JP2009511191A - Orally administered drug package method - Google Patents

Abstract

A pharmaceutical delivery package containing two or more different pharmaceutically active ingredients in a given unit dose, wherein the different pharmaceutical ingredients are (a) combined in a single delivery package and (b) Isolated from each other in a package, the package containing a core having a first pharmaceutically active ingredient, the core being at least partly by a capsule having a second pharmaceutically active ingredient A pharmaceutical delivery package characterized in that it is surrounded.
[Selection] Figure 1

Description

  The present invention relates to a packaging technology for pharmaceuticals and medical drugs. The invention is particularly useful for packaging a combination of two or more pharmaceuticals or drugs for the treatment of the same condition or for the treatment of complications. Although the present invention has been described for such uses, other uses may be contemplated.

  Two or more co-administered in a unit dosage form as opposed to administering a certain number of separate doses of two or more pharmaceuticals at regular intervals It has been recognized in the field of pharmacy that it is convenient to have the following pharmaceutically active ingredients, and the applicant's prior US Pat. Nos. 6,428,809 and 6,702,683 are hereby incorporated by reference. (Patent Document 2), the specification of US Patent Application No. 10 / 756,124 (Patent Document 3) and the specification of Patent Application No. 10 / 479,438 (Patent Document 4) currently pending, and US Provisional Patent Application No. It is described in the specification (Patent Document 5) of 60 / 727,029. Benefits for patients and physicians include: (1) minimizing or eliminating local and / or systemic side effects; (2) more effective pathological symptoms (3) improve the treatment of many drugs; and (4) care for the disease as a whole and make it more convincing for the patient, while reducing the number of doctor visits, This can reduce hospitalization treatments and make patients better and reduce costs.

  In the above-referenced US Pat. Nos. 6,428,809 and 6,702,683 (Patent Document 2) of the Applicant referred to above, they are separated from each other in an easily ingestible pharmaceutical delivery package. It is described to package a medicinal product or drug having two or more active activities. Therein, the pharmaceutical delivery package is, for example, in the form of a tablet or capsule. Applicants' above patent discloses and claims various drug combinations.

U.S. Pat.No. 6,428,809 U.S. Patent No. 6,702,683 U.S. Patent Application No. 10 / 756,124 U.S. Patent Application No. 10 / 479,438 US Provisional Patent Application No. 60 / 727,029

  The present invention provides improved techniques for the pharmaceutical delivery package described in the applicant's above-referenced patent document.

  In a specific aspect of the invention, a predetermined dose combination drug therapy delivery package is provided that is easy to manufacture. In particular, in a specific embodiment of the invention, a predetermined unit dose contains two or more different pharmaceutically active ingredients, and the different pharmaceutically active ingredients are (a) a single delivery package. And (b) a pharmaceutical delivery package that is isolated from each other within the package, the package containing a core having a first pharmaceutically active ingredient, the core comprising a first A pharmaceutical delivery package is provided, characterized in that it is at least partially surrounded by a capsule having two pharmaceutically active ingredients. The pharmaceutically active ingredient here is a single pharmaceutical ingredient, optionally combined with an appropriate excipient, or one or more pharmaceutical ingredients, optionally combined with an appropriate excipient. Defined as one of those being The present invention provides a combined drug therapy that includes more efficient treatment of complications, treatment with multiple drugs, reduction of side effects, replacement therapy and known drug interactions. It provides a unique and advantageous combination of drugs that address or overcome one of several related problems.

  In one specific embodiment of the invention, the delivery package is designed to be able to release two or more pharmaceutical ingredients substantially simultaneously. In another specific embodiment of the invention, the pharmaceutical delivery package can release two or more pharmaceutical ingredients separately or release two or more pharmaceutical ingredients at a time lag. can do. For example, the present invention relates to a combination drug containing a pharmaceutical ingredient that provides a therapeutic method in combination with drugs for the treatment of diabetes such as diabetes and hyperlipidemia or diabetes and hypertension, or treatment with multiple drugs. A therapeutic delivery package is provided. In another embodiment of the invention, a combination therapy is provided for the treatment of hyperlipidemia and hypertension. In a particular embodiment of the invention, the active ingredients are separated from each other by a physical barrier, which destroys the package or divides it into two halves, which are substantially divided into the halves. The package is characterized in that the pharmacotherapeutic activity is divided between those.

  As used herein, the term “predetermined dose combination drug therapy delivery package” means that two or more drug components are packaged together in a single dosage form and from each other. It is isolated. Each of the drug constituents may contain a pharmaceutically active ingredient. Also, one of the drug constituents may contain a pharmaceutically active ingredient, while the other of the drug constituents achieves the effects of other ingredients, such as via an acid-base reaction. Or substances that enhance or inhibit other ingredients in a known and predictable manner, or substances that inhibit or enhance the absorption time or uptake of other ingredients, or through enzymatic activity It contains substances that can suppress or increase the metabolism of the substance and absorb other components. Also, in another specific embodiment of the invention, the pharmaceutical delivery package comprises two or more packaged in a form such that one or more of the components are released at different sites in the digestive tract. Contains more pharmaceutical ingredients. Further features and advantages of the present invention will become apparent from the following description of the specification with reference to the accompanying drawings. In the drawings, like reference numerals denote like parts.

1A-1H illustrate a method of making a combination drug therapy delivery system according to one specific embodiment of the present invention.
2A-2E illustrate a method of making a combination drug therapy delivery system according to a second specific embodiment of the present invention.
3A-3B illustrate how to divide the combination drug therapy delivery system of FIG. 2 or split it into two halved doses.
4A-4C illustrate a specific embodiment of a combination drug therapy delivery system capable of releasing a pharmaceutically active ingredient over time in accordance with the present invention.
5A-5l illustrate a specific embodiment of a combination drug therapy delivery system.

  Reference is first made to FIGS. 1A-1B, which illustrate a technique for creating a combination drug therapy delivery system according to one specific embodiment of the present invention. Referring to FIG. 1A, a core 10 containing a controlled amount of a first pharmaceutical ingredient is molded with a pharmaceutically active ingredient together with a filler, a binder, and tablets, capsules in a known manner. Or it is manufactured as a tablet, a capsule, or a caplet by a usual method by making it a caplet. The core tablet, capsule or caplet 10 is then coated with a barrier material 12 such as gelatin, starch or cellulose such as hydroxypropylmethylcellulose, indicated by shading at 12. In another case, the core 10 is a two-piece capsule 14 made of gelatin such as, for example, Press-Fit Gelcaps available from Capsugel, Inc., Morris Plains, NJ. , 16 can be sealed.

  Referring to FIGS. 1C-1D, a controlled amount of a second pharmaceutically active ingredient 18 is packed into the bottom of the shell 20 on one side of the capsule. A shell 20 on one side of the capsule sized to cover the core 10 is assembled to the core 10 and fixed in place by shrinking or press-fitting, This results in a drug therapeutic delivery system containing the two medicinal products shown.

  The pharmaceutically active ingredients 10 and 18 may be in the form of a powder, including a fine powder, a coarse powder, or a powder containing several different size fractions in the particle fraction. It may also be in the form of pellets, beads or tablets as well. In addition, the pharmaceutically active ingredients 10 and 18 may be in liquid or semi-liquid form, which helps to ensure an accurate dosage. The solution is preferably made as a mixture of drug and solvent, or as a solvent solution of the drug, together with a solvent that quickly evaporates or with a liquid formulation that quickly solidifies after being placed in one of the capsules. Can be. In addition, the liquid formulation of the drug can be used to create an adhesive force between the components of the combination drug therapy delivery system according to a specific embodiment of the present invention. When the solvent is completely evaporated, a strong bond can be formed between the components of the combination drug therapy delivery system, such as the shell 20 on one side of the capsule and the part 14 of the capsule.

  In another specific embodiment of the invention, the pharmaceutically active ingredient 18 in powder form is packed into a shell 20 on one side of a capsule, and a small amount of a suitable solvent, such as water, is placed in the shell 20 on one side of the capsule. Into a viscous mixture of the pharmaceutically active ingredient 18 and the solvent. When the solvent is completely evaporated, a strong bond can be formed between the components of the combination drug therapy delivery system, such as the shell 20 on one side of the capsule and the part 14 of the capsule.

  Referring to another specific embodiment of the present invention shown in FIGS. 1E and 1F, the pharmaceutically active ingredient of the liquid formulation on the outside of the part 14 of the capsule by dip coating as shown in FIG. 1E And then coated with a shell 20 on one side of the capsule as shown in FIG. 1F. When the solvent is completely evaporated, a strong bond can be formed between the components of the combination drug therapy delivery system, such as the shell 20 on one side of the capsule and the part 14 of the capsule. Referring to FIG. 1G, another specific embodiment of the present invention is shown in which a greater amount of a pharmaceutically active ingredient of a semi-liquid formulation is placed in a shell 20 on one side of a capsule. is there.

  Referring to FIG. 1H, another specific embodiment of the present invention is shown in which two or more different pharmaceutically active ingredients are incorporated into a combination drug therapy delivery system in accordance with the present invention. It is put.

  In another case, as shown in FIGS. 2A-2E, the second pharmaceutically active ingredient 18 is divided into two capsule unilateral shells 20, 24, which are incorporated into the core 10 and joined together. Press fit (shrink) or shrink. If desired, the shells 20, 24 on one side of each capsule may contain controlled amounts of different drugs. Referring to FIGS. 3A-3B, it is shown how the combined drug therapy delivery system of FIG. 2 can be split or split into two halves.

  In another specific embodiment of the present invention, a combination of pharmaceutically active ingredients is placed in a combination drug therapy delivery system and the ingredients are released simultaneously or at a time lag in the patient's digestive tract. And / or allows it to be released in an extended manner. For simultaneous release, two or more pharmaceutically active ingredients placed in a combination drug therapy delivery system are effectively released as the capsule or capsule component dissolves in the patient's digestive tract. To be harassed. For applications that release over time, the design and wall thickness and / or wall composition can be used to make specific capsule assemblies, including solubility in acidic and / or alkaline media. In which one of the components is released before or after another component or components. More specifically, the pharmacologically active ingredient is released over time by varying the composition of the capsule wall, porosity, hardening of the capsule material, and wall thickness.

  As shown in FIG. 4A, as the compartment 51 is protected by the walls of the compartments 50 and 52, the capsule walls of the compartments 50 and 52 are dissolved more rapidly, so that the inside of the compartments 50 and 52 The pharmaceutically active ingredient in is first released.

  Looking at FIGS. 4B and 4C, some of the compartments of the combined drug therapy delivery system may be described with a single thicker wall or a plurality of thicker walls, for better understanding. Shown as having a wall. As shown in these drawings, the thicker wall has a higher thickness, a different wall material, or both, thereby controlling the dissolution rate of the wall. It shows that it is going slower. Also, if the compartment walls shown in FIGS. 4B and 4C are of a composition of different materials, the corresponding compartment will be resistant to immediate dissolution, thus the corresponding compartment. The release of the pharmaceutically active ingredient from is delayed. This will result in the desired delayed release or release at different locations along the digestive tract. Furthermore, the wall of the compartment that does not dissolve in the acidic environment of the stomach can be made to dissolve in a more neutral to alkaline environment of the small intestine, and thus in the small intestine. The pharmaceutically active ingredient contained in the can be released. Thus, while one or more of several pharmaceutically active ingredients contained in the combination drug therapy delivery system of the present invention can be delivered to the stomach, another pharmaceutically active ingredient or more Can be delivered to the small intestine.

  In the above specific embodiment, the pharmaceutically active ingredients are released at the same time, are released with a time difference, and can be released at different places. In addition to delivery to different parts of the gastrointestinal tract, it is possible to combine pharmaceutically active ingredients that have a fast and delayed action, such as pain medications. Another application of the present invention is, for example, to combine delivery such that a patient takes a first pharmaceutically active ingredient before ingesting a meal, while taking a second pharmaceutically active ingredient after a meal. is there. The combination drug delivery system is taken prior to eating a meal, but the second pharmaceutically active ingredient is delayed and released. Another specific embodiment of the invention is that if released simultaneously, by chemical interaction between components in the vicinity of the component being dissolved, a change in pH or other parameter, or by another component Including a combination therapeutic delivery system in which the pharmaceutically active ingredient is differentially released because the pharmaceutically active ingredient interacts with an ingredient that has an adverse effect on action or absorption Yes.

  Turning to FIGS. 5A-51, the combination drug therapy delivery system assembly can be further reinforced. Alternatively, the components can be joined using a tight fit of the components of the assembly. In one specific embodiment, the restraint ring (lock ring) or occlusal connection (the restraint ring-concave combination) is as shown in FIGS. 5A, 5B, 5C and 5D, and the polymer band is shown in FIG. As shown in 5F and 5G. In addition, a mechanism containing a restraining recess for secure fitting as shown in FIGS. 5H and 51 allows the combined drug therapy delivery system of the present invention to be reliably assembled. ing. Other methods are possible which include forming a bond between the constructs as described above and shown in FIGS. IE and IF above. There are still other ways to ensure assembly of the combination drug delivery system, such as a hydroalcoholic seal or other liquid using a shrink wrap-like detention mechanism (lock mechanism) or the like. Includes a seal. The mechanisms that ensure assembly of the combination drug therapy delivery system are not limited to those described above, and other mechanisms are possible.

  As described in our above-mentioned patents and patent applications, it is advantageously used to treat complications, to treat with many drugs and / or to reduce the side effects of treatment There are many combinations of medicines that can be made. For example, it is reported that 80 +% diabetic patients are also hypertensive patients. Hyperlipidemic patients also often have diabetes at the same time. Antidiabetic agents commonly used to treat diabetes in this way, for example, insulin sensitivity improvers such as sulfonylurea, meglitinide, biguanide, and thiazolidinedione (thiazolidinedione) Antidiabetic agents such as insulin sensitizers or alpha-glucosidase inhibitors can be combined with drugs useful for treating hypertension or hyperlipidemia. For example, a dose of sulfonylurea (e.g., Glipizide) can be administered in a single delivery system with a dose of statins (e.g., atorvastatin, fibrate, bile acid inhibitors). sequestrant (eg, Cholestipol), cholesterol absorption inhibitor or niacin. Similarly, sulfonylureas can be combined with bile acid inhibitors. Similarly, medicines for treating diabetes include ACE inhibitors, angiotensin II receptor antagonists, calcium antagonists (calcium channel blockers, calcium blockers), beta-blockers (beta- can be combined with a blocker), or a diuretic. An example is a combination agent of a biguanide [eg, metformin] administered in combination with a calcium channel blocker (eg, amlodipine). Another example would be a combination of a meglitinide agent (eg, repaglinide) and an angiotensin II receptor antagonist (eg, Losartan).

Also, the combination of medicines can be selected based on the following criteria:
-Possibility of pharmcodynamic interaction Affinity to the same receptor or similar effects on physiological function, with or without the mechanism of action Combinations of medications that can be squeezed may be selected.
-Potential pharmacokinetic interactions Pharmacokinetic interactions can be revealed in several ways, some of which are in vivo monitoring. Some methods are not. One drug is selected based on its ability to change the absorption or excretion of another drug, its ability to change its distribution into one or more tissues, or its ability to change the pattern or rate of metabolism. Can do. Drugs compete for binding of serum proteins, resulting in increased circulating free quantity and tissue uptake of one drug.

-The possibility of toxic interactions (e.g. if the target organ is similar for each drug with respect to toxicity).
The dose that does not have any predetermined effect on one or both drug products may be reduced and / or more severe toxicity in the affected organs should be considered.
-Safety margin for each drug If one or more of the drugs has a narrow margin of safety (ie, there is an amount that causes significant toxicity near the expected clinical dose) At that time, it is necessary to consider the possibility of drug interaction.

-Consideration should be given to the possibility of the drug competing for or altering the activity or endogenous level of the same enzyme or other intracellular molecules (eg, two prooxidants) Combined administration can reduce the endogenous level of glutathione)
-Possible chemical interaction One drug can chemically modify another drug (e.g. one drug can oxidize, methylate, or ethylate other drugs) ). This may be a new molecule with new toxicity. However, these effects can be largely avoided by delaying the release of the drug.
-One drug may harm the effect of another drug

  Various specific embodiments of the present invention will be further described in the following examples, which are not intended to be limiting:

(1) Formulation Example # 1: Enalapril maleate ^{1 and} its analogs and isomers are ACE inhibitors used in the treatment of hypertension. This drug is the next without clinically significant side effects, and is an analog and isomer of beta adrenergic-blocking agents, methyldopa, nitrate, calcium blocker ( Can be used together with calcium blocking agents, Hydralazine ⁶ , Prazosin ⁷ or Digoxin ⁸ . One or more of these drugs may be used to treat diabetes such as sulfonylureas, meglitinides, biguanides, insulin sensitizers or alpha-glucosidase inhibitors as described above. Can be packaged with medicines.

(2) Formulation Example # 2: Hypoglycemic drugs such as metformin HCl ^{2 and} its analogs and isomers can be packaged together with an angiotensin converting enzyme inhibitor (ACE inhibitor) as described above.
(3) Formulation Example # 3: The diabetic drug as described above in Formulation Example # 1 or # 2 is used together with an angiotensin II receptor antagonist such as losartan potassium ³ and / or valsartan ⁴ as described above. Can be packed into package.

(4) Formulation Example # 4: The above-mentioned antidiabetic drug is packaged together with a sympathetic β receptor blocker such as bisoprolol fumarate ⁵ or metoprolol succinate ⁶ as described above. Can be packed into.
(5) Formulation example # 5: The above-mentioned diabetes drug should be packaged together with a calcium channel blocker such as amlodipine ⁷ or Nifedipine ⁸ as described above in formulation example # 1 or # 2. Can do.

(6) Formulation Example # 6: The diabetic drug as described above can be packaged together with a peripheral sympathetic receptor blocking agent (Periferal Adrenergic Blocking Agent) such as prazosin hydrochloride ⁹ .
(7) Formulation Example # 7: The above-mentioned diabetes drugs are packaged together with a central adrenergic receptor stimulant such as Methyldopa ¹⁰ or Clonidine ¹¹ be able to.

(8) Formulation Example # 8: A biguanide agent such as metformin ¹⁴ can be packed in a package as described above together with a sulfonylurea agent such as glipizide ¹⁵ .
(9) Formulation Example # 9: A biguanide such as metformin ¹⁴ can be packaged as described above with a thiazolidinedione agent such as rosiglitazone maleate ¹⁶ .

(10) Formulation Example # 10: A biguanide such as metformin ¹⁴ can be packaged as described above together with an α-glucosidase inhibitor such as Cerivastatin ¹⁷ .
(11) Formulation Example # 11: Fast-acting oral insulin can be packaged as described above along with sustained-release oral insulin.

The drug delivery system of the present invention is a combination of three drugs such as a beta blocker, methyldopa, nitrates, calcium channel blocker, hydralazine ¹² , prazosin ¹³ and digoxin ¹⁴ in combination with an ACE inhibitor. A combination of many drugs also makes this possible.

(12) Formulation Example # 12: Diabetes drugs can be packaged together with ACE inhibitors and beta-blockers.
(13) Formulation Example # 13: Diabetes drugs as described in Formulation Example # 1 or # 2 are HMG-CoA reductase inhibitors (HMG) such as Simvastatin ³⁵ , Atorvastatin ³⁶ , or Pravastatin ^37. -CoA reductase inhibitor) and can be packaged with bile acid inhibitors such as colestipol hydrochloride ³⁸ .
(14) Formulation Example # 14: Diabetes as described in Formulation Example # 1 or # 2 can be packaged with a HMG-CoA reductase inhibitor and with a niacin compound.
(15) Formulation Example # 15: Diabetes drugs as described in Formulation Example # 1 or # 2 are lipids such as HMG-CoA reductase inhibitors or Formulation Example # 14 and Gemfibrozil ³⁹ Can be packaged with a drop-in medicine.

  In the above specific embodiments of the present invention, specific pharmaceutical combinations that have been isolated from each other are described, but some of the pharmaceutical combinations listed above may also be chemically. It will be appreciated that if there is no problem with the interaction, it can be blended and packed into a package in a single tablet, capsule or caplet.

  Other specific embodiments of the present invention include at least one pharmaceutically active ingredient and at least one substance which is a pharmaceutically active ingredient or a non-pharmaceutical ingredient and is minus the first pharmaceutically active ingredient. Combinations with those that relieve the effects of the above, those that promote / enhance the action of the first pharmaceutically active ingredient, or those that promote the general health and good condition of the patient who has taken the first pharmaceutically active ingredient It is for things. The following non-limiting examples are illustrative of specific embodiments of the invention:

  Example 16: A combination of a first pharmaceutically active ingredient that causes side effects and administration of a second pharmaceutically active ingredient that mitigates the side effects of the first pharmaceutically active ingredient is placed in a single delivery package. Yes. Specific examples include a first pharmaceutically active ingredient having side effects such as constipation, nausea, gas / abdominal bloating, heartburn, pain or convulsions; and alleviating the above side effects of the first ingredient, for example, The second pharmaceutically active ingredient for treatment with laxative treatment with drugs, treatment for nausea with drugs, antigas and antiabdominal bloating treatment with drugs, antigastric acid treatment with drugs, treatment with pain relieving agents and muscle relaxants It is done. More specific examples include a pharmacological treatment for pain that causes constipation and nausea, and an oral narcotic, for example, combined with a second component containing a stool softener or an anti-nausea component. It is done.

  Example 17: In another specific embodiment of the present invention, the first pharmaceutically active ingredient controls or stops the action of the first ingredient after the time necessary for the action of the first ingredient. In combination with a second pharmaceutically active ingredient. As an example, a combination of an anticancer drug such as immediate-release methotrexate and a `` quencher '' substance such as sustained-release L-leukovorin may be used for this combination drug treatment. It is advantageously transported in the delivery system.

  Example 18: In another specific embodiment of the invention, the first pharmaceutically active ingredient is used to promote the solubility and / or absorption of the first pharmaceutically active ingredient, Combined with a substance that optimizes the pH in the immediate vicinity of the first pharmaceutically active ingredient. In addition, controlling and / or neutralizing gastric acid to slow down the decay of the first pharmaceutically active ingredient will improve the bioavailability of the first pharmaceutically active ingredient. Examples of substances that control pH include, but are not limited to, compounds having a pH buffering capacity known in the art.

  Example 19: In another specific embodiment of the invention, the first pharmaceutically active ingredient that is soluble in fat contains a second pharmaceutically active ingredient or oil for better drug solubility and absorption. It is combined with the substances that are

  Example 20: In another specific embodiment of the invention, the first pharmaceutically active ingredient is combined with an enzyme, and the enzyme promotes absorbability and / or bioavailability of the pharmaceutically active ingredient, or Reduce side effects.

  Example 21: In another specific embodiment of the invention, the first pharmaceutically active ingredient is combined with a nutraceutical (such as a functional food) or a vitamin. Examples include, but are not limited to, (i) Nexium (esomeprazole) and vitamin B, which interfere with vitamin B 12 absorption that occurs only at low pH by altering the pH of the stomach. Combinations with groups and (ii) combinations of antiviral pharmaceutical active ingredients with vitamin C or multivitamin supplements.

  Example 22: In another specific embodiment of the present invention, the first pharmaceutically active ingredient comprises a surfactant that promotes absorption, conversely promotes, or inhibits absorption at some point in the digestive tract. Combined.

  Example 23: In another specific embodiment of the invention the first pharmaceutically active ingredient is combined with a sleep improving agent.

  Another specific embodiment of the present invention is the same symptom or disease such as infectious disease, metabolic disease, cardiovascular disease, pain, cancer, transplantation related treatment, gastrointestinal disease, respiratory disease, autoimmune disease, vaccine, etc. Directed against a combination of at least two pharmaceutically active ingredients in the same class of medicinal products (treatment by taking many drugs). Examples that are not intended to impose the following limitations illustrate that for this specific embodiment of the present invention:

  Example 24: Combining an anti-infective pharmaceutically active ingredient with an example containing at least two formulated antibiotics results in a broad antimicrobial spectrum effect. Another example is a combination of antiviral and antibacterial pharmaceutical ingredients, which results in the treatment of infection by unknown pathogens as well as viral infections often followed by bacterial infections. Another example is a combination of at least two pharmaceutically active ingredients that treat cancer or care for cancer symptoms, such as a combination of a topoisomerase inhibitor and an anti-cancer monoclonal antibody. Can be mentioned. Another example is the combination of an antibiotic and an antibiotic potentiator. Efficacy enhancing agents are enhanced and impart activity to pharmaceuticals, for example, pharmaceuticals such as antibiotics. Efficacy enhancers do not themselves have antimicrobial activity in combination with antibiotics such as eristomycin, chloramphenicol, tetracycline, linezolid, clindamycin or rifampin However, the potency enhancer enhances and significantly enhances the activity of the drug, in this case the antibiotic.

  Example 25: In another specific embodiment of the invention, the same pharmaceutically active ingredients are combined in at least two pharmaceutical formulations. Examples of the formulation include immediate release type or immediate action type and delayed release type or long acting type preparation. Delayed release or prolonged action is released over time, as described above, with beneficial effects including the ability to better treat or alleviate symptoms and reduce overall drug use. Capsule construction designs or drug formulation, excipients and tableting methods, and other means available to those skilled in the art can be achieved. Specific examples that are not intended to be limiting include: immediate acting / dissolving formulations that provide immediate action for urgent treatment and for maintenance Nitroglycerin with a slow-release formulation; Antibiotic with immediate-acting / fast-dissolving formulation for immediate increase in blood concentration and slow-release formulation; Immediate pain relief Treatment with pain medication combined with slow release and maintenance of treatment with pain medication; immediate dissolution or immediate action for immediate effect A non-limiting specific example of a sleep-improving agent, combined with a delayed release for sustained duration at night, includes Ambien.

  Example 26: In another specific embodiment of the invention, at least two anti-cholesterol pharmaceutical components, such as different types of statins, are combined in the combination drug therapy delivery system. Combination pharmacotherapy has many advantages because the effects of statins are very different.

  Example 27: In another specific embodiment of the present invention, two or more hypertensive combinations having a broad spectrum are included in the combination drug therapy delivery system. Contains the above antihypertensive drugs. It contains the same type of drug administration treatment, such as β-blockers or diuretics, or different types or classes of drug administration treatments, such as β-blockers and diuretics.

  Various other modifications can be made without departing from the spirit and scope of the invention. For example, the above-mentioned capsule is prepared by combining the various drugs described in the applicant's prior US Pat. Nos. 6,428,809 (Patent Document 1) and 6,702,683 (Patent Document 2) and the present application. US Patent Application No. 10 / 756,124 (patent document 3) and 10 / 479,438 (patent document 4) of US Patent Application No. 10 / 756,124 currently pending Can do. Also, other drug combinations, which may contain vitamins, dietary supplements, minerals, nutraceuticals, which may be combined with the capsules described above or prior to the applicant's prior patent. Or treatment with a combination to treat infectious diseases such as AIDS, TB and malaria, which may be used with the combination capsules, tablets or caplets described in pending patent applications, And treatment with combination drugs to care for pain, such as non-steroidal anti-inflammatory / proton pump inhibitors (NSAIDS / PPI). These are given as examples, but are not limiting in any way:

  Example 28. In another specific embodiment of the invention, at least two antimalarials are combined in the combination drug therapy delivery system. Specific examples of possible drug combinations include Artesunate and Mefloquine; Artemether and Lumefantrine; Chloroquine and Paracetamol. More generally, examples include at least two combinations of the following representative antimalarial drugs in the combination drug delivery system: artemator; lumefantrin; artesunate; amodiaquine HCl (Amodiaquine HCl); Atovaquone-proguanil; Quinine Sulfate; Chloroquine sulfate; Hydroxychloroquine Sulfate; Doxycycline; Mefloquine; Primaquine; Sulfadoxin (Sulfatexin) Sulfadoxine); Pyrimethamine; Paracetamol.

  Example 29. In another specific embodiment of the invention, at least two HIV therapeutic drug delivery means are combined in the combination drug therapy delivery system. Specific examples of possible drug combinations include drug administration treatment with at least two nucleoside reverse transcriptase inhibitors (NRTI). It includes, for example, Abacavir; lamivudine; didanosine; Emtricitabine; stavudine; tenofovir. Another example includes a combination of a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a nucleoside reverse transcriptase inhibitor (NRTI), for example, nevirapine (Nevirapine; NNRTI) and didanozine (NRTI); Efavirenz (NNRTI) and abacavir sulfate (NRTI). Another example is a combination of two NRTI's and one NNRTI, such as abacavir and lamivudine and efavirenz or abacavir and lamivudine and nevirapine. Yet another example is the combination of at least two 2 NRTI's and PPI: abacavir, lamivudine and lopinavir / ritonavir. Further examples include abacavir sulfate; didanodine; stavudine; tenofovir; disoproxil; fumarate; zidovudine; lamivudine; emtricitabine; lopinavir / ritonavir; nevirapine; efavirenz; Combining at least two of the anti-HIV drugs selected from the group. Still other combinations include a combination of AZT and 3TC; a combination of abacavir and AZT and 3TC; a combination of lopinavir and ritonavir; a combination of ABC and 3TC; and a combination of emtricitabine and tenofovir.

  Example 30: In another specific embodiment of the invention, at least two tuberculosis drug treatments are combined in the combination drug therapy delivery system. Specific examples of potential drug combinations include the combination of administering at least two of the following drugs: Isoniazid; Rifampicin; Pyrazinamide; Ethambutol HCl HCl); Streptomycin; Capreomycin; Cycloserine; Protionamide; Macrolides; Fluoroquinolones; p-Salicylic acid ).

  Example 31: In another specific embodiment of the invention, at least two pain medications are combined in the combination medication delivery system. Specific examples of possible drug combinations include the combination of administering at least two of the following drugs: Aspirin; Carbex; Codeine; Lubox; Merplan (Marplan); Nardil; Neurotin; OxyContin; Parnate; Topamax; Tylenol / Acetaminophen; Vicodein; Xyrem; Zarontin; Zoloft ; Zomig.

  Example 32. Another specific aspect of the present invention is to alleviate side effects of aspirin such as the effect of aspirin or acetylsalicylic acid combined in the combination drug delivery system on the acidity of aspirin. In combination with the active ingredient. Specific examples of potential drug combinations include a buffering compound or an acidic compound in combination with aspirin.

  Example 33. Another specific embodiment of the present invention includes a combination therapy for the treatment of lupus nephritis. Specific examples include a combination of methylprednisolone and cyclophosphamide.

  In addition, other modifications are allowed. For example, a preformed tablet, capsule or caplet containing one pharmaceutical ingredient can be obtained from the manufacturer. The pre-formed tablet can then be housed in the outer capsule filled with the second pharmaceutical ingredient by the pharmacist performing the formulation. This allows the pharmacist who is preparing to produce a package that combines custom drugs. Also, if desired, the present drug delivery system may have a notch in the vicinity of its center 26, so that the delivery system divides into two equally halved 28A, 28B The user can create tablets that are half dosed, each half of which will have equal amounts of both drugs to be dosed (see FIGS. 3A-3B) ).

  Various other modifications can be made without departing from the spirit and scope of the invention. For example, the core may contain a capsule containing a liquid or gel. Other modifications can also be made.

1 schematically illustrates a method of making a combination drug therapy delivery system in accordance with one specific embodiment of the present invention. Fig. 2 schematically illustrates a method of making a combination drug therapy delivery system according to a second specific embodiment of the present invention. Fig. 3 schematically illustrates how the combined drug therapy delivery system of Fig. 2 is divided or divided into two halved doses. 1 schematically illustrates a specific embodiment of a combination drug therapeutic delivery system capable of releasing a pharmaceutically active ingredient in time according to the present invention. 1 illustrates a specific embodiment of a combination drug delivery system.

Claims (27)

A pharmaceutical delivery package containing two or more different pharmaceutically active ingredients in a given unit dose, wherein the different pharmaceutical ingredients are (a) combined in a single delivery package and (b) Isolated from each other in a package, the package containing a core having a first pharmaceutically active ingredient, the core being at least partly by a capsule having a second pharmaceutically active ingredient A pharmaceutical delivery package characterized in that it is surrounded. The pharmaceutical delivery package of claim 1, wherein the capsule contains half of the capsule. The pharmaceutical delivery package of claim 1, wherein the capsule comprises a two-piece capsule. A first pharmaceutical ingredient contained in the core, a second pharmaceutical ingredient contained in one of the capsule pieces, and contained in the other of the capsule pieces. The pharmaceutical delivery package according to claim 3, further comprising a third pharmaceutical ingredient. 2. The pharmaceutical delivery package according to claim 1, wherein the core is coated with a barrier material. 6. A pharmaceutical delivery package according to claim 5, wherein the barrier material is preferably selected from the group consisting of gelatin, starch or cellulose materials. 7. The pharmaceutical delivery package of claim 6, wherein the cellulosic material includes hydroxypropyl methylcellulose. 4. The pharmaceutical delivery package of claim 3, wherein the capsule pieces are joined together by shrinking or press fitting. 2. The pharmaceutical delivery package of claim 1, wherein at least one of the two or more different pharmaceutical ingredients is in powder form, pellet form or bead form. The pharmaceutical delivery package according to claim 1, wherein at least one of the pharmaceutical ingredients is in a liquid form, a semi-liquid form or a gel form. The pharmaceutical delivery package of claim 1, wherein the capsule is coupled to the core. 4. The pharmaceutical delivery package of claim 3, wherein the capsule pieces are bonded together. 4. A pharmaceutical delivery package according to claim 3, wherein the capsule pieces are joined together by an abutment ring, a restraining ring-recess, or a restraining band. 4. A pharmaceutical delivery package according to claim 3, wherein the capsule pieces are joined together by applying a liquid in place. The capsule wall has physical properties selected from thickness, composition, solubility, and porosity, whereby the release of the pharmaceutically active ingredient contained therein to the digestive tract is controlled. The pharmaceutical delivery package according to claim 1, wherein: 16. A pharmaceutical delivery package according to claim 15, wherein the capsule wall is acid resistant or is permeable or soluble in a neutral to alkaline environment. The pharmaceutical delivery package of claim 1, wherein the core includes a capsule containing a liquid or gel. The pharmaceutical delivery package according to claim 1, wherein one of the pharmaceutical ingredients is selected from the group consisting of vitamins, dietary supplements, minerals and nutraceuticals. Antidiabetics and antihypertensives; antidiabetics and antihyperlipidemic agents,
Here, the antidiabetic agent is preferably selected from the group consisting of a sulfonylurea agent, a meglitinide agent, a biguanide agent, an insulin sensitivity improver and an α-glucosidase inhibitor, and the antihypertensive agent is preferably Is selected from the group consisting of ACE inhibitors, angiotensin II receptor antagonists, calcium antagonists, β-blockers and diuretics, or the antidiabetic agent is preferably a sulfonylurea agent, a meglitinide agent , A biguanide agent, an insulin sensitivity improving agent, and an α-glucosidase inhibitor, and the antihyperlipidemic agent is preferably a statin, fibrate, bile acid inhibitor, cholesterol absorption inhibitor And selected from the group consisting of niacin,
The pharmaceutical delivery package according to claim 1, comprising a combination of pharmaceutical ingredients selected from the group consisting of: One of the pharmaceutical components is a component that alleviates the side effects of other pharmaceutical components, a component that acts as a quencher for controlling the time with respect to the other pharmaceutical components, or the solubility and / or the other pharmaceutical components. Components that enhance absorbability, for example through controlling pH, or components that are fat-soluble and other pharmaceutical components contain fat or oil, or other pharmaceutical components Promotes absorption or bioavailability, or contains an enzyme-containing ingredient to alleviate the side effects of other pharmaceutical ingredients, or promotes absorption or inhibits absorption in selected parts of the digestive tract The pharmaceutical delivery package according to claim 1, wherein the pharmaceutical delivery package is selected from a component containing a surfactant or a component containing a sleep aid. The first and second pharmaceutical ingredients are effective in treating the same condition or disease, or the first and second pharmaceutical ingredients are both antibiotics, or the pharmaceutical ingredients One is an antiviral agent and the other medicinal component is an antibacterial agent, or one of the medicinal components is an antibiotic and the other medicinal component is an antibiotic potency enhancer, or the medicinal product One of the ingredients contains NRTI and the other medicinal ingredient contains NNRTI, or one of the medicinal ingredients contains PPI and the other medicinal ingredient contains NNRTI 2. The pharmaceutical delivery package according to claim 1, wherein one of the pharmaceutical ingredients contains NSAID and the other pharmaceutical ingredient contains PPI. The pharmaceutical delivery package according to claim 1, wherein the pharmaceutical component contains a drug for treating infection or pain. 23. A pharmaceutical delivery package according to claim 22, wherein the infectious disease comprises HIV / AIDS, TB or malaria. Enalapril maleate and its analogs and isomers and analogs and isomers of sympathetic beta-receptor blockers, methyldopa, nitrates, calcium blockers, hydralazine, prazosin or digoxin; metformin HCl and its analogs and isomers Antihyperglycemic drugs and angiotensin converting enzyme inhibitors (ACE inhibitors); Diabetes drugs and angiotensin II receptor antagonists such as losartan potassium and / or valsartan; Diabetes drugs and sympathetic nerves such as bisoprolol fumarate or metoprolol succinate β-receptor blockers; Diabetes and calcium channel blockers such as amlodipine or nifedipine; Diabetes and peripheral sympathetic receptor blockers such as prazosin hydrochloride; Diabetes and central adrenergic agonists such as methyldopa or clonidine Sex receptor stimulants; Meto Biguanides such as formin and sulfonylureas such as glipizide; biguanides such as metformin; thiazolidinediones such as rosiglitazone maleate; biguanides such as metformin; and α-glucosidase inhibitors such as cerivastatin; fast-acting oral insulin And sustained-release oral insulin; beta blockers, methyldopa, nitrate, calcium channel blockers, hydralazine, prazosin, digoxin combined, diabetic drugs and ACE inhibitors; diabetic drugs, ACE inhibitors, and beta blockers Medicine; Combination of diabetes drug, HMG-CoA reductase inhibitor such as simvastatin, atorvastatin or pravastatin and bile acid inhibitor such as colestipol hydrochloride; Diabetes drug, HMG-CoA reductase inhibitor and niacin compound; Diabetes drug HMG-CoA reductase inhibitor or A combination of a lipid-lowering drug such as gemfibrozil; a first pharmaceutical ingredient having side effects that cause constipation, nausea, gas / abdominal bloating, heartburn, pain or convulsions; A second pharmaceutical ingredient that relieves the side effects of the ingredient, for example, laxative treatment with drugs, treatment of nausea with drugs, anti-gas and anti-abdominal fullness treatment with drugs, acid suppression therapy with drugs, pain relief agents and A second medicinal component that is treated with a muscle relaxant; a pharmacological treatment for pain that causes constipation and nausea; a second component containing an oral narcotic and a stool softener and / or an anti-nausea component; immediate release Anti-cancer drugs such as methotrexate of the type and "quenchers" such as sustained-release L-leucovorin; a first pharmaceutical ingredient and a buffer to promote solubility and / or absorption of the first pharmaceutically active ingredient PH of agents A second pharmaceutical ingredient or substance that is optimally controlled or controlled; a first pharmaceutical ingredient that is soluble in fat and a second pharmaceutical ingredient or substance that contains fats and oils; a first pharmaceutical ingredient An enzyme, wherein the enzyme promotes absorbability and / or bioavailability of the pharmaceutically active ingredient or mitigates side effects; a first pharmaceutical ingredient and a nutraceutical or nexium (esomeprazole ) And vitamin B and other vitamins, antiviral pharmaceutical active ingredients and vitamin C or multivitamin supplements; pharmaceutical ingredients and absorption, or conversely, absorption, and inhibition of absorption in certain parts of the digestive tract Pharmaceutical ingredients and sleep-improving agents; infectious diseases, metabolic diseases, cardiovascular diseases, pain, cancer, transplantation-related treatments, gastrointestinal diseases, respiratory diseases, autoimmune diseases, vaccines The first and second components (multi-drug therapy) in the same class of medicines to treat or prevent the same symptoms or the same illness, such as; first and second antibiotics Anti-infective pharmaceutical active ingredient contained; Antiviral pharmaceutical ingredient and antibacterial pharmaceutical ingredient; Pharmaceutical active ingredient for treating cancer or caring for symptoms of cancer, for example, topoisomerase inhibitor, Cancer monoclonal antibody drugs; antibiotics and antibiotic efficacy enhancers; immediate action / dissolving preparations that provide immediate action for urgent treatment and slow release preparations for maintenance Immediate-release or immediate-action and delayed-release or long-acting formulations of the same drug, such as nitroglycerin And slowly Antibiotics with release agents; immediate action formulations to help relieve pain immediately; treatment with pain medications combined with slow release to maintain pain medication treatment; immediate A sleep-improving or immediate-acting formulation for the effect of the combination of a sleep-improving agent combined with a delayed release for sustained throughout the night, such as ambiene; of the combined drug therapy delivery system Two anti-cholesterol pharmaceutical ingredients such as different types of statins combined in; different drug treatments of the same type, such as beta-blockers or diuretics, or different, such as beta-blockers and diuretics Broad spectrum antihypertensive containing two or more antihypertensive drugs, including types or different classes of drug administration A combination of drugs; two or more antimalarial drugs such as artesunate and mefloquine; artemator and lumefantrin; chloroquine and paracetamol; and at least two of the following: artemator; lumefantrin; Artesunate; amodiaquine HCl; atovaquone-proguanil; quinine sulfate; chloroquine sulfate; hydroxychloroquine sulfate; doxycycline; mefloquine; primaquine; sulfadoxine; pyrimethamine; paracetamol; for example, abacavir; lamivudine; didanosine; Take at least two nucleoside reverse transcriptase inhibitors (NRTI), including tenofovir, non-nucleoside reverse transcriptase inhibitors (NNRTI) and nucleoside reverse transcriptase inhibitors (NRTI) such as nevirapine ( NNRTI) and didanodine (NRTI); efavirenz (NNRTI) and abacavir sulfate (NRTI); two NRTI's and one NNRTI, such as abacavir and lamivudine and efavirenz or abacavir and lamivudine and nevirapine; abacavir and lamivudine and lopinavir At least two NRTI's and PPI; at least two anti-HIV drugs selected from the group consisting of: abacavir sulfate; didanodine; stavudine; tenofovir; disoproxil; fumarate; zidovudine; lamivudine; emtricitabine; lopinavir / Ritonavir; nevirapine; efavirenz; nelfinavir; combination of AZT and 3TC; combination of abacavir and AZT and 3TC; combination of lopinavir and ritonavir; combination of ABC and 3TC; combination of emtricitabine and tenofovir; At least two tuberculosis Therapeutic medications: isoniazid; rifampicin; pyrazinamide; ethambrol HCl; streptomycin; capreomycin; cycloserine; prothionamide; macrolide antibiotics; fluoroquinolone antibiotics; and p-salicylic acid; at least two pain treatments selected from Dosage: Aspirin; Carbex; Codeine; Lubox; Merplan; Nardin; Neurotin; OxyContin; Parnate; Topamax; Tylenol / Acetaminophen; Baicodeine; Xyrem; Zarontin; Zoloft; and Zomig; Buffered in combination with aspirin A compound and / or an acid-acid compound; and containing two or more pharmaceutical ingredients selected from the group consisting of combination therapies for the treatment of lupus nephritis, such as methylprednisolone and cyclophosphamide thing Pharmaceutical delivery package according to claim 1, wherein. A pharmaceutical delivery package containing two or more different pharmaceutical ingredients in a given unit dose, wherein the different pharmaceutical ingredients are (a) combined in a single delivery package and ( b) isolated from each other within the package, and the package, when divided in half, will contain an equivalent amount of the pharmaceutical ingredient A pharmaceutical delivery package as described. A pharmaceutical delivery package containing two or more different pharmaceutical ingredients in a given unit dose, wherein the different pharmaceutical ingredients are (a) combined in a single delivery package and ( b) isolated from each other in the package and the following features:
(a) one of the pharmaceutical ingredients is selected from the group consisting of vitamins, dietary supplements, minerals and nutraceuticals;
(b) an antidiabetic agent and an antihypertensive agent; containing a combination of pharmaceutical ingredients selected from the group consisting of an antidiabetic agent and an antihyperlipidemic agent, wherein the antidiabetic agent is preferably Is selected from the group consisting of sulfonylureas, meglitinides, biguanides, insulin sensitizers and α-glucosidase inhibitors, and the antihypertensive agent is preferably an ACE inhibitor, angiotensin II receptor Preferably, the antidiabetic agent is selected from the group consisting of a body antagonist, a calcium antagonist, a β-blocker and a diuretic, or the antidiabetic agent is preferably a sulfonylurea agent, meglitinide agent, biguanide agent, insulin sensitivity improvement Selected from the group consisting of an agent and an α-glucosidase inhibitor, and the antihyperlipidemic agent is preferably a statin, fibrate, bile acid inhibitor Selected from the group consisting of drugs, cholesterol absorption inhibitors and niacin;
(c) one of the medicinal components alleviates the side effects of other medicinal components; or acts as a quencher to control time against other medicinal components; or the solubility and / or absorption of other medicinal components Promote, for example, by controlling pH; or fat-soluble and other pharmaceutical ingredients contain fat or oil; or absorption or bioavailability of other pharmaceutical ingredients Contains an enzyme to promote side effects or alleviate the side effects of other pharmaceutical ingredients; or a surfactant that promotes absorption or inhibits absorption in selected parts of the digestive tract Or is selected from ingredients containing sleep aids;
(d) the first and second pharmaceutical ingredients are effective in treating the same condition or disease; or the first and second pharmaceutical ingredients are both antibiotics; or One of the medicinal components is an antiviral agent and the other medicinal component is an antibacterial agent; or one of the medicinal components is an antibiotic and the other medicinal component is an antibiotic efficacy enhancer; or One of the medicinal ingredients contains NRTI and the other medicinal ingredient contains NNRTI; or one of the medicinal ingredients contains PPI and the other medicinal ingredient contains NNRTI Or one of the medicinal ingredients contains NSAID and the other medicinal ingredient contains PPI;
(e) the medicinal component contains a drug for treating infection or pain;
(f) the infection includes HIV / AIDS, TB or malaria; and
(g) Enalapril maleate and its analogs and isomers, and analogs and isomers of sympathetic beta-receptor blockers, methyldopa, nitrate, calcium blockers, hydralazine, prazosin or digoxin; metformin HCl and its analogs And angiotensin converting enzyme inhibitors (ACE inhibitors); diabetic drugs and angiotensin II receptor antagonists such as losartan potassium and / or valsartan; diabetic drugs and bisoprolol fumarate or metoprolol succinate Sympathetic beta-receptor blockers; diabetes drugs and calcium channel blockers such as amlodipine or nifedipine; diabetes drugs and peripheral sympathetic receptor blockers such as prazosin hydrochloride; diabetes drugs and central centers such as methyldopa or clonidine Sex adrenergic receptor stimulants; Biguanides such as toformin and sulfonylureas such as glipizide; biguanides such as metformin; thiazolidinediones such as rosiglitazone maleate; biguanides such as metformin; alpha-glucosidase inhibitors such as cerivastatin; fast-acting oral insulin And sustained release oral insulin; beta blockers, methyldopanilate, calcium channel blockers, hydralazine, prazosin, digoxin combined, diabetics and ACE inhibitors; diabetics, ACE inhibitors, and beta blockers A combination of a diabetic drug and an HMG-CoA reductase inhibitor such as simvastatin, atorvastatin or pravastatin and a bile acid inhibitor such as colestipol hydrochloride; a diabetic drug and an HMG-CoA reductase inhibitor and a niacin compound; , HMG-CoA reductase inhibitor or A combination of a lipid-lowering drug such as gemfibrozil; a first pharmaceutical ingredient having side effects that cause constipation, nausea, gas / abdominal bloating, heartburn, pain or convulsions; A second pharmaceutical ingredient that relieves the side effects of the ingredient, for example, laxative treatment with drugs, treatment of nausea with drugs, anti-gas and anti-abdominal fullness treatment with drugs, acid suppression therapy with drugs, pain relief agents and A second medicinal component that is treated with a muscle relaxant; a pharmacological treatment for pain that causes constipation and nausea; a second component containing an oral narcotic and a stool softener and / or an anti-nausea component; immediate release Anti-cancer drugs such as methotrexate of the type and "quenchers" such as sustained-release L-leucovorin; a first pharmaceutical ingredient and a buffer to promote solubility and / or absorption of the first pharmaceutically active ingredient P A second pharmaceutical ingredient or substance that optimizes or controls H; a first pharmaceutical ingredient that is soluble in fat; a second pharmaceutical ingredient or substance that contains fat; and a first pharmaceutical ingredient; An enzyme, wherein the enzyme promotes absorbability and / or bioavailability of the pharmaceutically active ingredient or mitigates side effects; first pharmaceutical ingredient and nutraceutical or nexium (esomeprazole) Vitamins such as vitamin B and vitamins, antiviral active pharmaceutical ingredients and vitamin C or multivitamin supplements; pharmaceutical ingredients and promote absorption, or conversely, inhibit absorption in certain areas of the digestive tract Surfactants; pharmaceutical ingredients and sleep-improving agents; infectious diseases, metabolic diseases, cardiovascular diseases, pain, cancer, transplantation-related treatments, gastrointestinal diseases, respiratory diseases, autoimmune diseases, vaccines, etc. First and second components (multi-drug therapy) in the same class of medicines to treat or prevent the same symptoms and diseases; contains first and second antibiotics Active anti-infective pharmaceutical active ingredients; antiviral and antimicrobial pharmaceutical ingredients; active pharmaceutical ingredients for treating cancer or caring for symptoms of cancer, such as topoisomerase inhibitors and anti-cancer Monoclonal antibody drugs; antibiotics and antibiotic efficacy enhancers; with immediate / dissolving formulations that provide immediate action for urgent treatment and with slow-release preparations for maintenance Immediate-release or immediate-action and delayed-release or long-acting formulations of the same drug, such as nitroglycerin Release slowly Antibiotics with immediate release; immediate action preparations to help relieve pain immediately; treatment with pain medication combined with slow release to maintain pain medication treatment; immediate A sleep-improving or immediate-acting formulation for the effect of the combination of a sleep-improving agent combined with a delayed release for sustained throughout the night, such as ambiene; of the combined drug therapy delivery system Two anti-cholesterol pharmaceutical ingredients such as different types of statins combined in; different drug treatments of the same type, such as beta-blockers or diuretics, or different, such as beta-blockers and diuretics A broad spectrum antihypertensive drug containing two or more antihypertensive drugs, including types or treatments of different classes of drugs Combinations; two or more antimalarial drugs such as artesunate and mefloquine; artemator and lumefantrin; chloroquine and paracetamol; and at least two of the following: artemator; lumefantrin; artesunate Amodiaquine HCl; atovaquone-proguanil; quinine sulfate; chloroquine sulfate; hydroxychloroquine sulfate; doxycycline; mefloquine; primaquine; sulfadoxine; pyrimethamine; paracetamol; for example, abacavir; lamivudine; Contains at least two nucleoside reverse transcriptase inhibitors (NRTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a nucleoside reverse transcriptase inhibitor (NRTI), such as nevirapine (NNRTI) And danavidin (NRTI); efavirenz (NNRTI) and abacavir sulfate (NRTI); two NRTI's and one NNRTI, such as abacavir and lamivudine and efavirenz or abacavir and lamivudine and nevirapine; abacavir and lamivudine and lopinavir / ritonavir At least two NRTI's and PPI; at least two anti-HIV drugs selected from the group consisting of: abacavir sulfate; didanodine; stavudine; tenofovir; disoproxil; fumarate; zidovudine; lamivudine; emtricitabine; lopinavir / ritonavir Nevirapine; efavirenz; and nelfinavir; combination of AZT and 3TC; combination of abacavir and AZT and 3TC; combination of lopinavir and ritonavir; combination of ABC and 3TC; combination of emtricitabine and tenofovir; At least two tuberculosis treatments Dosage for: isoniazid; rifampicin; pyrazinamide; ethambrol HCl; streptomycin; capreomycin; cycloserine; prothionamide; macrolide antibiotics; fluoroquinolone antibiotics; and p-salicylic acid; for at least two pain treatments selected from Dosage: Aspirin; Carbex; Codeine; Lubox; Merplan; Nardil; Neurotin; OxyContin; Parnate; Topamax; Tylenol / Acetaminophen; Baicodeine; Xyrem; Zarontin; Zoloft; and Zomig; A buffering compound in combination with aspirin And / or an acidic compound; and containing two or more pharmaceutical ingredients selected from the group consisting of combination therapies for the treatment of lupus nephritis, such as methylprednisolone and cyclophosphamide One Pharmaceutical delivery package, characterized in that others are those characterized with at more. A pharmaceutical delivery package containing two or more different pharmaceutical ingredients in a given unit dose, wherein the different pharmaceutical ingredients are (a) combined in a single delivery package and (b) 27. Isolated from one another in the package, wherein the package, when divided in half, will contain an equivalent amount of the pharmaceutical ingredient. Pharmaceutical delivery package.

Images