphery to the spinal cord in the conduction of the nerve impulse.

[0036] Such depolarizations flow from one 20th node of Ranvier to the next in myelinated nerve fibers, as shown in Figures 6 and 7. These depolarizations are very rapid and are specific to receptor sites found on A-delta nerve fibers, which propagate at 5 to 25 m / sec toward the spinal cord.

[0037] Otherwise, the nerve impulse can propagate through unmyelinated axons found in type A delta diffuse pain nerve fibers, as shown in Figures 6 and 7, and type C diffuse pain nerve fibers, as shown in Figures 8 and 9. Here, stimulation causes the nerve impulse to propagate in both directions, but continues to propagate more easily and quickly toward the spinal cord. The propagation of the impulse in C fibers 60 is much slower than in A delta fibers, only 0.1 to 2.0 m / sec in those C fibers 60 that conduct pain impulses.

[0038] Local anesthesia provides analgesia and pain relief by blocking the nerve's electrical sodium / potassium action potential as the nerve impulse continues to travel, either at the nodes of Ranvier in A-delta sharp pain fibers (Figures 6 and 7) or along unmyelinated C diffuse pain fibers (Figures 8 and 9). Blocking this action potential at three successive nodes of Ranvier in A-delta fibers, or at the equivalent axonal surface in C fibers, is sufficient to block the nerve impulse from traveling down the nerve axon to the spinal cord. In this way, local anesthesia can block both sensory and motor impulses in both A-delta and C fibers, as a central (spinal or epidural) or peripheral nerve block.

[0039] The degree of motor versus sensory block varies considerably with different local anesthetics. Some local anesthetic drugs exhibit equal efficacy for motor and sensory block (e.g., etidocaine), while others exhibit a much greater propensity for sensory block than motor block (e.g., bupivacaine). In terms of long-lasting local anesthetic blocks for postoperative prophylaxis, the amide-type long-acting local anesthetics (bupivacaine, ropivacaine, and derivatives) are far superior in maximizing the duration of pain relief while minimizing motor block. Such long-acting nerve blocks, if they can be made to last long enough, would greatly reduce or completely eliminate the need for postoperative opioid analgesics. To this end, bupivacaine and ropivacaine have proven to be the most effective currently available.

[0040] Previous IP explorations have gone beyond traditional local anesthetic nerve block injections, proposing sensory nerve blocks that extend analgesia for up to 72 hours by injecting physiological bases during or after surgery. This prior IP, while very broad in its claims, lacks precision and understanding of the intraneuronal mechanisms that extend analgesia to 120 hours or more. Specifically, Abramsohn claims that sodium bicarbonate (NaHCO 3 ) is used for local anesthesia, a step essential to this invention. 3 ) or sodium carbonate (Na 2 CO 3 ) is denied to occur simultaneously.

[0041] As shown in FIG. 10-24, the present invention includes a long-acting local anesthetic 99 that requires a combination of a short-acting amide-type local anesthetic 76 and a physiological base 78. This allows NaHCO 3 to be delivered together with the first local anesthetic through the axolemma into the axon body. 3 / Na 2 CO 3 82) into the axon itself, which then binds subsequent long-acting local anesthetics of the amide type (ALALA-bupivacaine, levobupivacaine, ropivacaine) and causes precipitation and crystallization of the ALA-carbonate compound 82 within and outside the axon. 3 / Na 2 CO 3 It is this ALALA-carbonate precipitation and crystallization that produces an analgesia lasting 120 hours or more.82 Abram Thorne has 3 This invention involving in vivo ALALA-carbonate precipitation and crystallization is in direct opposition to the Abramsohn intellectual property, as it expressly prohibits direct mixing of ALALA with ALALA. It is solely by forming this precipitation and crystallization in or on the target that the 120 hour block is achievable. ALALA - Formation mechanism of carbonate precipitates and crystals

[0042] As shown in Figures 10 and 11, the first stage of this new long-acting local anesthetic is a short-acting ALA drug that does not precipitate in alkaline solutions with a pH of 10 or less, e.g., sodium bicarbonate (NaHCO 3 ) / Sodium Carbonate (Na 2 CO 3 The injection of lidocaine 76 with an alkaline NaHCO 3 (NaOH) / sodium hydroxide mixture, which is the opposite of the use of a local anesthetic and a sodium carbonate / bicarbonate base in the prior art (Abramsohn). 3 / Na 2 CO 3 Adding the NaHCO3 / NaOH mixture raises the pH of lidocaine and shifts its protonated (+) 72:unprotonated (-) balance to mostly (~95%) unprotonated (-) molecules 70. This unprotonated form of lidocaine 76 penetrates the nerve membrane (axolemma) more easily into the axon. However, because it is uncharged, it does not cause nerve impulse inhibition (pain relief and numbness). Its small size makes it more suitable for use as a protonated (+) 72:unprotonated (-) molecule. 3 and Na 2 CO 3 The protonated lidocaine (+) 72 rapidly travels together with the non-protonated lidocaine (-) 70 into the axon 24, creating a temporary alkaline intra-axonal environment. Some of the non-ionized lidocaine (-) inside the nerve cell then begins to equilibrate, producing the neurologically active ionized lidocaine (+). It causes the nerve impulse to be blocked through the nerve cell. This protonated lidocaine (+) 72 interferes with the nerve's sodium-potassium pump, making it inactive. This causes the transmission of the nerve impulse to the nerve to be blocked, forming a nerve block (paralysis or insensibility). In this way, when the three nodes of Ranvier are blocked, the nerve impulse cannot travel along the axon, and the nerve is actively blocked (blocked) by the local anesthetic.

[0043] As shown in Figures 12 and 13, NaHCO 3 / Na 2 CO 3Once the ALALA is substantially inside the axon 24 (which occurs within a small fraction of time of injection into the nerve), a second injection is made with a long-acting local anesthetic of the amide type, such as bupivacaine (shown in Figures 12 and 13 as an example of an ALALA compound). Due to their elevated acid dissociation constants, pKa, ALALA drugs form crystallized precipitates 82 both intra- and extra-axonally (at the nodes of Ranvier 20 of Aδ fibers, and mostly around the axon of C fibers) in an alkaline environment. 3 When mixed in equal proportions, a 0.75% bupivacaine solution (225 mg of bupivacaine) will precipitate 92.53% bupivacaine by weight (with only 7.47% remaining in solution). 3 and 0.75% ropivacaine, precipitated ropivacaine occurs as 96.50% drug by weight with only 3.50% remaining in solution. Levobupivacaine is similarly expected to precipitate and crystallize with 96.5% conversion once the drug is available.

[0044] As shown in Figure 12-16, crystalline ALALA-carbonate precipitates 82 (bupivacaine carbonate shown in Figure 12-16) collect and crystallize in and around nerve axons 24 in both Aδ and C fibers 90. Simultaneously, these alkaline ALALA-precipitates (at pH>7) condense into larger crystals, forming an inactive storehouse of local anesthetic 90. It slowly dissolves into the non-ionized form (ALALA-)+H before re-equilibrating to the ionized form (ALALA+) that continues nerve blockade and resulting pain relief for multiple days. 2 O&CO 2 96. Thus, it is the alkaline pH of the ALALA-carbonate precipitate crystals that is responsible for extending the duration of the nerve block.

[0045] Crystalline bupivacaine carbonate is generated in vivo and collects as precipitate deposits inside and outside the axon (at the nodes of Ranvier for Aδ fibers and throughout the axon for C fibers). Although much of the extra-axonal bupivacaine carbonate is eventually swept away by circulating lymph, a significant proportion remains and acts as bupivacaine deposits that contribute to the extended duration of nerve block. Much of the extended duration of nerve block is due to the amount of bupivacaine carbonate precipitate that is generated inside the axons of both Aδ and C fibers.

[0046] The ALALA-carbonate precipitates inside the body do not remain stable, but rather decompose to the unprotonated (-) form. Furthermore, carbon dioxide (CO 2 ), water (H 2 O) and salt (NaCl) return the axon to its normal pH of 7.4 in the alkaline environment inside the axon. 2 O and NaCl are reabsorbed into the lymph and blood. 2 O and NaCl are absorbed through the kidneys, and CO 2 is eventually removed through the lungs. The initial breakdown of bupivacaine carbonate produces unprotonated (-) bupivacaine in an alkaline environment, but the production of protonated (+) bupivacaine is limited, but sufficient to extend the duration of the already existing nerve blockade. As the pH value of much of the alkaline environment in the axon returns to pH 7.4, more bupivacaine carbonate gains protons and becomes active, blocking the neuronal sodium-potassium pump and enhancing the nerve blockade. Eventually, all bupivacaine carbonate breaks down to bupivacaine (-) and protonated bupivacaine (+), blocking the nerve receptors and being metabolized. Only when the last bupivacaine (+) is metabolized does the nerve blockade gradually disappear in individual Aδ and C fibers.

[0047] Because nerve metabolism in A-delta fibers is more rapid than in C-fibers, A-delta pain fibers regain normal sensation more quickly than their C-fiber counterparts. This typically results in an A-delta nerve block of 48-72 hours duration. However, preferred C-fiber blocks can last 120 hours or more. A 120-hour sensory (sensory) nerve block can relieve the need for opioid analgesics after surgery. It is the elimination of the need for opioids after surgery that closes the gateway that now exists and through which many people enter opioid addiction. Adjuvants

[0048] The ALALA-carbonate block can be augmented by the addition of other peripheral nerve block adjuvants, including alpha-adrenergic markers and vasoconstrictor agents such as epinephrine (adrenaline), clonidine, and dexmedetomidine. 2 -agonists, dexamethasone, betamethasone, triamcinolone, and other steroids. Steroid 88 can be used alone to crystallize amide-type local anesthetics and form NaHCO 3 / Na 2 CO 3 / NaOH, and other physiological bases by another mechanism.

[0049] Physiological base 76 (NaHCO 3 / Na 2 CO 3It has been recently realized that steroids (NaHCO3 / NaOH) are not the only class of compounds capable of precipitating local anesthetics, especially the ALALA compound. Steroids 88 also have the ability to precipitate the ALALA compound. It is not yet clear whether this is due to intraneural or extraneural deposition of the ALA local anesthetic. However, it is already known in the literature that in ALALA peripheral nerve blocks, steroid supplementation with ropivacaine and bupivacaine allows the block to last for 16 to 24 hours, and sometimes up to 30 hours. In the present invention, the inclusion of steroids in the ALALA compound block does indeed result in prolonged analgesia, either due to intraneural (axonal) or extraneural deposition of the ALALA-carbonate compound. However, NaHCO3 3 Removing it always results in a block of ~30 hours or less.

[0050] Na 2 CO 3 , NaHCO 3 By combining various amounts of steroids (currently dexamethasone and betamethasone) in various doses, the duration of analgesia can be adjusted to suit the length of analgesia required after surgery. This is relevant to this invention. 3 (pH=8-9) and Na 2 CO 3 It is believed that various combinations of NaHCO (pH=10-11) can produce the desired alkaline environment and control not only the pH of the environment but also the absorption of carbonate base into the axon of the neuron. pH is the control that determines the amount of precipitation and the crystal size in the formation of ALALA-carbonate, and is further modified by corticosteroids. As we have found, higher concentrations of NaHCO 3 / Na 2 CO 3and / or steroids can result in a significantly longer period of analgesia, in excess of 120 hours. Thus, a predictable and titratable period of analgesia (pain relief) is a function of the amount of drug and the concentration of the compositional components in the ALALA-carbonate nerve block. Thus, nerve blocks can be scheduled to last for a specific period of time as a function of the amount / concentration of each component in the ALALA-compound block. ALALA - Compound Nerve Block Creation Protocol

[0051] As shown in Figure 17-23, the establishment of a 5-day peripheral nerve block involves the injection of two separate, sequential solutions that will produce a precipitate and crystallize the ALALA-Compound in vivo around the nerve targeted for the specific nerve block. The two solutions must be kept separate until injection onto the specific nerve is accomplished, after which the solutions will react and produce a precipitate and crystallize the ALALA-Compound in vivo.

[0052] This separation of the solutions is by two different means: 1. Sequential injection of two separate solutions through a single needle (Figs. 17-19 and 22). 2. Injecting both solutions simultaneously through a bifurcated needle so that mixing occurs only at the needle tip facing the target nerve (Figures 20 and 21).

[0053] These alkaline solutions are: 1. Solution 1-4% lidocaine + 1:200,000 epinephrine (adrenaline) + 8.4%-10% NaHCO 3 4% lidocaine and 8.4% NaHCO 3 / Na 2 CO 3Epinephrine (adrenaline) 86 is ~3 mcg / ml and is present initially as a standard vascular marker that, if leaked into the vascular system, will result in mild tachycardia. Once Solution 1 is given, a pulse oximeter or EKG rhythm strip should be performed to ensure there is no tachycardia for 2 minutes to ensure that Solution 1 is not leaking into the vascular system resulting in a tachycardia greater than 15% of the baseline pulse rate.

[0054] As long-acting local anesthetics of the amide type have the potential for cardiotoxicity and can cause seizures and even cardiac arrest, such provision requires legal mandate to avoid inadvertent injection of solution 1 into the vascular system. This precaution is important for the safety of patients with ALALA-compound blockade.

[0055] Regarding epinephrine (adrenaline) as described in steps 1 and 2, since the 1980s there has been a precise protocol that is currently followed in all hospitals (test dose) to avoid cardiotoxic reactions to ALALA agents in epidural catheters after placement and upon application.

[0056] 2. If during the slow injection of solution 1 a tachycardia of 15% or more of the baseline pulse occurs, the block is immediately discontinued, as the epinephrine (adrenaline) tachycardia is taken as evidence of intravascular leakage of solution 1. In such a situation, if solution 2 is subsequently injected, the patient will suffer seizures and cardiac arrest due to local anesthetic toxicity. For this reason, the standard protocol of a 2-minute wait is given between epinephrine (adrenaline)-containing solution 1 and solution 2. Solution 2 is injected only when it has been determined that there has been no significant increase in pulse rate of more than 15% of the baseline pulse during the 2 minutes.

[0057] 3. The injection of clearing solution 84 through the needle is intended to prevent mixing of solutions 1 and 2, thereby creating precipitates / crystals that may clog the lumen of the needle before solution 2 has been fully injected. This prevents complete mixing of solutions 1 and 2, and therefore incomplete production of precipitates / crystals. To prevent this, solution 1 must be cleaned from the single lumen needle before injecting solution 2.

[0058] 4. Solution 2 - 0.75% bupivacaine, 0.75% levobupivacaine, or 1% ropivacaine as the sole component for solution 2, usually in an amount equal to that of solution 1.

[0059] Higher concentrations of the ALALA compound component may result in a more prolonged block of pain relief, with larger and more abundant crystals being produced. 3 is already a saturated solution, so there is no NaHCO 3 However, it is not possible to increase the amount of NaHCO 3 :Na 2 CO 3 Na in the mixture 2 CO 3 Increasing the concentration of can be done, thereby raising the pH, making the final mixture higher in pH and resulting in more precipitation and crystallization.

[0060] Physiological 8.4% NaHCO 3 (at pH ~8) added to an equal volume of 4% lidocaine in solution 1, NaHCO 3 The final concentrations of NaHCO and lidocaine are shifted to 4.2% and 2%, respectively, and the pH is lowered. If an equal volume of solution 2 is added to this mixture, it is further diluted, becoming only 2.1% NaHCO 3 This dilution produces a precipitate around the nerve with associated pH. This dilution lowers the acid-base balance of the final solution to a point just above pH 7.4 (physiologic).

[0061] Solution 1: NaHCO 3The pH of Na 2 CO 3 If the pH of the final perineural solution is raised to the point of ~pH=8 by adding 100% ethanol, a much greater concentration of ALALA-carbonate precipitate can be produced, resulting in a much longer duration of pain relief from the nerve block. This will prove very useful for longer and more complex surgeries, and even chronic pain syndromes.

[0062] The physiological base pH of solution 1 increases, prolonging analgesia as well as increasing the axonal content of these drugs in the precipitate / crystallize, thus increasing the ALALA drugs, steroids, alpha-antibody drugs such as clonidine and dexmedetomidine. 2 The same can be achieved by increasing the dose of NMDA agonist with agonist, NSAID, or other adjuvants. These can functionally extend pain relief to 14 days or more, help suppress the neurofeedback that causes Chronic Regional Pain Syndromes (CRPS), and restore normalcy to the spinal cord. Further animal studies will demonstrate which drug and at what concentration is more useful than our current mixture of solutions 1 and 2.

[0063] When these solutions are injected sequentially through a single needle (Figures 17 and 22), the material in solution 1 must be removed before injecting solution 2. 3 Solution 1 can cause the bupivacaine or ropivacaine in solution 2 to precipitate in the needle, clogging it. Therefore, solution 1 must be flushed from the lumen of a single needle before injecting solution 2 through that needle. This problem is prevented by the delivery device or dispenser of the present invention, a bonded or internally bifurcated needle. This allows for the subsequent injection of these solutions while always eliminating the possibility of needle clogging due to precipitation (Figures 18-21).

[0064] Solution 1 was injected around the peripheral nerve and immediately NaHCO 3 and Na2 CO 3 pushes the protonated / unbound biochemical balance of lidocaine toward the nearly 95% unbound point, since the unbound portion of the local anesthetic is important for axonal tissue penetration. Lidocaine is then taken up into the axon in larger amounts than normal, and together with this large amount of lidocaine, NaHCO 3 is also taken up into the axon.

[0065] NaHCO in solution 1 3 When mixed with bupivacaine, levobupivacaine, or ropivacaine in solution 2, 8.4% NaHCO immediately precipitates these drugs into crystals in this alkaline solution. 3 When mixed in equal proportions with 8.4% NaHCO, a 0.75% bupivacaine solution (225 mg) will cause 93.53% of the drug mass to precipitate (with only 7.47% remaining in the solution). 3 and 0.75% ropivacaine, 96.50% of the drug dose precipitated, leaving only 3.50% ropivacaine remaining in solution.

[0066] Without moving the ultrasound-placed single-lumen needle from its location to the next nerve, the needle was filled with NaHCO before being injected with an equal volume of solution 2 as solution 1 in a subsequent injection. 3 (with saline or air). With the bonded or internally bifurcated needles of the present invention, this removal step is not necessary.

[0067] Bupivacaine (or ropivacaine) is a sodium bicarbonate (NaHCO 3As it flows into the lidocaine solution 1, the bupivacaine begins to precipitate. The predominant agent will precipitate outside the axon sheath and will therefore be removed over time by the normal lymphatic flow around the nerve. Steroids have been shown to precipitate local anesthetics in vitro and are expected to perform the same function in vivo. Recent literature has interpreted this reaction as a precaution against combining steroids with bupivacaine in epidural anesthesia. However, what is wrong with epidural blocks, when a peripheral nerve anesthetic is used instead of an opioid, can a longer block be performed? Betamethasone and dexamethasone create more precipitate with bupivacaine and ropivacaine, resulting in the NaHCO in solution 1. 3 When combined with anesthetic, a longer, long-acting local anesthetic block can be obtained.

[0068] NaHCO for solution 1 3 and NaHCO depending on steroid concentration / drug dose. 3 / Na 2 CO 3 and other steroids, different dosages will produce different lengths of effective analgesia. In theory, for other steroids not listed here, greater intraaxonal or nodal deposition of amide-type long-lasting local anesthetics will be evident over time, along with a proportionately greater time to postoperative analgesia.

[0069] Only a small amount of bupivacaine (approximately 11.9%) penetrates the axonal sheath or ganglion before precipitating as bupivacaine carbonate. It is this small amount of bupivacaine inside the axonal sheath / ganglion that initially provides the nerve blockade for up to 120 hours or more.

[0070] However, due to the altered final pH from the combination of the ALALA agent and all of the adjuvants and base / precipitants, these solutions will force more ALALA precipitate / crystals for a longer and denser nerve block, which is the goal of the alternative protocol for creating an ALALA-precipitate nerve block. Alternative Protocol for the Creation of ALALA-Precipitate Nerve Blocks

[0071] As shown in FIG. 24, there is an alternative protocol, which shows advantages over the initial protocol when placing a nerve block desired to last longer than 120 hours.

[0072] In this alternative protocol, all that is required first is to prove that placement of the block needle has not opened vascular connections by a "test dose" with or without adjuvant, as shown in stage 1 of Figure 24. However, tachycardia does not develop as a result of this test dose. > If vascular access was evident by 115% of baseline, local anesthetic (lidocaine) with epinephrine plus included adjuvants would be the nerve block the patient would receive at that location and time. No ALALA agents should be given, nor should physiological base be given. Thus, intravascular injection of ALALA agents, with associated risks of seizures, cardiac arrhythmias, and cardiac arrest, should be avoided.

[0073] There is still a mandatory 2 minute wait (shown in stage 2) as the test dose reveals whether there is a connection to the body's vascular system. Again, this way, ALALA drugs that cause cardiotoxic reactions including seizures, arrhythmias and cardiac arrest are avoided by using the test dose. This has been done with obstetric epidural anesthesia catheters since the 1980s to prevent ALALA cardiotoxic reactions.

[0074] Immediately following stage 2 is stage 3 which involves the injection of the ALALA agent in the amount of agent required to produce the desired duration of analgesia from this nerve block. This stage contains an adjuvant but no precipitating steroid and no physiological base, which will cause the ALALA agent to precipitate when bound to the body and outside the target nerve.

[0075] In stage 4, where the ALALA agent has already precipitated or precipitated around the nerve, the single lumen needle is flushed with a clearing solution such as saline. This prepares the block needle for stage 5 and the physiological base and / or precipitated steroid.

[0076] In stage 5, the calculated base and steroid are injected to raise the pH of all of the injected drugs in stages 1-4 to pH ~8.0 (7.4 to 8.4), thereby producing the correct amount of precipitate and crystals (physiologic base and steroid) for the desired duration of the peripheral nerve block, from 3 to 30 days or more.

[0077] This alternative method brings the pH to the final in vivo pH so that the volume of injectate is no longer equivalent. By using a lower dose of base / steroid with a higher pH, the desired final pH of the ALALA drug and adjuvant can be produced to produce the desired precipitation for the desired duration of analgesia.

[0078] In this alternative method, the amount of precipitate (physiological base and steroid) can be controlled by optimizing the pH during the nerve block, thereby controlling the desired block density and duration. A simple table can be written down for each drug type and name, as well as the density obtained, to provide a specific duration and length of nerve block as desired. This is particularly necessary when treating patients with chronic pain, especially those with chronic regional pain syndrome.

[0079] Numerous scientific publications advise against adding excess carbonate base and steroids (especially corticosteroids) as they cause precipitation of ALALA agents (bupivacaine, levobupivacaine, ropivacaine). Tetracaine, an ester-type long-acting local anesthetic (ELALA), which has a higher pKA than bupivacaine, will also precipitate in carbonate base and steroids.

[0080] Although the scientific literature recommends restriction to avoid the formation of local anesthetic precipitates, our intellectual property is intended to create these precipitates within nerve cells and axons as depots of ALALA or ELALA agents that will allow nerve blockade to continue for well beyond three days. The amount of agent and composition of these precipitates will determine the duration of the nerve block so created, and therefore the duration of pain relief.

[0081] The production of ALALA precipitates inside the nerves is the basis for a longer-term interruption of the sodium-potassium ion pump inside the nerve cells. When this pump does not function, so too does the neurotransmission of pain impulses, thereby providing analgesia in post-operative and trauma patients when nerve blocks are given.

[0082] There are a variety of carbonate and steroid agents that can be combined with ALALA (and ELALA) agents to produce local anesthetic deposits that vary in duration from 3 to 30 days or more.

[0083] Physiological carbonate base is originally sodium bicarbonate (NaHCO 3 ), Sodium Carbonate (Na 2 CO 3 ), and sodium hydroxide (NaOH). Each of these solutions has a different saturated pH, so various combinations of these solutions can be used to create a final common solution of the desired pH. This is important in obtaining the desired ALALA or ELALA precipitate within the nerve when a specific duration of analgesia is desired from a peripheral nerve block.

[0084] As we found in our laboratory, 8.4% NaHCO 3 When combined in vitro with bupivacaine or ropivacaine, it results in the precipitation of 93.5% and 96.5%, respectively, of the parent ALALA drug. However, NaHCO 3When diluted with lidocaine and adjuvant and then diluted again with an equal volume of ALALA drug, 3 The percentage of ALALA is diluted from 8.4% to 2.1%, with a concomitant decrease in pH and much less conversion of the ALALA agent to precipitate. By controlling the pH of the final combination of all of these agents and base, the percentage of ALALA that precipitates and crystallizes, and thereby the duration of the resulting nerve block, can be more effectively controlled.

[0085] Similarly, the combination of ALALA (or ELALA) local anesthetic agents with steroids, particularly corticosteroids, also causes ALALA precipitates. Some of these precipitates migrate into the axons of the nerves, producing intraneuronal ALALA or ELALA steroid deposits. Corticosteroids that are effective in producing these deposits include dexamethasone, betamethasone, and triamcinolone. Such combinations of steroids with ALALA or ELALA agents can result in clinically useful deposits, as generally shown in the table below: Table 1: Possible local anesthetics and precipitating bases and steroids

[0086] [Table 1] Table 2: Possible local anesthetics and precipitating bases and steroids

[0087] [Table 2]

[0088] As shown in Table 2 above, once levobupivacaine and ropivacaine are considered, the total possible variations is 3x10 28 For some of these chemical interactions, PABA can be removed from the tetracycline specification. In this case, the total possible useful variation from this matrix is ​​4x10 28 It is. Table 3: ALALA precipitate blocks identified to date

[0089] [Table 3]

[0090] Table 3 above shows the currently identified ingredients of ALALA Precipitate Block: 1.ALALA drugs- Bupivacaine, Levobupivacaine, Ropivacaine. 2. Physiological base – NaHCO at pH ~8.0-8.2 3 -Na, a common primary physiological base and a standard solution with a pH of ~8-9 2 CO 3 , but the crystals added directly to the mixture have a pH of 11.5.

[0091] The promise of this invention is to add both of these bases together to the solution to control the pH and thereby precipitate the ALALA compound in the range of the final mixture between pH 7.5 and pH 8.4. The appropriate alkaline pH is needed to control the degree or amount of ALALA precipitation which controls the duration of these ALA precipitate nerve blocks. If a small total volume is required for the final injectate volume, NaHCO 3 / Na 2 CO 3 By adding a few more crystals of NaOH to the solutions, the desired pH can be achieved prior to nerve block injection. 2 CO 3 As NaHCO 3 The increased concentration of α-glucose phosphate ...

[0092] Precipitated steroids, primarily dexamethasone and betamethasone corticosteroids. These two corticosteroids are currently used in formal peripheral nerve blocks to extend the ALALA block wear-off from 12-16 hours to a useful range of 24 hours. Given Fan's cautionary paper, the presumed cause is that the ALALA precipitate fills the gap time between when the initial lidocaine + epinephrine wears off and when the ALALA carbonate returns to the beginning of the protonated ALALA that continues the nerve block lidocaine. Effective doses for these corticosteroids are listed above. It may be necessary to use one or both corticosteroids simultaneously, resulting in both 10x and 20x changes in steroid use.

[0093] 4. Adjuvants- These are mainly α 2 Agonist drugs – dexmedetomidine and clonidine – act against alpha receptors in the spinal cord. 2These are agents known to block pain receptors and are also believed to act on peripheral nerves. Indeed, dexmedetomidine and clonidine, together with corticosteroids, are understood to extend standard peripheral nerve blocks with bupivacaine and ropivacaine ~50%. These 2 Increasing doses of agonists result in increased duration of these nerve blocks. These agents are used in 100x variations of each.

[0094] Therefore, the possible variations for these bupivacaine blocks are 25x10x20x100x100=5,000,000 variations for drugs with bupivacaine. Similarly, for bupivacaine and ropivacaine, a total of 15,000,000 variations are available compounds with these ALALA drugs.

[0095] Although it precipitates in tetracaine, physiological bases, and corticosteroids, it is believed that toxic PABA is not released upon decomposition of these large peripheral nerve block drug doses. This is too dangerous for use in humans, until safer variations of the ELALA drugs, or a means of detoxifying them, can be found.

[0096] While other variations show some promise, these are the ones most likely to produce the 120 hour or greater long lasting block sought by this invention.

[0097] Both ALALA carbonate and steroid precipitates can form intraneuronal precipitate stores which upon decomposition produce salt, water, carbon dioxide and unprotonated ALALA drug. The unprotonated ALALA form gains a proton and equilibrates with its protonated (+) neutral active form. It is this neutral active protonated form that blocks the sodium-potassium ion pumps in neurons and axons, thereby interrupting pain neurotransmission, resulting in analgesia and pain relief.

[0098] The possible combinations of these drugs and bases total 3x10 28 The first matrix is ​​then multiplied by the number of different adjuvants. The different adjuvants include all the α 2 Adjuvants, NSAIDs, NMDA antagonists, and their blockers 2 These variations are multiplied by the different ratios of each carbonate base and the drug doses of each different steroid, which affect the strength and longevity of the final nerve block. This results in a matrix with thousands, or even tens of thousands, of entries and variations that control the strength and longevity of the nerve block.

[0099] Nerve block concentration and longevity are controlled by titration of carbonate or steroid to achieve a specific target pH in the desired final ALALA compound, so that various dilutions of carbonate base and steroid can provide the desired final pH and precipitation as needed for the intended nerve block concentration and longevity.

[0100] Considering the above, some of these combinations may not provide satisfactory analgesia and others may not be practical for use in living tissue. However, the majority are quite effective in providing ALALA (or ELALA) precipitates that result in a variety of nerve blocks with analgesia for 3 to 30 days or more. Other compounds may be found to extend these same intraneural ALALA (or ELALA) precipitates in the future, thus providing more efficient and titratable nerve blocks and analgesia. These combinations could be used with peripheral nerve blocks or perianesthetics to provide post-operative and post-traumatic analgesia for the specific block concentration and duration desired. Ester-type local anesthetic

[0101] This means that tetracaine, an ester-type local anesthetic, has a higher pKa than bupivacaine and is more effective at reducing NaHCO 3 and Na 2 CO 3 It precipitates in the presence of bupivacaine and also produces a similarly long-lasting local anesthetic block. However, as an ester-type local anesthetic, tetracaine degrades to para-aminobenzoic acid (PABA), a known allergen that causes severe and violent allergic reactions. Considering that these anaphylactic reactions are known at doses of 10 mg and less, the 100 mg to 200 mg or higher doses required for peripheral nerve blocks would greatly increase the frequency of occurrence. A dose of 200 mg would be fatal to any human. For this reason, tetracaine will not be utilized in dose-dependent peripheral nerve blocks, as is currently the case, until clinical testing can produce an ester or other that provides longer-lasting local anesthetic action than that of bupivacaine without significant toxicity. However, when a non-allergenic version of this block without the prohibited toxicity becomes possible, this intellectual property will be exploited with the necessary tetracaine content. Competing Intellectual Property

[0102] Exparel is a liposome-encapsulated bupivacaine that was first released in 2012. Its unique formulation advertises nerve block analgesia lasting up to three days and has been described as an improvement in non-opioid pain relief following surgery. However, performance in this role has proven inferior to that claim, with most blocks lasting only 36 to 48 hours.

[0103] Exparel utilizes a surrounding liposomal shell of different thicknesses as a time-release mechanism to gradually release the encased bupivacaine upon injection of a peripheral nerve block. The liposomal shell degrades over time before releasing the encapsulated bupivacaine. Different shell thicknesses allow for different releases of the local anesthetic. This allows for a sustained release of bupivacaine, extending postoperative analgesia for peripheral nerve blocks to the advertised 72 hours. While Exparel is somewhat effective in analgesia for periods less than 48 hours, this mechanism has severe limitations in extending the block to 72 hours, as it results in significant vulnerability in the release of the bupivacaine when challenged with certain conditions, sometimes unexpectedly. Thus, complete prevention of local anesthetic toxicity (LAST) cannot be achieved with a full vial of 250 mg bupivacaine with Exparel.

[0104] Despite its shortcomings, Exparel has made great strides in increasing postoperative analgesia, but it still proves inadequate in providing the 120 hours of postoperative analgesia required to minimize or eliminate the need for opioid analgesics.

[0105] Abrahamson's IP suffers from a number of inadequacies. Abrahamson specifies a temporal and spatial separation of the injection of the anion (HCO3) from any local anesthetic injection. This is due to the use of NaHCO3 to create the ALALA carbonate precipitate. 3This has the effect of decreasing the reaction between the ALALA drug and the precipitation. Since this precipitation is the mechanism by which post-operative pain relief is prolonged, the Abrahamson technique is insufficient to provide optimal and reliable pain relief after surgical procedures, and does not achieve an extended period of pain relief beyond 72 hours. As such, the Abrahamson interval times are not consistent and vary significantly from the listed 0.5 to 72 hours.

[0106] The method of the invention requires, in most cases, precise ultrasound-guided positioning of the block needle toward, but not penetrating, the target nerve prior to delivery of the ALALA carbonate / steroid nerve block in vivo. This allows the solution to be delivered closest to the target nerve, which creates ALALA carbonate and ALALA steroid precipitates in and around the target nerve, resulting in 12 hours of pain relief for surgical patients. Reliably and reproducibly provides post-operative analgesia greater than 0 hours.

[0107] Anesthetic nerve block 98 blocks electrical potential of nerve 12 and relieves pain inside organism 10. As shown in FIG. 1-16, nerve 12 includes epineurium 14, perineurium 16, endoneurium 18, nodes of Ranvier 20, myelin sheath 22, axon 24, neuronal cell body 30, raphe nuclei 32, dendrites 34, axon terminal 36, oligodendrocytes (Schwann cells) 38, myelin envelope 40, microtubules 42, microfilaments 44, myelinated neurons (Aδ fibers) 50, peripheral terminals 52, nerve membrane (axolemma) 54, and unmyelinated neurons (C fibers) 60.

[0108] The axon 24 is covered by the nerve membrane (axolemma) 54. The anesthetic nerve block 98 includes a dispenser 102 including a storage body 104, a transfer body 106, and a tip 108 for positioning adjacent to the nerve 12. A short-acting local anesthetic 76 is within the storage body 104. A physiological carbonate base 78 is within the storage body 104. The short-acting local anesthetic 76 and the physiological carbonate base 78 are dispensed from the tip 108 of the dispenser 102, where the short-acting local anesthetic 76 aids in the penetration of the physiological carbonate base 78 through the nerve membrane (axolemma) 54 into the axon 24. A long-acting local anesthetic 80 is within the storage body 104. The long-acting local anesthetic 80 is dispensed from the tip 108 of the dispenser 102 and penetrates through the nerve membrane (axolemma) 54 into the axon 24. The long-acting local anesthetic 80 and physiological carbonate base 78 precipitate to produce a crystallized compound that creates a prolonged local nerve block 99.

[0109] 17, the dispenser 102 can include a continuous injection system 100 of an anesthetic agent. The continuous injection system 100 of an anesthetic agent includes a syringe 110 having a barrel 112 that slidably receives a plunger 114 and dispenses through a needle 116. The dispenser 102 can include a number of barrel membranes 118 that can maintain separation of the short acting local anesthetic agent 76, the physiological carbonate base 78, and the long acting local anesthetic agent 80 within the barrel 112.

[0110] Saline 84 may be positioned within the barrel 112. A plurality of barrel membranes 118 hold the saline 84 between the physiological carbonate base 78 and the long acting local anesthetic 80 within the barrel 112. The saline 84 washes the needle 116 after dispensing the short acting local anesthetic 76 and the physiological carbonate base 78 from the needle 116. An impalement needle 120 may be positioned within the barrel 112 such that, upon depression of the plunger 114, the plurality of barrel membranes 118 may be sequentially ruptured and solution may be allowed to exit the barrel 112.

[0111] As shown in Figures 18 and 19, an alternative to the dispenser 102 may include a first dispenser 134 and a second dispenser 142. The first dispenser 134 has a first storage body 136, a first transfer body 138, and a first tip 140 for dispensing the short acting local anesthetic 76 and the physiological carbonate base 78. The second dispenser 142 has a second storage body 144, a second transfer body 146, and a second tip 148 for dispensing the long acting local anesthetic or the local long acting anesthetic 80. The dispenser 102 may include a coaxial needle or multiple needles 130 linked together for parallel injections. The multiple needles 130 linked together have a common outlet 132 at the tip and mixing of the separate lumens occurs at the tip 108 of the needle 116.

[0112] As shown in Figures 20 and 21, the dispenser 102 can include a transfer body 106 with a bisecting transfer wall 150. The bisecting transfer wall 150 separates and separates a first transfer body 152 and a second transfer body 154. The first transfer body 152 dispenses a short acting local anesthetic 76 and a physiological carbonate base 78. The second transfer body 154 dispenses a long acting local anesthetic 80. The bisecting transfer wall 150 prevents the fluids from mixing except at the tip 108.

[0113] As shown in FIG. 22, the dispenser 102 can include a first syringe 160, a second syringe 170, and a third syringe 180. The first syringe 160 has a first barrel 162 that slidably receives a first plunger 164. The first barrel 162 contains a short-acting local anesthetic 76 and a physiological carbonate base 78. The second syringe 170 has a second barrel 172 that slidably receives a second plunger 174. The second barrel 172 contains a saline solution 84. The third syringe 180 has a third barrel 182 that slidably receives a third plunger 184. The third barrel 182 contains a long-acting local anesthetic 80. A stopcock 186 connects the first barrel 162, the second barrel 172, and the third barrel 182 with the needle 116. The stopcock 186 is positioned to sequentially dispense the short acting local anesthetic 76 and physiological carbonate base 78, the saline 84, and the long acting local anesthetic 80. The saline 84 rinses the needle 116 after the short acting local anesthetic 76 and physiological carbonate base 78 have been dispensed from the needle 116. A tubing 192 may be positioned between the stopcock 186 and the needle 116. A side cylinder 190 may be coupled to the first syringe 160, the second syringe 170, and / or the third syringe 180. The side cylinder 190 is for dispensing adjuvants, such as additional physiological carbonate base 78, steroids 88, epinephrine 86, and the long acting local anesthetic 80.

[0114] Combining the short-acting local anesthetic 76 with the physiological carbonate base 78 results in an increase in the pH of the short-acting local anesthetic 76 and converts the short-acting local anesthetic 76 into an unprotonated (-) molecule, making the short-acting local anesthetic 76 and the physiological carbonate base 78 more easily locate through the nerve membrane 54 and into the axon 24. The pH level of the physiological carbonate base 78 determines the amount of precipitation and the size of the crystals in the crystallizing compound 82. By increasing the amount / concentration level of the physiological carbonate base 78, the pH of the final mixture can be made higher, resulting in a longer duration of nerve block. Alternatively, by decreasing the amount / concentration level of the physiological carbonate base 78, the pH of the final mixture can be made lower, resulting in a shorter duration of nerve block. Adjusting the amount / concentration level of the physiological carbonate base 78 determines different nerve block durations. Furthermore, adjusting the amount / concentration level of the physiological carbonate base 78 determines different nerve block concentrations.

[0115] The short acting local anesthetics 76 can include lidocaine. The long acting local anesthetics 80 can include bupivacaine, levobupivacaine, ropivacaine and tetracaine. The physiological carbonate bases 78 can include sodium bicarbonate, sodium carbonate and sodium hydroxide.

[0116] The anesthetic nerve block 98 may further include or alternately include a steroid 88 in the storage body 104. The steroid 88 may include dexamethasone, betamethasone, and triamcinolone, as well as other adjuvants. The short-acting local anesthetic 76 and the steroid 88 are dispensed from the tip 108 of the dispenser 102, where the short-acting local anesthetic 76 aids the steroid 88 in penetrating through the axolemma 54 into the axon 24. The long-acting local anesthetic 80 is in the storage body 104. The long-acting local anesthetic 80 is dispensed from the tip 108 of the dispenser 102, where it penetrates through the axolemma 54 into the axon 24. The long-acting local anesthetic 80 and the steroid 88 precipitate to form a crystallized compound 82, which creates a prolonged local nerve block 99.

[0117] As shown in FIG. 23, a method incorporating the present invention includes creating an anesthetic nerve block 98. The anesthetic nerve block 98 blocks the electrical potential 56 of the nerve 12 to relieve pain within the living body 10. The method includes dispensing a local short-acting anesthetic agent 76 from a dispenser 102 and positioning the local short-acting anesthetic agent 76 adjacent to the nerve 12. Dispensing a physiological carbonate base 78 from the dispenser 102 and positioning the physiological carbonate base 78 adjacent to the nerve 12. At which point the local short-acting anesthetic agent 76 functions to permeate the physiological carbonate base 78 through the nerve membrane 54 to the axon 24. Dispensing a local long-acting anesthetic agent 80 from the dispenser 102 and positioning the local long-acting anesthetic agent 80 adjacent to the nerve 12. There, the local long-acting anesthetic agent 80 penetrates the nerve membrane 54 and into the axon 24, and the local long-acting anesthetic agent 80 and physiological carbonate base 78 precipitate or deposit and form a crystallized compound 82, producing a long-lasting local nerve block 99.

[0118] The method can further include dispensing epinephrine (adrenaline) 86 from the dispenser 102 to account for intravascular leaks. The method can further include dispensing saline 84 and rinsing the dispenser 102. The method can further include dispensing a steroid 88 from the dispenser 102 to enhance production of precipitated and crystallized compounds 82 and create a prolonged local nerve block 99.

[0119] As shown in FIG. 24, the present invention alternatively includes dispensing a local short-acting anesthetic agent 76 from a dispenser 102 and positioning the local short-acting anesthetic agent 76 adjacent to the nerve 12. Dispensing a local long-acting anesthetic agent 80 from the dispenser 102 and positioning the local long-acting anesthetic agent 80 adjacent to the nerve 12. Dispensing a physiological carbonate base 78 from the dispenser 102 and positioning the physiological carbonate base 78 adjacent to the nerve 12. Wherein the local short-acting anesthetic agent 76 permeates the physiological carbonate base 78 through the nerve membrane 54 to the axon 24. Wherein the local long-acting anesthetic agent 80 permeates the nerve membrane 54 to the axon 24, and the local long-acting anesthetic agent 80 and the physiological carbonate base 78 precipitate or deposit and form a crystallized compound 82, creating a long-lasting local nerve block 99.

[0120] The method can further include dispensing epinephrine (adrenaline) 86 from the dispenser 102 to account for intravascular leaks. The method can further include dispensing saline 84 and rinsing the dispenser 102. The method can further include dispensing a steroid 88 from the dispenser 102 to enhance production of precipitated and crystallized compounds 82 and create a prolonged local nerve block 99.

[0121] The method of the present invention is further described below. 1. A method to produce long-acting nerve blocks in vivo by combining an amide-type long-acting local anesthetic (ALALA) with a physiological base in close proximity to the target nerve. In a #1 long-acting nerve block, achieve precise placement of the block needle adjacent to, but not penetrating, the target nerve. Currently, this is accomplished with ultrasound-guided techniques. b. In nerve block #1, the local anesthetic is the ALALA class, which includes bupivacaine, levobupivacaine, and ropivacaine. c. In the nerve block of #1, the ALALA drug is a physiological base, NaHCO 3 The pH is 0.05, and the precipitate is 2 CO 3 and / or by including NaOH to obtain a high target pH in the final compound injected. d. In the #1 nerve block, the ALALA drug is precipitated by steroids, particularly corticosteroids such as dexamethasone and betamethasone, to produce an ALALA-steroid precipitate. e. In nerve block #1, physiological base and ALALA class drugs are injected sequentially or simultaneously to produce ALALA-carbonate precipitates and crystals. f. These ALALA carbonate precipitates and crystals and ALALA steroid precipitates are produced by precipitation in and around the axons and cell bodies of nerve cells. The ALALA steroid precipitates in g.1c decomposes over time, first to unprotonated ALALA(-), which is able to permeate the axonal sheath, and then to protonated ALALA(+) inside the axon. Protonated ALALA(+) disables the sodium-potassium pump, thereby blocking neurotransmission of pain impulses. The ALALA-carbonate precipitates / crystals in h.1d decompose over time, first to unprotonated ALALA(-) which is able to permeate the axonal sheath, and then to protonated ALALA(+) inside the axon. Protonated ALALA(+) disables the sodium-potassium pump, thereby blocking neurotransmission of pain impulses. In the ALALA-steroid precipitates / crystals of i.1c, the ALALA-steroid precipitates and crystals decompose into the active ALALA drug, providing the patient with analgesia for periods of 120 hours or more. In the ALALA-carbonate precipitate / crystals of J.1d, the ALALA-carbonate precipitate and crystals decompose into the active ALALA drug, providing analgesia to the patient for over 120 hours.

[0122] 2. In the #1 blocking method, a short-acting amide-type local anesthetic (ALA, e.g., lidocaine) first combines with a physiological base to generate unprotonated ALA(-). a. The ALA drug utilized in Solution #1, e.g., lidocaine, does not precipitate in alkaline solutions with a pH <10 (lidocaine precipitates at pH ~11.5). b. In the block method #2, when injected through a block needle precisely adjacent to the target nerve, it easily penetrates the axon sheath of the target nerve, along with it, physiological bases enter the nerve cell (cell body and axon), thereby making the internal environment of the axon alkaline. c. The injection of #2 can further contain adjuvants to increase and enhance the density and longevity of inhibition of impulses by its target nerve, thereby blocking it for longer pain relief. i.#2b injections always contain epinephrine or a similar agent, which, if leaked in minute quantities into the vascular system, can significantly increase pulse rate as a marker of significant vascular penetration. The epinephrine acts as an early warning of unintended vascular access and prevents a dangerous LAST when proceeding with the subsequent injection of the ALALA drug. This is taken as an indication to discontinue the ALALA-carbonate blockade at this point in time. ii.#2b injections include, for example, dexmedetomidine, clonidine, and other alpha 2 An agonist may be included, thereby prolonging and enhancing the concentration (density) of the resulting nerve block. iii.#2b injectates can contain steroids, especially corticosteroids, which precipitate the ALALA drug, creating a depot that separates the ALALA precipitate from the ALALA-carbonate precipitate / crystals. These two depots together increase the density and longevity of the nerve block, creating the longest lasting sensory nerve block. iv.#2b injections may contain an appropriate nonsteroidal anti-inflammatory drug (NSAID) to enhance the sensory nerve block and aid in density and longevity of the nerve block. The v.#2b injectate may include an appropriate N-methyl-D-aspartate (NMDA) antagonist drug, such as ketamine derivatives, dextromethorphan, and others, to enhance the sensory nerve block and aid in the density and longevity of the nerve block. The injection of vi.#2b contains opioid μ of these specific target nerves. 2 -Opioid μ if receptors are known 2 -agonists such as morphine, hydromorphone, meperidine, fentanyl and derivatives.

[0123] 3. Inject #2 alkaline solution flushing solution to flush the single lumen needle prior to injecting any subsequent ALALA medication. Sequential injection of ALALA medication will immediately result in precipitation of ALALA-carbonate in the lumen and subsequent clogging of the lumen, preventing full injection of the desired ALALA dose. This flushing solution is only necessary for single lumen needles and catheters. Both injectates (solutions 1 and 2) must pass through the same needle lumen. b. A bifurcated needle does not allow mixing of these solutions except at the needle tip facing the target nerve, so sediment cannot clog the bifurcated needle. Therefore, irrigation solutions are not necessary for bifurcated needles and bifurcated catheters.

[0124] A mandatory 2 minute wait (test dose) is imposed between injection of solution #1 and before administering solution #2 to ensure that local anesthetic toxicity (LAST) does not occur. This is done by listening to the pulse oximeter and / or monitoring the EKG tracing (or similarly purposive indicator of pulse rate) to find a tachycardia at least 15% greater than baseline (pre-administration). 115% of baseline (pre-administration) indicates that solution #1 has leaked into the vessel due to inadvertent penetration of the vessel during placement of the block needle. This is a strong indication that the block should be discontinued immediately. Subsequent injection of solution #2 after a definite tachycardial outcome would see the patient experience seizures, arrhythmias, cardiac arrest, and death.

[0125] 5. In block #1, after performing the necessary #3 flushing solution (from solution #1) to neutralize the needle lumen pH, and the 2 minute wait for #4 LAST prevention, a second injection of ALALA drug (solution #2) is placed perineurally through the block needle, mixing with the physiological base in and around the nerve (especially within the axon), creating ALALA-carbonate precipitates and crystals.

[0126] 6. Between solution #1 and solution #2 adjuvants can be given depending on their stability in alkaline solutions. a. Epinephrine only should be included in solution #1 along with the ALA drug, with caution against LAST. b. Steroid adjuvants must also be given in solution #1 because they will react with the ALALA drug to produce a precipitate. These adjuvants can be given separately from the physiological base due to the stability between the steroid and the physiological base. c. If necessary, Solution #1 can be separated into separate injections of ALA (eg, lidocaine) and physiological base to maintain the epinephrine integrity of Solution #1. d. Any other compatible adjuvants can be moved to Solution #2 as needed or desired.

[0127] 7. The duration of the nerve block is controlled by the amount of ALALA-carbonate precipitate / crystals produced. This is controlled by the pH of the physiological base concentration in solution #1 with a large pH. When it meets solution #2, it drives a large proportion of the ALALA Drug into ALALA carbonate precipitates / crystals. b. The final target pH for the mixture of solutions #1 and #2 is pH<8.4. c. A pH>8.0 in solution #1 may be necessary depending on the stability of the adjuvant in a single lumen block needle to adequately control the formation of ALALA-carbonate precipitates / crystals at the target nerve site. d. In bifurcated needles, bifurcated catheters and similar dispensing devices, higher non-physiological concentrations of physiological bases can be used in Solution #1, so long as the final mixing of Solutions #1 and #2 still results in a physiological pH <8.4 for the final ALALA-carbonate precipitate / crystals.

[0128] 8. Creating a determinable duration of nerve block can be achieved by varying the amount of ALALA-carbonate precipitate / crystals created by varying the pH of solution #1, as well as the choice and amount of steroid in solution #1. This results in varying the duration of nerve block with two different precipitates (ALALA-carbonate and ALALA steroid) that have different degradation and conversion times back to ALALA(+) within the axon of the nerve block.

[0129] 9. This same approach for amide type local anesthetics can also be applied to ester type local anesthetics because tetracaine has a higher pK than bupivacaine and tetracaine carbonate and tetracaine-steroid precipitation is easier. However, tetracaine is an ester type local anesthetic that decomposes to para-aminobenzoic acid (PABA). PABA is a known irritant and allergen in trace amounts and has the ability to cause anaphylaxis in large doses. Large doses are to be expected in these extended blocks where the duration of analgesia is longer than 72-120 hours. Because of this risk, tetracaine should be avoided for now in these extended blocks. However, in the future, when a safe tetracaine derivative without the generation of PABA or other allergens is discovered, this IP claim will be made.

[0130] Injection of local anesthetics at or around surgical sites for pain relief has been and will continue to be routine hospital protocol for a long time. The desire to extend the duration of local anesthetics is also a goal sought by many during that time. This invention accomplishes that goal by extending the effectiveness of local anesthetics for periods of five days and beyond.

[0131] The ALALA compound of this invention is administered in the same way that local anesthetics are administered today. The ALALA compound is simply substituted at the same step in the current hospital protocol where the local anesthetic currently utilized is administered, following the existing toxicity step. The only departure from the current hospital protocol is that our ALALA compound is administered as a component of a perineural block instead of an epidural block. Also, please note that our new ALALA compound is currently FDA approved. List of reference numbers

[0132] 10 Living organisms 12 Sciatic Nerve 14 Epineurium 16 Perineurium 18 Endoneurium 20 Nodes of Ranvier 22 Myelin sheath 24 Axon 30 Nerve cell body 32 raphe nucleus 34 Dendrites 36 Axon Terminal 38 Oligodendrocytes (Schwann cells) 40 Myelin Packaging 42 Microtubules 44 Microfilament 50 Myelinated neurons (Aδ fibers) 52 Peripheral endings (e.g. skin) 54 Axolemma 56 Unmyelinated neurons (C fibers) 58 Stimulus 60 Unmyelinated neurons (C fibers) 70 Unprotonated Lidocaine 72 Protonated Lidocaine 74 Hydrogen Carbonate (HCO) 3 76 Short-acting local anesthetics: Lidocaine 78 Physiological carbonate bases: sodium bicarbonate, sodium carbonate, sodium hydroxide, dexamethasone, betamethasone and triamcinolone: ​​(possible adjuvant addition) 80 Long-acting local anesthetics: Bupivacaine, Levobupivacaine, Ropivacaine, Tetracaine (ALALA) 82 (ALALA) Carbonate Precipitation 84 Saline 86 Epinephrine 88 Steroids 89 Adjuvant 90 Nodes of Ranvier with extra-axonal deposition of bupivacaine carbonate precipitate 92 Bupivacaine HCO 3 94 Bupivacaine++ OH- + CO 2 96 Bupivacaine - + H 2 O + CO 2 98 Anesthetic Nerve Block 99 Long-acting local nerve blocks / ALALA-carbonate precipitate / ALALA-steroid precipitate 100 Continuous injection system for anesthetic drugs 102 Dispenser 104 Storage Body 106 Transfer body 108 Tip (First) 110 Syringe 112 barrels 114 Plunger 116 needles 118 Multiple barrel membranes for separation 120 Needle for piercing membrane 130 Coaxial needles for parallel injections 132 A combined needle with a common outlet at the tip where mixing of the separate lumens occurs 134 First Dispenser 136 First Storage Body 138 First Transfer Body 140 First Tip (First) 142 Second Dispenser 144 Second Storage Body 146 Second Transfer Body 148 Second Chip (First) 150 The bisecting transfer wall prevents the fluids from mixing except at the tip 108. 152 First Transfer Body 154 Second Transfer Body 160 First Syringe 162 First Barrel 164 First Plunger 170 Second Syringe 172 Second Barrel 174 Second Plunger 180 Third Syringe 182 Third Barrel 184 Third Plunger 186 Tap - Four-way sequential valve 188 Tubes 190 Adjuvant side cylinders for steroids and / or physiological carbonate bases that can be used as precipitating agents for ALALA

[0133] The subject matter of the present invention includes not only what is described above but also what is contained in the appended claims. Although the present invention has been described in some detail in a preferred form, it will be understood that the preferred form is described by way of example only, and that many changes in the details of construction and the combination and arrangement of parts may be made without departing from the spirit and scope of the present invention.

Claims

1. An anesthetic nerve block for relieving pain inside a living body by interrupting the nerve electrical potential, the nerve having an axon covered by a nerve membrane, the anesthetic nerve block comprising the following configurations and technical details: A dispenser comprising a storage body, a transfer body and a tip for positioning adjacent to the nerve. A localized, short-acting anesthetic agent within said storage body. - A physiological carbonate base within said storage body. - The local short-acting anesthetic agent and the physiological carbonate base are provided from the tip of the dispenser, where the local short-acting anesthetic agent functions to penetrate the nerve membrane into the axon with respect to the physiological carbonate base. A localized, long-acting anesthetic agent within said storage body. - The local long-acting anesthetic is provided from the tip of the dispenser, and the local long-acting anesthetic penetrates through the nerve membrane to the axon. The local long-acting anesthetic and the physiological carbonate base precipitate and form a crystallizing compound, producing a long-lasting local nerve block.

2. The anesthetic nerve block of claim 1 , wherein the dispenser comprises a syringe having a barrel that slidably receives a plunger for dispensing through a needle.

3. The anesthetic nerve block of claim 2, further comprising a plurality of barrel membranes thereby maintaining separation of the short-acting local anesthetic, the physiological carbonate base, and the long-acting local anesthetic within the barrel.

4. further comprising a saline solution within said barrel; the plurality of barrel membranes retaining the saline within the barrel between the physiological carbonate base and the long-acting local anesthetic; and 4. The anesthetic nerve block of claim 3, wherein the saline washes the needle after dispensing the short acting local anesthetic and the physiological carbonate base from the needle.

5. The dispenser includes a first dispenser and a second dispenser; the first dispenser having a first storage body, a first transfer body, and a first tip for dispensing the short-acting local anesthetic agent and the physiological carbonate base; and 2. The anesthetic nerve block of claim 1, wherein the second dispenser has a second storage body, a second transfer body, and a second tip for dispensing the long-acting local anesthetic agent.

6. the storage bodies include a first storage body and a second storage body in communication with the transfer body; The transfer body includes a two-part transfer body, the bifurcated transfer body defines a first transfer body and a second transfer body; the first transfer body delivers the short-acting local anesthetic and the physiological carbonate base; and The anesthetic nerve block of claim 1 , wherein the second transfer body delivers the long-acting local anesthetic.

7. the dispenser includes a first syringe, a second syringe and a third syringe; the first syringe having a first barrel that slidably receives a first plunger; the first barrel contains the short-acting local anesthetic agent and the physiological carbonate base 78; the second syringe having a second barrel that slidably receives a second plunger; the second barrel contains a saline solution; the third syringe having a third barrel that slidably receives a third plunger; the third barrel contains the long-acting local anesthetic; a bung connecting the first barrel, the second barrel, and the third barrel with a needle; the stopcock is configured to sequentially dispense the short acting local anesthetic and the physiological carbonate base, the saline solution and the long acting local anesthetic; and 2. The anesthetic nerve block of claim 1, wherein the saline 84 washes the needle after the short acting local anesthetic and the physiological carbonate base are dispensed from the needle.

8. Combining the short-acting local anesthetic with the physiological carbonate base 78 results in an increase in the pH of the short-acting local anesthetic and converts the short-acting local anesthetic into an unprotonated (-) molecule, allowing the short-acting local anesthetic and the physiological carbonate base to more easily locate through the nerve membrane and into the axon; the pH level of said physiological carbonate base determines the amount of precipitation and the size of the crystals in said crystallized compound; By increasing the amount / concentration level of the physiological carbonate base 78, a higher pH can be achieved in the final mixture; Adjusting the amount / concentration level of the physiological carbonate base defines different nerve block durations; and The anesthetic nerve block of claim 1, wherein adjusting the amount / concentration level of the physiological carbonate base defines different nerve block concentrations.

9. The anesthetic nerve block of claim 1, wherein the short-acting local anesthetic is lidocaine.

10. 2. The anesthetic nerve block of claim 1, wherein the long-acting local anesthetic is selected from the group consisting of bupivacaine, levobupivacaine, ropivacaine and tetracaine.

11. 2. The anesthetic nerve block of claim 1, wherein said physiological carbonate base is selected from the group consisting of sodium bicarbonate, sodium carbonate and sodium hydroxide.

12. further comprising a steroid in said storage body 104; The long-acting local anesthetic and the steroid cause the precipitation to form the crystallized compound, creating a prolonged local nerve block; and 2. The anesthetic nerve block of claim 1, wherein the steroid is selected from the group consisting of dexamethasone, betamethasone and triamcinolone.

13. An anesthetic nerve block for relieving pain inside a living body by interrupting the nerve electrical potential, the nerve having an axon covered by a nerve membrane, the anesthetic nerve block comprising the following configurations and technical details: A dispenser comprising a storage body, a transfer body and a tip for positioning adjacent to the nerve. A localized, short-acting anesthetic agent within said storage body. - steroids within said storage body. - The local short-acting anesthetic and the steroid are provided from the tip of the dispenser, where the local short-acting anesthetic acts on the steroid to penetrate through the nerve membrane to the axon. A localized, long-acting anesthetic agent within said storage body. - The local long-acting anesthetic is provided from the tip of the dispenser, and the local long-acting anesthetic penetrates through the nerve membrane to the axon. The local long-acting anesthetic and the steroid precipitate and form crystallized compounds, producing a long-lasting local nerve block.

14. 14. The anesthetic nerve block of claim 13, wherein the steroid is selected from the group of dexamethasone, betamethasone and triamcinolone.

15. 1. A method for producing an anesthetic nerve block, the anesthetic nerve block interrupting the electrical potential of a nerve to relieve pain within a living body, the nerve having an axon covered by a nerve membrane, the method comprising the steps of: - Dispensing a localized, short-acting anesthetic agent from a dispenser and positioning the localized, short-acting anesthetic agent adjacent to a nerve. dispensing physiological carbonate base from a dispenser and positioning the physiological carbonate base adjacent to a nerve, where the localized short-acting anesthetic agent acts on the physiological carbonate base to penetrate through the nerve membrane to the axon; and Dispensing a local long-acting anesthetic from a dispenser and positioning the local long-acting anesthetic adjacent to a nerve, where the local long-acting anesthetic penetrates the nerve membrane to the axon, and the local long-acting anesthetic and the physiological carbonate base form a precipitated or deposited and crystallized compound to produce a long-lasting local nerve block.

16. 16. The method of claim 15, further comprising the step of dispensing epinephrine from a dispenser to account for intravascular leaks.

17. 16. The method of claim 15, further comprising the steps of dispensing saline and cleaning the dispenser.

18. 16. The method of claim 15, further comprising the step of dispensing steroid from a dispenser to enhance production of said precipitate and crystallize compounds and create a prolonged local nerve block.

19. 1. A method for producing an anesthetic nerve block, the anesthetic nerve block interrupting the electrical potential of a nerve to relieve pain within a living body, the nerve having an axon covered by a nerve membrane, the method comprising the steps of: - Dispensing a localized, short-acting anesthetic agent from a dispenser and positioning the localized, short-acting anesthetic agent adjacent to a nerve. - Dispensing a local long-acting anesthetic agent from a dispenser and positioning the local long-acting anesthetic agent adjacent to a nerve. Dispensing physiological carbonate base from a dispenser and positioning the physiological carbonate base adjacent to a nerve, where the local short-acting anesthetic agent permeates through the nerve membrane to the axon with respect to the physiological carbonate base, where the local long-acting anesthetic agent permeates through the nerve membrane to the axon, and where the local long-acting anesthetic agent and the physiological carbonate base form a precipitated or deposited and crystallized compound to produce a long-lasting local nerve block.

20. 20. The method of claim 19, further comprising the step of dispensing epinephrine from a dispenser to account for intravascular leaks.

21. 20. The method of claim 19, further comprising the steps of dispensing saline and cleaning the dispenser.

22. 20. The method of claim 19, further comprising the step of dispensing steroid from a dispenser to enhance production of said precipitate and crystallize compounds to create a prolonged local nerve block.

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