JP2008543851A - Emetic capsules - Google Patents

Abstract

  The present invention is a capsule containing an emetic, which can enclose a drug, and even if a human takes an excessive dose of the emetic encapsulated drug, the drug is absorbed into the body. The amount of emetic and drug is determined so that the number of capsules required to cause vomiting when taken is less than the number of capsules required to cause overdose when taken. Provide capsules.

Description

  This application claims priority from US Provisional Patent Application No. 60 / 690,023 (filed Jun. 13, 2005), the contents of which are hereby incorporated by reference.

Background of the Invention Regardless of whether a drug is legally prescribed by a physician or can be purchased over-the-counter, all drugs have the potential for misuse. When taken in excess, drugs that are normally considered safe can cause death or severe physical damage.

  Accidental and intentional overdose or death from drug overdose is a serious problem. Humans attempt to commit suicide, take drugs and often succeed. Humans with depression and with suicide attempts are also at increased risk of drug overdose. Drug addicts may ingest and consume large amounts of drugs to cause serious damage to their bodies in order to obtain an effect that changes mind and mood. The child opens any drug container, even a tamper-evident container, and accidentally ingests and consumes the drug without knowledge of the consequences.

  Accidental drug overdose can be the result of misuse of prescription drugs or over-the-counter drugs (such as pain relievers and cold medicines). Between 1970 and 2000, about 131,000 people died from accidental drug overdose. Mortality from side effects of taking the right drug at the right dose was low (3%), but 97% of deaths were due to drug misuse, including accidental drug intake or accidental overdose intake. According to the National Institute of Drug Abuse, in 1992, nearly 6,000 deaths were the result of accidental overdose of psychotropic drugs and other drugs. Antidepressants: GSK's WELLBUTRIN® and PAXIL® (paroxetine), Eli Lilly's PROZAC® (fluoxetine), Pfizer's ZOLOFT® (sertraline), Solvay's LUVOX® (Fluvoxamine), Forest Laboratories' CELEXA® (Citalopram) and LEXAPRO® (Ecitalopram), Wyeth's EFFEXOR® (Venlafaxine), Bristol-Myers Squibb Patients treated with SERZONE (R) (Nefazodone) and Organon's REMERON (R) (Mirtazapine) are at increased risk of suicide attempts and suicide.

  Therefore, there is a great demand for dosage forms that prevent accidental or intentional drug overdose.

  It is known in the art that emetics can be incorporated into drug compositions or mixed with drugs. After ingestion, the drug and emetic are simultaneously released into the stomach. However, this requires the development of formulations and compositions that are compatible or otherwise suitable for use with both drugs and emetics, and furthermore, drugs and emetics are compatible with each other. It needs to be tolerant. Furthermore, the combination of emetic and drug in the composition releases the emetic and drug as soon as they are ingested, so a dangerous or toxic amount of drug can be absorbed by the body before the drug is vomited There is a danger.

  U.S. Pat.Nos. 4,175,119 and 4,529,583 (incorporated herein by reference) are medicines that prevent accidental or intentional drug overdose by coating tablets or capsules with emetics An exemplary composition is disclosed. However, this requires the use of coating equipment that is not used by health care professionals.

  Accordingly, there is a need for an emetic dosage form that can be used for the delivery of a wide range of drugs and that allows for flexible administration of drugs and emetics.

  Furthermore, there is a need for an emetic dosage form that can be used for the delivery of a wide range of drugs and that allows customized administration of drugs and emetics to individual patients.

  In addition, there is a need for methods of manufacturing and administering emetic dosage forms that allow health care professionals to adjust different amounts of different drugs to individuals who may be taking excessive amounts of the drug. Exists.

  Furthermore, there is a need for a method of customizing emetic dosage forms that induce vomiting before the drug can be absorbed by humans and before overdose can occur.

SUMMARY OF THE INVENTION The present invention is a capsule comprising an emetic and can encapsulate a drug, where a human overdose the emetic encapsulated drug. The number of capsules required to cause vomiting when taken is such that the human will return an amount of drug that can cause overdose to the body before it is absorbed. Provide capsules that define the amount of emetic and the amount of drug to be less than the number of drugs.

  The present invention is therefore directed to a capsule containing an emetic.

  In one embodiment of the invention, an emetic embedded piece is formed from a mixture comprising a matrix, a plasticizer and an emetic.

  In another embodiment of the invention, the emetic encapsulating piece is formed from a mixture comprising a matrix, a plasticizer and an emetic, and the piece also has a sub-compartment that holds a single or a mixture of different emetics. .

  In another aspect of the invention, the emetic encapsulating capsule is formed of at least a first emetic encapsulating piece and a second capsule piece. An emetic encapsulating capsule can also be formed by encapsulating a drug in a sub-chamber of an emetic encapsulating piece, the emetic being encapsulated within the main chamber of the capsule.

  In yet another aspect of the present invention, emetic-encapsulated capsules are usually safe if taken properly (i.e., by prescription or instructions), but potentially toxic or latent if taken in excess. Used in methods of inducing vomiting in individuals attempting to prevent injury or death from accidental or intentional overdose of drugs that are potentially lethal, toxic, or lethal Is appropriate to do.

  In yet another embodiment of the invention, the drug is encapsulated in an emetic encapsulating capsule to form an emetic encapsulating drug.

  In yet another embodiment, central and / or gastrointestinal emetics are used as emetics.

  In yet another embodiment, an emetic having both central and gastrointestinal effects is used in the emetic encapsulating capsule or emetic encapsulating piece.

  In yet another aspect of the present invention, the emetic encapsulating capsule or piece can include different amounts of emetic having a specific emetic dose so that a suitable emetic encapsulating capsule or piece is It can be selected for a specific drug, for a specific drug dose, and / or for a specific patient.

  In yet another aspect, different colored emetic encapsulated capsules or pieces may display different amounts of emetic contained in the emetic encapsulated capsules or pieces.

  In yet another aspect of the present invention, the emetic encapsulating capsule or piece may comprise different types of emetics or a mixture of emetics, so that suitable emetic encapsulating capsules or pieces are for a particular drug, It can be selected for a specific drug dose or for a specific patient.

  In yet another aspect, different colored emetic encapsulated capsules or pieces may indicate different types of emetics present in the emetic encapsulated capsules or pieces.

  In yet another embodiment of the present invention, the laxative may be replaced with the emetic.

  In yet another embodiment of the invention, the capsule may contain a flavor and a flavoring agent.

  In yet another aspect of the invention, when the capsule contains an inert substance and when taken in a normal amount, the emetic can pass through the digestive tract with the help of the inert substance, The emetic is not substantially absorbed by the body. However, when the capsule is ingested in an amount that induces vomiting, the inert substance does not prevent vomiting.

  Other objects of the present invention will be apparent from the general description herein.

DESCRIPTION OF THE DRAWINGS FIG. 1 is an emetic encapsulating capsule according to the present invention.

Detailed Description of the Invention Capsules 2 for taking drugs, as shown in Figure 1, are well known in the art. Capsules, i.e. hard gelatin or hard gel capsules, generally consist of two pieces, i.e. male piece 4 and female piece 6, where both pieces act cooperatively to engage each other, generally Fits the male piece 4 into the female piece 6. In general, each of the two pieces has an outer periphery, a thickness, and an inner periphery. The inner circumference 6A of the female piece 6 is slightly smaller than the outer circumference 4A of the male piece 4, so that the male piece meshes with the female piece and forms a sealed condition to prevent the capsule contents from leaking. If desired, the two pieces may be of the same or similar size with means for engaging each other, which means are known in the art.

  In general, a single compartment 10 is formed in the capsule when the two pieces are engaged with each other. As described in FIG. 1, it is known in the art that each capsule piece can also include a separate smaller compartment 12 (shown as a sub-compartment in male piece 4); In this case, if one of the two pieces has a sub-compartment, the capsule has a main compartment 10 and a sub-compartment 12, and one piece if the pieces each have a sub-compartment. Main compartment and two sub-compartments. For example, the sub-compartment can be formed by insertion of an internal separating shell for a desired material, such as an emetic or drug. The sub-compartment 12 may be filled with the same material as the main compartment 10 or with a different material.

  Capsule and capsule piece compositions are well known in the art. Capsules and capsule pieces typically include a matrix and a plasticizer.

  A matrix is a substance that can form a sheet or film. The matrix comprises gelatin, cellulose and cellulose derivatives, carbohydrate polymers, polyvinyl polymers, and other materials known in the art, such as a capsule shell comprising hydroxypropyl methylcellulose as disclosed in US Pat. No. 5,756,123 See, capsules having hydrocolloids as a matrix disclosed in US Pat. No. 6,214,376, and thermally gelled cellulose ethers disclosed in US Pat. No. 4,001,211. The preferred matrix for the present invention is based on gelatin.

  A plasticizer is a substance that increases or decreases the flexibility or toughness of the matrix. Glycerin, sorbitol and other materials known in the art are used as plasticizers. See, for example, capsules having water-soluble cellulose derivatives as matrices, plasticizers and co-plasticizers as disclosed in US Pat. No. 5,264,226.

  In the present invention, one or more matrix materials and one or more plasticizer materials may be used to form capsules.

  Other desired ingredients known in the art such as dyes, flavors, fragrances, surfactants, disintegrants, pH modifiers and other additives can also be mixed therein. Such materials are known in the art.

  Methods for making capsules are well known in the art. For example, the pins may be immersed in the capsule composition, and the capsule thickness can be changed by changing the temperature of the pins. See, for example, US Pat. No. 2,526,683 and US Pat. No. 4,817,367. Depending on the method of manufacture, further substances can also be incorporated into the capsule composition, including lubricants known in the art.

  Tamper proof capsules and methods for making tamper proof capsules are well known in the art. Gelatin locking capsules are known in the art. For example, US Pat. No. 4,040,536 discloses gelatin capsules with locks.

  The capsules in the present invention may also be soft gel capsules, ie capsules for taking liquid drugs, and may be filled by injection or other means known in the art. Compositions of soft gel capsules, their production and filling methods are known to those skilled in the art.

  As is known in the art, an appropriate amount of drug is the appropriate amount or form of drug taken in accordance with prescribing information and instructions, regardless of prescription or over-the-counter sales. Excess drug intake occurs when the drug is ingested beyond prescribing information and instructions, which is also referred to as overdose. Overdose occurs when a drug or other chemical is ingested, which causes physical injury, injury, disease or death. Drug overdose can occur in different people after taking different amounts of drug. For example, human A causes overdose after ingestion of 10 g of drug, but human B does not cause overdose even after ingestion of 10 g of the same drug.

  The capsules in the present invention are various drugs known in the art to be at risk when misused or accidentally or intentionally overdose, eg less than 50 times the recommended dose, eg recommended It is used to encapsulate drugs that can cause death or serious injury to humans at doses less than 20 times or less than 10 times the dose. The drugs include acetylsalicylic acid, acetaminophen, vitamins, as well as psychotropic, antihypertensive, anticonvulsant, amphetamine, antimicrobial, antibiotic, antiviral, antiretroviral, antifungal, antifungal Depressant, stimulant, antihistamine, anxiolytic, tricyclic compound, tranquilizer, benzodiazepines, hypnotic, mood stabilizer, codeine, selective serotonin reuptake inhibitor, antiallergic, phenothiazine, chemotherapeutic, amine , Monoamine oxidase inhibitors, anti-carcinogens, analgesics, muscle relaxants, ergot preparations, anticholinergics, anti-inflammatory agents, anti-gout preparations, soporfic, hormone preparations, appetite suppressants, Including but not limited to analgesics, muscle relaxants, and opioids.

  Liquid formulations of drugs are also known in the art. In the present invention, the drug in the liquid formulation can be encapsulated in a capsule by methods known in the art. In the present invention, the drug in the liquid formulation can also be encapsulated in a soft gel capsule by methods known in the art.

  Emetics and the emetic response caused by such emetics are well known in the art. For example, emetics are disclosed in US Pat. No. 4,269,820. Emetics can be roughly divided into two classes: chemicals that produce an emetic effect by acting on the “vomiting center” in the bone marrow, and chemicals that themselves act directly on the stomach. Certain emetics can also act on the bone marrow and stomach (eg, emetine and cephaeline). Representative examples of emetics known in the art are methylcephaeline, cephaeline, emetine hydrochloride, psychotrine, O-methylpsychotriline, emethamine, ipecamine, hydro-ipecamine, ipecacunhun acid ), Apomorphine, ammonium carbonate, copper (II) sulfate, tartar emetic, zinc sulfate, black mustard, sanguinaria, copper sulfate, eucalyptol, eucalyptus oil, glycynhiza, guaiacol, lobelia, potassium iodide, Including, but not limited to, Senega, Teleben, terpine hydrate, thyme, caffeine, sodium bicarbonate salt and mixtures thereof.

  In the present invention, an emetic is any substance that has the action of propeling the contents of the stomach into the mouth, that is, emesis and vomit. The emetic dose is the amount of emetic that induces or causes vomiting when taken. The emetic dose causes some gastric content vomiting, preferably most gastric content vomiting, more preferably substantially all gastric content vomiting.

  Desirable emetics include emetics that cause an emetic response when taken orally and act on the stomach. Desirable emetics do not cause nausea when taken at doses below the emetic dose, but immediately cause vomiting when taken at the emetic dose. Desirable emetics are taken immediately upon taking the emetic dose, ie within 1 hour of taking the emetic dose, preferably within 45 minutes, more preferably within 30 minutes, and even more preferably taking the emetic dose. Vomiting occurs within 20 minutes or within 15 minutes using an emetic dose. If drug overdose causes loss of consciousness, to avoid inhalation into the lungs, it is preferred that the person vomit before losing consciousness. If a second substance that blocks the emetic response, ie alcohol, is taken before, with or after the emetic dose, it is preferred to cause vomiting before impaired ejection.

  In the present invention, the emetic encapsulating piece is a capsule piece having a matrix, a plasticizer and at least one emetic. The emetic encapsulating piece can be formed by various methods known to those skilled in the art. When manufacturing an emetic encapsulating piece so that the piece can contain a predetermined amount of emetic (expressed as a percentage per weight or mass of the piece), a predetermined amount of emetic is added to the matrix and plastic. Add to agent composition. The mixture of emetic, matrix and plasticizer is then formed into male or female capsule pieces.

  Alternatively, the capsule piece may have a sub-compartment and the emetic encapsulating piece may be formed by adding one or more emetics to the sub-compartment. The sub-compartment is then sealed to form an emetic encapsulating piece. The emetic encapsulating piece can also be formed from a mixture of matrix, plasticizer and emetic in addition to the emetic in the sub-compartment. The emetic in the mixture and the emetic in the sub-compartment may be the same or different emetics.

  In the present invention, the emetic encapsulating capsule is a capsule having a matrix, a plasticizer and at least one emetic.

  Alternatively, the emetic encapsulating capsule may be formed of a first emetic encapsulating piece and a second capsule piece. The emetic encapsulated piece and the emetic non-encapsulated piece may consist of different matrices and plasticizer compositions so that the piece dissolves or ruptures in the digestive tract at different times or at different rates.

  Alternatively, the emetic encapsulating capsule is formed of two emetic encapsulating pieces. The emetic encapsulating piece may consist of different matrix and plasticizer compositions so that the piece dissolves or ruptures at different rates or at different times in the digestive tract.

  Alternatively, when the drug is contained in the sub-compartment of the capsule piece, an emetic can be included in the main compartment of the capsule to form an emetic encapsulating capsule.

  Alternatively, when the drug is contained within a sub-compartment of the capsule piece formed from a matrix, plasticizer and emetic mixture, additional emetic is contained within the capsule's main compartment and the emetic is encapsulated Capsules can be formed. The emetic in the mixture can be the same or different emetic from the emetic contained in the main compartment.

  In the present invention, an emetic encapsulating piece comprising one matrix and a plasticizer composition can be used with an emetic encapsulating piece having a different matrix and plasticizer composition. Differences in composition will allow the capsules to dissolve or rupture at different rates or at different times in the digestive tract.

  In the present invention, one or more emetics can be used to form one emetic encapsulating piece. In another aspect of the present invention, an emetic encapsulating capsule may be formed of a plurality of emetic encapsulating pieces containing different emetics.

  In the present invention, it is possible to produce emetic encapsulating capsules having different colors according to the amount of emetic present. For example, emetic capsules containing 100 mg of emetic are black; emetic capsules containing 200 mg of emetic are blue; emetic capsules containing 300 mg of emetic are red; contain 400 mg of emetic Emetic capsules can be yellow; emetic capsules containing 500 mg of emetic can be white.

  In another aspect of the invention, the emetic encapsulating piece may be a different color depending on the amount of emetic present. For example, an emetic encapsulating piece containing 50 mg of emetic is black; an emetic enclosing piece containing 100 mg of emetic is blue; an emetic enclosing piece containing 150 mg of emetic is red; and contains 200 mg of emetic The emetic encapsulated piece can be yellow; the emetic encapsulated piece containing 250 mg of emetic can be white. Thus, an emetic encapsulating capsule containing 150 mg of emetic is a black and blue emetic encapsulating piece (50 mg in black emetic embedding piece and 100 mg in blue emetic embedding piece); The emetic encapsulating capsules include black and white emetic encapsulated pieces (50 mg in black emetic encapsulated pieces and 250 mg in white emetic encapsulated pieces), or 2 red emetic encapsulated pieces (2 150 mg) in a red emetic embedding piece.

  In another aspect of the invention, the emetic encapsulating piece and capsule may be of different colors depending on the emetic or combination of emetics encapsulated in the piece or capsule. For example, an emetic encapsulating piece containing zinc sulfate is green; an emetic enclosing piece containing apomorphine is yellow; an emetic enclosing piece containing zinc sulfate and apomorphine is red; and is formed of an apomorphine enclosing piece and a zinc sulfate enclosing piece The emetic encapsulating capsules become yellow and green emetic encapsulating pieces.

  In one embodiment of the invention, the drug is filled into emetic capsules, optionally with excipients such as fillers, binders, disintegrants, lubricants, colorants, or other conventional adjuvants.

  Many drugs known to those skilled in the art are provided in tablet dosage forms containing a particulate form of several components. Tablets are also known in the art to include excipients such as fillers, binders, disintegrants, lubricants, colorants, or other conventional adjuvants.

  In one embodiment of the invention, the tablet is “milled” with any excipients in the tablet, such as fillers, binders, disintegrants, lubricants, colorants, or other conventional adjuvants, It encloses in this emetic embedding capsule.

  The present invention can also be used to encapsulate tablets, capsules, or soft gel capsules containing one or more drugs and excipients. As a result, the drug is first contained in an emetic non-encapsulated capsule or tablet, which is then encapsulated in the emetic encapsulated capsule. The matrix and plasticizer selected to form the emetic encapsulating capsule can be a composition that is substantially different from the matrix and plasticizer encapsulating the tablet or capsule containing the drug and excipients. Here, the compositional differences allow for dissolution or rupture in the digestive tract at different rates or at different times.

  In the present invention, the amount of drug taken by the patient can be independent of the amount of emetic encapsulated within the capsule. One skilled in the art can readily determine the amount of drug required for a particular treatment. One skilled in the art can also readily determine the amount of drug that a patient can take without overdose. One skilled in the art can also determine the type and amount of specific emetics or combinations of emetics that are required to induce vomiting by ingestion by humans. Accordingly, those of ordinary skill in the art will provide patients with a sufficient amount of emetic to induce vomiting before or at the same time they take enough of the drug to cause overdose. An emetic encapsulating piece or capsule may be selected for ingestion.

  When taken by a patient orally, when the emetic-encapsulated capsule reaches the stomach, the emetic-encapsulated capsule dissolves or ruptures and the emetic is released into the stomach. Once an emetic dose has been taken, vomiting will occur before any significant amount of drug is released or absorbed, as vomiting expels the drug from the body.

  The amount of emetic in each emetic encapsulating capsule is such that the amount of emetic released will not induce vomiting. When the appropriate amount of drug is taken, no vomiting response is elicited. However, vomiting occurs when excessive drugs are taken.

  The present invention is intended to provide health care professionals (eg, physicians and pharmacists) with the flexibility to formulate and administer a wide range of drugs to individual patients.

  In the present invention, taking a certain emetic-encapsulating capsule does not cause nausea or nausea. However, taking more emetic capsules can cause nausea, nausea and vomiting. Desirable emetics do not cause nausea or nausea prior to taking the emetic dose.

  The effective amount of emetic encapsulated in an emetic encapsulating capsule can be calculated by various methods.

  In one method, the drugs have a specific dosage form and amount (ie, the same drug has different doses in a tablet or capsule). The drug also has some level of overdose or toxic dose. It can be readily determined how many tablets or capsules containing the drug need to be ingested prior to overdose or toxic effects in humans. Also, it can be easily determined how many emetics are needed to induce vomiting in the same person. Then, the amount of emetic taken before humans take a sufficient amount of medication to cause overdose causes vomiting, or a sufficient amount of medication for humans to overdose Capsules containing a specific amount of emetic are selected from the group of emetic encapsulated capsules so that vomiting occurs immediately after ingestion.

  For example, suppose that the drug is formulated in a dosage form containing 50 mg in one tablet or capsule and overdose occurs at 10 mg / kg. Then, a 70 kg person needs to take 700 mg, or 14 tablets, before overdose. Assume that an emetic induces a response in humans when 5 g is ingested. Then, at least 5 g of emetic should be included in 14 capsules. The pharmacist receives the prescription, recognizes that the person is at risk of suicide, and chooses to pack the drug in an emetic capsule. The pharmacist has the choice of emetic encapsulating capsules containing 100 mg, 200 mg, 300 mg, 400 mg or 500 mg of emetic per capsule. The pharmacist selects a 400 mg emetic capsule and packs the drug into a 400 mg emetic capsule so that if 14 drugs are ingested, 5.6 g of emetic is ingested and 70 kg To induce vomiting in humans. Alternatively, the pharmacist may select a 500 mg emetic encapsulating capsule so that taking 10 drugs induces vomiting.

  In another method, the drugs have a specific dosage form and amount (ie, the same drug has different doses in tablets or capsules). The drug also has a certain level of overdose or toxic dose. It can be easily determined how many tablets or capsules containing a particular amount of drug need to be taken before an overdose or toxic effect occurs in humans. Also, it can be easily determined how many emetics are necessary to induce vomiting in the same person. The type or mixture of emetic taken prior to human being able to take a sufficient amount of drug to cause overdose will then cause vomiting or sufficient for humans to overdose. Capsules containing one type of emetic or mixture of emetics are selected from the group of emetic encapsulated capsules so that vomiting occurs immediately after taking the amount of drug.

  For example, suppose the drug is formulated in a 50 mg dosage form in tablets or capsules and overdose occurs at 10 mg / kg. A 70 kg person needs to take 700 mg, or 14 tablets, before overdose. Thus, the emetic should be effective when taken at least 14 capsules. The pharmacist receives the prescription, realizes that the person is at risk of committing suicide, or has a small child, or is confused about his dose, and chooses to pack the drug in an emetic capsule . Pharmacists have the choice of emetic encapsulating capsules containing different emetics. Three different emetic encapsulating capsules containing the same amount of emetic are available to encapsulate the drug: first emetic including a first emetic that elicits a response in humans when ingested 3 g An encapsulated capsule; a second emetic encapsulating agent containing a second emetic that elicits a response in humans when ingested 5 g; a third comprising a third emetic that elicits a response in humans when ingested 9 g Emetic capsules. Each emetic capsule contains only 400 mg of the emetic. If the pharmacist takes 14 tablets, 5.6 g of the first emetic is taken and induces vomiting in a 70 kg person, or 5.6 g of the second emetic is taken and in a 70 kg human. The first or second emetic capsule will be selected to induce vomiting.

  In another method, the drug is formulated in a single dosage form over a period of time, for example, one capsule or tablet once a day, or X capsules or tablets over a period of time. Suppose that taking Y tablets or capsules at the same time causes an overdose of a drug that poses a risk of death or serious harm to the patient. Thus, emetic-encapsulated capsules are selected so that the emetic-encapsulated capsules contain sufficient emetic to induce vomiting if a number of capsules close to the overdose (Y) capsules are taken Is done. Accordingly, suitable emetic encapsulating capsules comprise at least 1 / Y of the emetic dose required for an emetic response and less than 1 / X or within the range of 1 / X to 1 / Y.

  For example, suppose a drug is formulated as one tablet at a certain time. Suppose a pharmacist recognizes that an overdose will occur if two tablets are taken. Therefore, the pharmacist selects an emetic encapsulating capsule that is at least half the emetic dose but less than one of the emetic dose.

  For example, suppose a drug is prescribed as 3 tablets at a certain time. Suppose that the pharmacist recognizes that an overdose will occur if four tablets are ingested. Therefore, the pharmacist selects an emetic encapsulating capsule that is at least 1/4 of the emetic dose and less than 1/3 of the emetic dose.

  For example, suppose a drug is formulated as 3 tablets over a period of time. Suppose that the pharmacist recognizes that overdose occurs if six tablets are ingested. Therefore, the pharmacist will not cause vomiting if 3 encapsulated capsules are ingested, but an emetic encapsulated capsule having a quarter of the emetic dose will be selected and 4 or more encapsulated capsules will be ingested. If vomiting occurs and an emetic encapsulated capsule with 1/5 of the emetic dose is selected and more than 5 encapsulated capsules have been ingested, vomiting occurs and 1/6 of the emetic dose Select emetic capsules with at least 1/6 to less than 1/3 of the emetic dose so that vomiting occurs if 6 or more capsules are ingested To do.

  In another method, the drug can include one or more ingredients that can cause overdose. Ingredients that are most toxic or likely to cause overdose should be used by selecting specific emetic capsules.

  In the present invention, it is convenient for a pharmacist or other health care professional to have one or a series of tables that can be easily used when selecting a specific emetic encapsulating capsule for encapsulating a drug. possible. The table identifies emetics or combinations of emetics and emetic doses according to other characteristics that affect human weight or emetic doses. Further tables may also include other characteristics that affect human weight or emetic dose, and specific emetics or combinations of emetics according to specific drugs.

  In another embodiment of the invention, the emetic composition is one or more drugs mixed, or a tablet, capsule or one containing one or more drugs, by any of the spray coating methods known in the art. It can be spray coated onto a soft gel. The emetic composition includes an emetic and a matrix such that the composition is spray coated onto a drug, tablet, capsule or soft gel. Suitable emetic compositions or spray solutions have one or more emetics, a matrix, and a solvent in which the emetic or matrix is dissolved or suspended. After the emetic composition is sprayed onto the capsules, the matrix and the emetic are coated onto the capsules when the solvent is evaporated. Solvents are well known in the art and may include plasticizers and / or organic solvents.

  Certain emetics can themselves be recognized as toxic. While one object of the present invention is to prevent accidental or intentional drug overdose, the compositions provided herein are also in a prescribed amount, ie every hour, 4 hours a day. It should be safe to take once, every day, every week, according to a doctor's prescription or according to an appropriate dose. Therefore, all the aforementioned compositions and emetics also pass through the digestive tract when the combination of emetic and inert substance is ingested, and vomiting occurs when a sufficient amount of the emetic-encapsulated capsule is ingested. As may be induced, it may be combined with one or more inert substances known in the art that are substantially inert in the gastrointestinal environment. However, when the emetic encapsulating capsule is ingested in an appropriate amount, the emetic is not absorbed into the body and passes through the digestive tract and is discharged from the body. Inert materials suitable to be added in the present invention are known in the art. See, for example, US Pat. No. 4,529,583, incorporated herein by reference.

Example 1
Carrageenan is a polysaccharide hydrocolloid extracted from seaweed. There are several forms of carrageenan, including the kappa, eta and lambda forms. κ-carrageenan is known to form a gel in the presence of potassium cations. η-carrageenan is known to form a gel in the presence of calcium cations. Carrageenan capsules can be manufactured by the following steps.

1. κ-carrageenan or a mixture of κ-carrageenan and η-carrageenan / gelatinized salt / mannan gum / xanthan gum (if these substances are present) at ambient temperature or at least slightly higher (higher temperature) Of course, which is usually advantageous for the physical dissolution of most substances) and dispersed in a plasticizer (or a mixture of plasticizers);

2. Aqueous solutions are prepared by dissolving other additives (eg maltodextrin, gum arabic and protein) in water (preferably at about ambient temperature, but slightly higher or lower temperatures may also be used) ;

3. Add the aqueous solution to the kappa-carrageenan / plasticizer mixture to form a working composition;

4. The working composition is preferably stirred with a temperature above 130 ° F. to below the boiling point of the working mixture, preferably between 135 and 210 ° F., more preferably about 160 to 180 ° F. Heating to a temperature between

5. Add emetic to the working composition; and

6. The heated working composition containing the emetic is then transferred to a conventional gelatin encapsulator for processing (the film is cast by casting the solution on a cooled rotating drum (eg metal, eg steel). Formed, sent to a series of roller-counterrotating dies, cut and filled into capsules of various sizes).

The following working composition may be produced. The components of the composition are expressed in weight percent.

  The amount of emetic is per piece. It can be added to the working composition so that capsule pieces containing 1 mg to 500 mg of emetic can be formed.

Example 2
Acetaminophen is a commonly prescribed and over-the-counter drug that is often misused and causes overdose resulting in liver toxicity and death. Liver toxicity can occur after ingestion of 7.5 g acetaminophen and death can occur after ingestion of 15 g acetaminophen. Acetaminophen can be purchased in various dosage forms, for example 80, 325, 500 and 650 mg per tablet or capsule. Depending on the dose, different emetic encapsulating capsules can be selected to encapsulate acetaminophen. For example, it is necessary to take 94 80 mg acetaminophen tablets before overdose; 15 500 mg acetaminophen tablets need to be taken before overdose; cause overdose Before, it is necessary to take 12 650 mg acetaminophen tablets. Thus, when 650 mg of acetaminophen is encapsulated in an emetic encapsulating capsule, the emetic encapsulating capsule should be selected from the group that induces vomiting prior to taking 12 capsules. When encapsulating 500 mg of acetaminophen in an emetic capsule, the emetic capsule should be selected from the group that induces vomiting prior to taking 15 capsules. When 80 mg of acetaminophen is encapsulated in an emetic capsule, the emetic capsule should be selected from the group that induces emesis before ingesting 94 capsules.

  For example, if acetaminophen is formulated at a 325 mg dose, overdose by taking the acetaminophen will therefore occur when taking at least 12-3 325 mg tablets or capsules. An emetic-encapsulating capsule encapsulating an emetic that causes vomiting when 5 g of the emetic is ingested is selected to encapsulate the acetaminophen. Therefore, when 7.5 g acetaminophen is ingested (23 tablets ingested), 5 g emetic is also ingested and the emetic encapsulating capsule should contain at least 217 mg emetic to induce vomiting There is. Vomiting will occur before a substantial amount of acetaminophen is released into the stomach and absorbed by the body.

Example 2A
The pharmacist may purchase a capsule piece containing the embodiment shown in FIG. 1, ie, a predetermined amount of emetic, and have a wide range of inventory. The pharmacist has a choice of emetic encapsulating pieces including 100 mg, 150 mg, 200 mg, 250 mg and 300 mg of emetic. When there is a prescription for taking 325 mg of acetaminophen, the pharmacist has the choice of an emetic encapsulating piece with 250 mg or 300 mg of emetic to encapsulate the acetaminophen. The pharmacist adds the acetaminophen to the emetic encapsulating piece and seals the capsule with a second capsule piece. Alternatively, the pharmacist can select 100 mg and 150 mg emetic encapsulation pieces to encapsulate 325 mg acetaminophen to form the emetic encapsulation capsule.

Example 2B
The acetaminophen manufacturer can market a 325 mg acetaminophen dose in an emetic encapsulating capsule and label it “emetic containing”.

Example 3
Alprazolam (marketed by Pfizer as XANAX®) is often a misused prescription and is dispensed in 2 mg tablets. The pharmacist has the option of crushing the tablet and encapsulating the powder in an emetic encapsulated capsule, or encapsulating the entire tablet in an emetic encapsulated capsule.

Example 4
Fluoxetine hydrochloride (marketed by Eli Lily and Company as PROZAC® and SARAFEM®) is a frequently misused prescription drug and is formulated in 10 mg tablets. Although taking 520 mg of fluoxetine hydrochloride has been reported to cause death, other side effects occur more quickly. Due to the toxicity of low doses of fluoxetine hydrochloride, which is substantially less than lethal, the selected emetic capsules contain only a few capsules, ie 4, 10, 20, 25, 30 or 40 capsules. Ingestion induces vomiting. Fluoxetine hydrochloride is a widely prescribed drug and capsule pieces are manufactured with fluoxetine hydrochloride contained within the sub-compartment of the piece. The pharmacist then adds the emetic to the capsule piece having a sub-compartment that includes fluoxetine hydrochloride, and then the emetic-encapsulated capsule is a non-emetic encapsulated piece, an emetic encapsulated piece, or a sub-compartment. Emetic encapsulated capsules are made by sealing with another piece with fluoxetine hydrochloride contained within.

Example 5
Diazepam (marketed by Roche Pharmaceuticals as VALIUM) is a benzodiazepine derivative that is often misused. The oral LD50 of diazepam is 720 mg / kg in mice and 1240 mg / kg in rats. Depending on the severity of the condition, VALIUM can be prescribed 10 mg four times a day. VALIUM is formulated in 2 mg, 5 mg and 10 mg tablets. The pharmacist recognizes that the patient has a history of drug misuse and chooses to enclose diazepam in an emetic capsule. The pharmacist also recognizes that the patient has a tendency to tamper with the capsule without permission and selects an emetic encapsulating capsule that has a tamper-evident lock.

Example 6
Hydrocodone bitartrate (sold by Abbott Laboratories as VICODIN®, VICODIN ES® and VICODIN HP®) is an opioid analgesic and antitussive that is often misused. Hydrocodone bitartrate is often taken with acetaminophen (ie VICODIN® containing 5 mg hydrocodone bitartrate and 500 mg acetaminophen per tablet; 7.5 mg hydrocodone bitartrate and 750 mg per tablet) VICODIN ES® with acetaminophen; and VICODIN HP® with 10 mg hydrocodone bitartrate and 660 mg acetaminophen per tablet. Hydrocodone bitartrate and acetaminophen can cause toxicity or death. Patients are often advised not to take twice the amount of VICODIN because of the toxicity of hydrocodone bitartrate. Therefore, health care professionals are more interested in hydrocodone bitartrate to cause toxicity or death rather than acetaminophen.

  Zinc sulfate heptahydrate causes vomiting when ingested 0.6 g. In order to cause vomiting when a double dose of VICODIN is ingested, the emetic capsule should contain between .3 and .6 g of zinc sulfate.

Example 7
Triazolm (sold by Pharmacia & Upjohn as HALCION®) is a relaxing agent that is misused. Overdose can occur after taking 2 mg. HALCION® is provided as .125 mg and .25 mg tablets. Because of the efficacy of triazolam and an individual can take more than 4 tablets at a time (4 .25 mg tablets are 2 mg triazolam that can cause overdose), emetic-encapsulated capsules are more than 2 Sufficient emetic should be included to induce vomiting as soon as many emetic capsules are ingested. Therefore, triazolam is encapsulated using an emetic encapsulating capsule containing from 0.3 to 0.6 g of zinc sulfate so that vomiting does not cause vomiting when taking one capsule.

Example 8
Methylphenidate hydrochloride (commercially available from McNiel Consumer Healthcare as CONCERTA®) is a central nervous system stimulant that is often misused. CONCERTA® tablets use osmotic pressure to deliver methylphenidate hydrochloride at a controlled rate. CONCERTA® tablets are similar to traditional tablets containing an osmotically active three-layer core covered with an immediate release drug protective membrane and covered by a semipermeable membrane. The three layers consist of two drug layers containing drug and excipient and a push layer containing osmotically active ingredients. There is a hole drilled with a precision laser at the end of the drug layer of the tablet. After ingestion, the drug protective film dissolves, providing the first dose of methylphenidate. Water penetrates into the tablet core through the membrane, the excipient swells as an osmotically active polymer, and methylphenidate is released from the hole. CONCERTA tablets contain biologically inert ingredients that pass through the digestive tract as they are and are excreted in the stool with insoluble core components. Accordingly, CONCERTA® tablets cannot be crushed and encapsulated in emetic encapsulating capsules. However, the pharmacist is an emetic encapsulating capsule (shown in FIG. 1) having a sub-compartment containing an emetic and is used to make an emetic encapsulating capsule containing an appropriate amount of the emetic. Encapsulated capsules can be selected.

  Alternatively, CONCERTA® manufacturers will place CONCERTA® in the sub-compartment of the capsule piece so that the pharmacist can enclose an appropriate amount of emetic in the main compartment of the capsule. You can choose to encapsulate. This gives the pharmacist the freedom to adapt the emetic dose for the individual. The appropriate amount of emetic does not cause vomiting when the drug is taken in the proper amount, and the number of emetic capsules taken to induce vomiting is taken to cause overdose of the drug It is a specific amount that is less than the number of capsules containing the agent.

Example 9
Bupropion hydrochloride (marketed by GlaxoSmithKline as WELLBUTRIN® and ZYBAN®) is an antidepressant that is often misused. WELLBUTRIN® is formulated as a 75 mg or 100 mg tablet and ZYBAN® is formulated as a 150 mg tablet. In a population of individuals who have experienced drug misuse, a single dose of 400 mg WELLBUTRIN produces mild amphetamine-like activity. Bupropion is associated with seizures in approximately 0.4% of patients treated with doses up to 450 mg / day, which is more than four times that of other marketed antidepressants. The estimated seizure incidence rate of WELLBUTRIN increases about 10 times between 450 mg / day and 600 mg / day. To reduce the risk of seizures, it is recommended that a single dose of WELLBUTRIN or ZYBAN not exceed 150 mg. Thus, when a pharmacist packs ZYBAN in an emetic-encapsulated capsule or emetic-enclosed piece, thereby taking two 150 mg doses, he causes vomiting to avoid amphetamine-like activity and reduce the risk of seizures. The pharmacist also packs 100 mg WELLBUTRIN tablets into emetic capsules, which causes vomiting to reduce the risk of seizures when 4 tablets are taken, but when 2 tablets are taken Does not cause vomiting and may produce amphetamine-like activity.

  The items shown here are for illustration only and are not limiting. While particular embodiments have been shown and described, it will be apparent to those skilled in the art that changes and modifications can be made without departing from the broader aspects of the invention. The actual scope of protection sought is intended to be defined in the claims when there is a reasonable view based on the prior art.

FIG. 1 is an emetic encapsulating capsule according to the present invention.

Claims (35)

Emetics;
A matrix; and a plasticizer;
Capsule piece containing. The capsule piece of claim 1, further comprising an inert material. The matrix and the plasticizer form a shell having separate compartments, the emetic is contained within the compartment, and the shell can mesh with a second capsule piece. 2. Capsule piece according to item 1. Capsule piece according to any one of claims 1-2, formed from a mixture of the matrix, the plasticizer and the emetic. A capsule comprising the first capsule piece and the second capsule piece according to any one of claims 1 to 4. A capsule comprising two capsule pieces according to any one of claims 1 to 4. 7. A capsule according to any one of claims 5 to 6, comprising or suitable for containing a unit dosage form of a drug, wherein the weight of the emetic is 1 / X the emetic dose that induces emesis. To 1 / Y, where X is the number of unit dosage forms of the drug prescribed to be taken within a specified time, and Y is overdose if taken within the same time Capsule, which is the number of unit dosage forms of the drug. The capsule according to any one of claims 5 to 7, wherein the emetic is in an amount of 1/2 to 1/20 of the dose that induces emesis in a 70 kg human. The capsule according to any one of claims 5 to 8, wherein the emetic is selected from the group consisting of a central emetic and a gastrointestinal emetic. The capsule according to any one of claims 5 to 9, wherein the emetic is a central emetic. The capsule according to any one of claims 5 to 9, wherein the emetic is a gastrointestinal emetic. The emetic is emetine, methyl cephaeline, cephaeline, emetine hydrochloride, psychotrine, O-methyl cycotrin, emethamine, ipecamine, hydro-ipecamine, ipecacunhun acid, apomorphine, ammonium carbonate , Copper (II) sulfate, tartar emetic, zinc sulfate, black mustard, sanguinaria, copper sulfate, eucalyptol, eucalyptus oil, glycynhiza, guaiacol, lobelia, potassium iodide, senega, teleben, terpine water 12. Capsule according to any one of claims 5 to 11, selected from the group consisting of Japanese, thyme, caffeine, lobelia inflata, and sodium bicarbonate, and combinations thereof. (i) a drug and (ii) an emetic encapsulated drug comprising the capsule according to any one of claims 5 to 12, wherein the number of capsules required to cause vomiting when taken is said drug when taken Drugs that determine the amount of emetic and the amount of drug so that it is less than the number of capsules required to cause overdose. An emetic encapsulated drug comprising the drug encapsulated in the capsule according to any one of claims 5 to 12. 15. An emetic encapsulated drug according to any one of claims 13 or 14, wherein the drug is a drug that causes death or severe injury in humans at less than 50 times the recommended dose. The drug is acetylsalicylic acid, acetaminophen, vitamins, psychotropic drug, antihypertensive agent, anticonvulsant, amphetamine, antimicrobial agent, antibiotic, antiviral agent, antiretroviral agent, antifungal agent, antidepressant , Stimulants, antihistamines, anxiolytics, tranquilizers, benzodiazepines, hypnotics, mood stabilizers, codeine, selective serotonin reuptake inhibitors, antiallergic drugs, phenothiazines, chemotherapeutic drugs, amines, monoamine oxidase inhibitors Agents, anticarcinogens, analgesics, muscle relaxants, ergot preparations, anticholinergics, anti-inflammatory agents, antigout preparations, soporfic, hormone preparations, appetite suppressants, analgesics, muscle relaxation The emetic-encapsulated drug according to claim 13, 14 or 15, which is selected from the group consisting of an agent and opioids, and combinations thereof. The emetic-encapsulated drug according to claim 16, wherein the drug is acetaminophen. The emetic-encapsulated drug according to claim 16, wherein the drug is codeine. The emetic-encapsulated drug according to claim 16, wherein the drug is acetylsalicylic acid. The emetic-encapsulated drug according to claim 16, wherein the drug is a tricyclic compound. The emetic-encapsulated drug according to claim 16, wherein the drug is an antidepressant. 17. The emetic encapsulated drug according to claim 16, wherein the drug is a selective serotonin reuptake inhibitor. The emetic-encapsulated drug according to claim 16, wherein the drug is a monoamine oxidase inhibitor. The emetic-encapsulated drug according to claim 16, wherein the drug is a benzodiazepine. The emetic-encapsulated drug according to claim 16, wherein the drug is a hypnotic. The emetic-encapsulated drug according to claim 16, wherein the drug is an opioid. The emetic-encapsulated drug according to claim 16, wherein the drug is an analgesic. The emetic-encapsulated drug according to claim 16, wherein the drug is an antipsychotic drug. 29. The emetic embedded drug according to any one of claims 13 to 28, wherein the emetic is a substance capable of inducing vomiting. The emetic is emetine, methyl cephaeline, cephaeline, emetine hydrochloride, psychocotin, O-methyl cycotrin, emethamine, ipecamine, hydro-ipecamine, ipecacic acid, apomorphine, ammonium carbonate, copper (II) sulfate, tartar emetic Agent, zinc sulfate, black mustard, red mustard, copper sulfate, eucalyptol, eucalyptus oil, licorice, guaiacol, lobelia, potassium iodide, senega, teleben, terpine hydrate, thyme, caffeine, and sodium bicarbonate salt, and its 30. The emetic encapsulated drug of claim 29, selected from the group consisting of combinations. The emetic is emetine, cephaelin, emethamine, ipecamine, hydro-epecamine, ipecic acid, apomorphine, ammonium carbonate, copper sulfate (II), tartar emetic, zinc sulfate, black mustard, red crab, copper sulfate, eucalyptol, eucalyptus 31. The emetic encapsulated drug of claim 30, selected from the group consisting of oil, licorice, guaiacol, lobelia, potassium iodide, senega, terben, terpine hydrate, thyme, caffeine, and sodium bicarbonate. Encapsulating the drug in a capsule according to any one of claims 5 to 12 so as not to induce vomiting when taking an appropriate amount of drug and to induce vomiting when taking an excessive amount of drug A method of preventing or reducing the risk of drug overdose, comprising: Encapsulating the drug in a capsule according to any one of claims 5 to 12 so as not to induce vomiting when taking an appropriate amount of drug and to induce vomiting when taking an excessive amount of drug A method of preventing or reducing the overdose of a drug administered to a patient considered to be at risk of accidental or intentional overdose of the drug, comprising: 32. A method for inducing vomiting, comprising: taking an emetic dose of an emetic contained in an emetic encapsulated drug according to any one of claims 13 to 31. 32. An emetic encapsulated drug dosage form according to any one of claims 13 to 31 so as not to induce vomiting when taking an appropriate amount of drug and to induce vomiting when taking an excess of drug. A method of preventing or reducing the overdose of a drug administered to a patient considered to be at risk of accidental or intentional overdose of a drug, comprising administering a drug.

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