MXPA04003927A - An albuterol and ipratropium inhalation solution, system, kit and method for relieving symptoms of chronic obstructive pulmonary disease. - Google Patents

Abstract

The present invention relates to a dual bronchodilator inhalation solution, system, kit and method for relieving bronchospasm in patients suffering from chronic obstructive pulmonary disease (COPD). In one alternative embodiment, the solution of the present invention is a prepackaged, sterile, premixed, premeasured single unit dose of albuterol and ipratropium bromide for patients suffering from COPD. The present solution may be free of antimicrobial preservatives, such as benzalkonium chloride. In another alternative embodiment, the solution of the present invention comprises about 2.50 mg albuterol and about 0.50 mg ipratropium bromide.

Description

A SOLUTION OF INHALATION OF ALBUTEROL AND IPRATROPIO, SYSTEM, EQUIPMENT AND METHOD TO ALLEVIATE THE SYMPTOMS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE CROSS REFERENCE WITH RELATED REQUESTS This application is a continuation in part of the U.S. Patent Application. Serial No. 10 / 034,657, filed on December 28, 2001, which claims priority under the U.S.C. 35 §1 19 (e) of the Patent Application of E.U.A. provisional No. 60 / 346,078 filed on October 26, 2001. The description of all of these prior applications is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION The present invention relates to a combination bronchodilator therapy to alleviate symptoms associated with chronic obstructive pulmonary disease.

BACKGROUND OF THE INVENTION Chronic obstructive pulmonary disease (COPD) is a slow, progressive disease in the airways that causes a decline in lung function that is not reversible in its entirety. The limitation of the respiratory tract in COPD is associated with an irregular inflammatory response of the lungs in poisonous particles or gases. In the United States, an estimated 16 million Americans have been diagnosed with some form of COPD, and another 16 million have the condition but have not yet been diagnosed. According to the Centers for Control and Prevention in the United States, COPD is the fourth leading cause of death in the United States, (after heart disease, cancer and heart attacks), claiming the lives of 12,000 Americans annually. In terms of use for health care, the number of physician visits to attend COPD in the United States has increased from 9.3 million to 16 million between 1985 and 1995. The number of hospitalizations for COPD in 1995 was estimated at 500,000. Although they are maintained, rates of hospitalization and death due to COPD are higher in men than in women, death rates increase more rapidly in women in recent years. COPD is clearly a significant and growing threat to health care in the United States and in the rest of the world. In the prior art, antibacterial agents such as benzalkonium chloride (BAC) are often present in inhalation solutions used to treat COPD. The presence of BAC in these solutions generally does not affect the response to the bronchodilator in the short term (single dose). However, the reported cases suggest that repeated use of COPD treatments with BAC may result in paradoxical bronchoconstriction. When inhaled by subjects with COPD, BAC can also produce dose-dependent bronchoconstriction. Regardless of these side aspects, many commercially available inhalation solutions contain BAC. Also, treatments for COPD are often presented in multiple dose units and must be diluted to specific concentrations suitable to treat patients. This presents several problems. For example, COPD treatments require the administration of a single dose unit from multiple dosage units, which sometimes lack the appropriate mixture or dilution instructions, or the instructions for preparing and using the COPD treatment may be difficult to follow or you can easily lose. With a higher level of importance is the dilution or casual mixing of the COPD medications, which can result in the administration of wrong doses. This can be especially harmful for patients with less tolerance to higher doses of asthma medications. Incorrect mixing can also result in treatment failures, thereby increasing the time, expenses and costs for medical personnel associated with the therapy. Accordingly, there is a need for an improved solution, systems, equipment and inhalation methods to alleviate the symptoms associated with COPD.

BRIEF DESCRIPTION OF THE INVENTION An object of the present invention is to provide a double bronchodilator inhalation solution for relieving bronchospasm in patients suffering from COPD. Another object of the present invention is to provide a previously measured, pre-packaged, sterilized, previously mixed albuterol and ipratropium inhalation solution previously measured for the relief of bronchospasm in patients suffering from COPD. It is still another object of the present invention to provide a BAC-free albuterol and ipratropium inhalation solution for treating broncho-spasm associated with COPD.

A further object of the present invention is to provide a method for administering an inhalation formulation of albuterol and ipratropium for the relief of broncho-spasm associated with COPD. A further object of the present invention is to provide an equipment and / or system for administering a double bronchodilator to alleviate the bronchospasm associated with COPD. A further object of the present invention is to provide a method for making an inhalation solution of albuterol and ipratropium to be used in the relief of broncho-spasm associated with COPD. Another object of the present invention includes a device to be used in the relief of COPD symptoms. Other objects, features and advantages of the present invention will be apparent to those ordinarily skilled in the art in view of the following detailed description of the present invention and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS Figures 1 to 4 illustrate a non-limiting example for administering the inhalation solution of the present invention by means of a nebulizer.

Figure 5 illustrates a non-limiting example of a previously packaged unified equipment or system of the present invention. Figure 6 illustrates a non-limiting example of one or more pre-filled containers comprising an inhalation system of the present invention. Figure 7 illustrates a non-limiting example of a label used in the present invention. Figure 8 shows the average change in FEV-? , measured on day 14.

DETAILED DESCRIPTION OF THE INVENTION Albuterol The present invention is based on the bronchodilating effects of albuterol to provide relief of symptoms associated with COPD. As used in the present description, the term "albuterol" includes, but is not limited to, any form of albuterol, which has the ability to produce a desired bronchodilation effect in patients, including, but not limited to, all tautomeric forms, enantiomeric forms, stereoisomers, anhydrides, acid addition salts, base salts, soluble-solvent compounds, analogs and albuterol derivatives. In the present invention, acceptable salts of albuterol may include, but are not limited to, hydrochloride, sulfate, maleate, tartrate, citrate, and the like. These salts are described in the patent of E.U.A. No. 3,644,353, which is incorporated herein by reference in its entirety. In the present invention, the preferred albuterol salt is sulfate. In an alternative embodiment, the inhalation solution of the present invention comprises the sulfate salt of the racemic albuterol. Albuterol sulfate is a relatively selective beta-2-adrenergic bronchodilator with an empirical formula C13H21 NO3. The chemical name for albuterol sulfate is sulfate of - [(tert-butylamino) methyl] -4-hydroxy-m-xylene-, '-dol (2: 1) (salt), and its chemical structure is established as follows: Ipratropium The present invention is also based on the bronchodilation effect of ipratropium to provide relief of symptoms associated with COPD. Ipratropium is an anticholinergic bronchodilator. As used in the present description, the term "ipratropium" includes, but is not limited to, any form of ipratropium, which has the ability to produce a desired bronchodilation effect in patients suffering from COPD, which includes, but is not limited to, all tautomeric forms, enatiomeric forms, stereoisomers, anhydrides , acid addition salts, base salts, soluble-solvent compounds, analogs and derivatives of ipratropium. In the present invention, acceptable salts of ipratropium may include, but are not limited to, halide salts such as bromide, chloride and iodide. These and other acceptable salts are described in the U.S. Patent. No. 3,505,337, which is incorporated in its entirety to the present description as a reference. In one embodiment of the present invention, the preferred salt of ipratropium is bromide, which is described chemically as 8-azomiabicyclo [3.2.1] -octane bromide, 3- (3, hydroxyl-1 -oxo-2-phenylpropoxy) -8-methyl-8- (1-methylethyl), monohydrate, (endo, sin) -, (±) -, ipratropium bromide has a molecular weight of 430.4 and an empirical formula 02 ?? 3 ?? G 03 ·? 20. This is freely soluble in water and lower alcohol, and is insoluble in lipophilic solvents, such as ether, chloroform and fluorocarbon. The established chemical structure of ipratropium bromide is as follows: In the present invention, albuterol and ipratropium can be provided in a variety of pharmaceutically acceptable carriers, including, but not limited to, water or other aqueous solutions comprising a pharmaceutically acceptable amount of an osmotic agent. In an alternative embodiment, the inhalation solution of the present invention comprises a therapeutically effective amount of albuterol and ipratropium. As used in the present description, the phrase "therapeutically effective amount of albuterol and / or ipratropium" means a safe and tolerable amount of both compounds, as a basis in industry standards and / or regulatory standards. Said amount is sufficient to effectively induce bronchodilation and / or provide relief of bronchospasm in patients suffering from COPD. In the inhalation solution of the present invention, a therapeutically effective amount of albuterol may include from about 0.63 mg to about 4.2 mg of albuterol. In this case, the potency of albuterol is equivalent to from about 0.75 mg to about 5 mg of albuterol sulfate. In an alternative embodiment, a therapeutically effective amount of albuterol may include about 2.5 mg of albuterol. In another alternative embodiment of the present invention, a therapeutically effective amount of albuterol may include from about 0.60 mg to about 5.0 mg of albuterol, including the following intermediate ranges of albuterol: from about 0.60 mg to about 0.70 mg; from about 0.71 to about 0.80 mg; from about 0.81 mg to about 0.90 mg; from about 0.91 mg to about 1.00 mg; from about 1.0 mg to about 1.0 mg; from about 1.1 mg to about 1.0 mg; from about 1.21 mg to about 1.30 mg; from about 1.31 mg to about 1.40 mg; from about 1.41 mg to about 1.50 mg; from about 1.51 mg to about 1.60 mg; from about 1.61 mg to about 1.70 mg; from about 1.71 mg to about 1.80 mg; from about 1.81 mg to about 1.90 mg; from about 1.91 mg to about 2.00 mg; from about 2.01 mg to about 2.10 mg; from about 2.1 mg to about 2.20 mg; from about 2.21 mg to about 2.30 mg; from about 2.31 mg to about 2.40 mg; from about 2.41 mg to about 2.50 mg; from about 2.51 mg to about 2.60 mg; from about 2.61 mg to about 2.70 mg; from about 2.71 mg to about 2.80 mg; from about 2.81 mg to about 2.90 mg; from about 2.91 mg to about 3.00 mg; from about 3.01 mg to about 3.10 mg; from about 3.1 mg to about 3.20 mg; from about 3.21 mg to about 3.30 mg; from about 3.31 mg to about 3.40 mg; from about 3.41 mg to about 3.50 mg; from about 3.51 mg to about 3.60 mg; from about 3.61 mg to about 3.70 mg; from about 3.71 mg to about 3.80 mg; from about 3.81 mg to about 3.90 mg; from about 3.91 mg to about 4.00 mg; from about 4.01 mg to about 4.10 mg; from about 4.1 mg to about 4.20 mg; from about 4.21 mg to about 4.30 mg; from about 4.31 mg to about 4.40 mg; from about 4.41 mg to about 4.50 mg; from about 4.51 mg to about 4.60 mg; from about 4.61 mg to about 4.70 mg; from about 4.71 mg to about 4.80 mg; from about 4.81 mg to about 4.90 mg; from about 4.91 mg to about 5.00 mg.

In another alternative embodiment of the present invention, a therapeutically effective amount of albuterol may include from about 0.75 mg to about 5.0 mg albuterol sulfate, including the following intermediate amounts: from about 0.75 mg to about 0.80 mg; from about 0.81 mg to about 0.90 mg; from about 0.91 mg to about 1.00 mg; from about 1.0 mg to about 1.0 mg; from about 1.1 mg to about 1.0 mg; from about 1.2 mg to about 1.30 mg; from about 1.31 mg to about 1.40 mg; from about 1.41 mg to about 1.50 mg; from about 1.51 mg to about 1.6 mg; from about 1.61 mg to about 1.70 mg; from about 1.71 mg to about 1.80 mg; from about 1.81 mg to about 1.90 mg; from about 1.91 mg to about 2.00 mg; from about 2.01 mg to about 2.10 mg; from about 2.1 mg to about 2.20 mg; from about 2.21 mg to about 2.30 mg; from about 2.31 mg to about 2.40 mg; from about 2.41 mg to about 2.50 mg; from about 2.51 mg to about 2.60 mg; from about 2.61 mg to about 2.70 mg; from about 2.71 mg to about 2.80 mg; from about 2.81 mg to about 2.90 mg; from about 2.91 mg to about 3.00 mg; from about 3.01 mg to about 3.10 mg; from about 3.1 mg to about 3.20 mg; from about 3.21 mg to about 3.30 mg; from about 3.31 mg to about 3.40 mg; from about 3.41 mg to about 3.50 mg; from about 3.51 mg to about 3.60 mg; from about 3.61 mg to about 3.70 mg; from about 3.71 mg to about 3.80 mg; from about 3.81 mg to about 3.90 mg; from about 3.91 mg to about 4.00 mg; from about 4.01 mg to about 4.10 mg; from about 4.1 mg to about 4.20 mg; from about 4.21 mg to about 4.30 mg; from about 4.31 mg to about 4.40 mg; from about 4.41 mg to about 4.50 mg; from about 4.51 mg to about 4.60 mg; from about 4.61 mg to about 4.70 mg; from about 4.71 mg to about 4.80 mg; from about 4.81 mg to about 4.90 mg; from about 4.91 mg to about 5.00 mg. In another alternative embodiment of the present invention, a therapeutically effective amount of albuterol may include from about 0.020% to about 0.14% by weight of albuterol, including the following intermediate ranges: from about 0.020% by weight to about 0.029% by weight; from about 0.030% by weight to about 0.039% by weight; from about 0.040% by weight to about 0.049% by weight; from about 0.050% by weight to about 0.059% by weight; from about 0.060% by weight to about 0.069% by weight; from about 0.070% by weight to about 0.079% by weight; from about 0.080% by weight to about 0.089% by weight; from about 0.090% by weight to about 0.099% by weight; from about 0.10% by weight to about 0.14% by weight. In yet another alternative embodiment of the present invention, a therapeutically effective amount of albuterol may include from about 0.025% to about 0.17% by weight of albuterol sulfate, including the following intermediate ranges: from about 0.025% by weight to about 0.029% by weight weight; from about 0.030% by weight to about 0.039% by weight; from about 0.040% by weight to about 0.049% by weight; from about 0.050% by weight to about 0.059% by weight; from about 0.060% by weight to about 0.069% by weight; from about 0.070% by weight to about 0.079% by weight; from about 0.080% by weight to about 0.089% by weight; from about 0.090% by weight to about 0.099% by weight; from about 0.10% by weight to about 0.17% by weight. In another alternative embodiment of the present invention, a therapeutically effective amount of ipratropium bromide can include from about 0.01 mg to about 1.0 mg of ipratropium bromide. Said therapeutically effective amount may also include the following intermediate ranges of ipratropium bromide: from about 0.01 mg to about 0.02 mg; from about 0.02 mg to about 0.04 mg; from about 0.05 mg to about 0.07 mg; from about 0.08 mg to about 0.10 mg; from about 0.1 mg to about 0.13 mg; from about 0.14 mg to about 0.16 mg; from about 0.17 mg to about 0.19 mg; from about 0.20 mg to about 0.22 mg; from about 0.23 mg to about 0.25 mg; from about 0.26 mg to about 0.28 mg; from about 0.29 mg to about 0.31 mg; from about 0.32 mg to about 0.34 mg; from about 0.35 mg to about 0.37 mg; from about 0.36 mg to about 0.38 mg; from about 0.39 mg to about 0.41 mg; from about 0.42 mg to about 0.44 mg; from about 0.45 mg to about 0.47 mg; from about 0.48 mg to about 0.50 mg; from about 0.51 mg to about 0.53 mg; from about 0.54 mg to about 0.56 mg; from about 0.57 mg to about 0.59 mg; from about 0.60 mg to about 0.62 mg; from about 0.63 mg to about 0.65 mg; from about 0.66 mg to about 0.68 mg; from about 0.69 mg to about 0.71 mg; from about 0.72 mg to about 0.74 mg; from about 0.75 mg to about 0.77 mg; from about 0.79 mg to about 0.81 mg; from about 0.82 mg to about 0.84 mg; from about 0.85 mg to about 0.87 mg; from about 0.88 mg to about 0.91 mg; from about 0.92 mg to about 0.94 mg; from about 0.95 mg to about 0.97 mg; from about 0.98 mg to about 1.00 mg. In another alternative embodiment of the present invention, a therapeutically effective amount of ipratropium may include from about 0.001% to about 0.030% weight percent ipratropium bromide, including the following intermediate ranges of ipratropium bromide: from about 0.001% by weight to about 0.005% by weight; from about 0.006% by weight to about 0.010% by weight; from about 0.01 1% by weight to about 0.015% by weight; from about 0.016% by weight to about 0.020% by weight; from about 0.021% by weight to about 0.025% by weight; 0.026% by weight up to about 0.030% by weight. Most pharmaceutical inhalation solutions contain the antibacterial agent BAC. One problem with these solutions is that BAC can produce paradoxical bronchoconstriction if the solution is administered repeatedly for short intervals. Another problem is thatWhen inhaled by patients, BAC can produce dose-dependent bronchoconstriction. The inhalation solution of the present invention can be provided free of BAC, thereby making it suitable, especially in an emergency situation, wherein the inhalation solution is administered repeatedly for a short period of time. Also, the administration of a BAC-free inhalation solution to a patient reduces the concomitant responsibility or adverse effects associated with the BAC. This also reduces the toxicity and other side effects associated with BAC.

The inhalation solution of the present invention, also can be provided sterilized, in unit dose treatments, thus eliminating the need to include the BAC in the solution.

In addition, as shown in Table 1, in its sterilized form, the formulation of the present invention (which comprises an amount therapeutically effective of albuterol sulfate and ipratropium bromide) provides a stable inhalation solution, such that the Formulation can be stored (for example, on a shelf) for long periods of time.

TABLE 1 Stability data as percentage per tag requirement (0.083 wt.% of Ibuterol sulfate and 0.017 wt.% of iprotropium bromide) As established, the compositions provided in the present disclosure are stable For example, the compositions provided in the present disclosure are stored at temperatures between about 15 ° C and about 30 ° C, and remain stable for a relatively long period of time In one embodiment, the compositions are stored at a temperature of 25 ° C. of the compositions provided in the present disclosure may contain more than 80%, 95%, 90% or 95% of the initial amount of the active ingredient, for example, albuterol and ipratropium at a certain temperature for a long period of time. , for example, a composition that is stable for 30 days at a temperature of 25 ° C, could have more than 80%, 85%, 90% or 95% of the Initial ntidad of the active ingredients present in the composition at 30 days followed by a storage at a temperature of 25 ° C. In another embodiment, the heroin compositions are stable during long-term storage, wherein the compositions are suitable for administration to a subject in need thereof when they have been stored for a period of time (i.e., shelf life) during a period greater than 1, 2 or 3 years at a temperature of 25 ° C. In other embodiments of the present disclosure, using the Arrhenius kinetics, > 80% or > 85% or > 90% or > 95% it is estimated that, for example, the bronchodilating agent remains after said storage. Other indications of the stability of the present compositions can be shown in terms of by-products or degradation products over time, as shown in Tables 2 and 3, which are found below.

TABLE 2 ND = Not detected TABLE 3 In one embodiment, the compositions of the present disclosure are at least substantially clear, based on the color measurement tests established by the America Public Health Association ("APHA"). In another embodiment of the present invention, the APHA color results are maintained for the compositions of the present disclosure up to 24 months at a temperature of 25 ° C within the range from 0 to 5 units (in most cases 0 units) ), based on the APHA standards. In one embodiment, the process of the present invention provides compositions having an albuterol content of from about 2.5 mg to about 2.75 mg per vial. In another alternative embodiment, the process of the present invention provides compositions having an ipratropium content from about 0.45 to 0.55 mg per bottle. In yet another alternative embodiment, the process of the present invention provides an average fill volume from about 2.84 to about 3.30 ml inside each bottle. In another alternative embodiment, the compositions of the present invention may contain minimal amounts of contaminants including, but not limited to, the following: TABLE 4 In another alternative embodiment, the compositions of the present invention may contain minimal amounts of subject particle, including but not limited to the following: NMT from about 1000 to 5000, preferably from about 3800 particles / flask > 20m; NMT from about 10 to 100, preferably about 80 particles / flask > 10Om; or NMT of about 1 to 5, preferably about 3 particles / flask > 25F ?? Another benefit of a sterilized inhalation solution is that it reduces the possibility of introducing contaminants into a patient when administered, therefore, the possibility of an opportunistic infection in the patient is reduced. Non-adherence to COPD medication therapy and medication errors are considerable problems. These problems can be significantly reduced by providing COPD patients with a previously packaged, previously mixed and previously measured amount of aibuterol and ipratropium. These compounds are provided in the manner that is done with simple COPD therapy because they increase convenience and eliminate confusion in the preparation of adequate doses. These advantages are especially significant in cases where treatments are presented in multiple dose units and must be diluted to specific concentrations suitable for the treatment of patients. As stated previously, they have various problems. The present invention overcomes the aforementioned problems by providing therapeutically effective amounts of both aibuterol and ipratropium in unit of pre-packaged doses, previously mixed, previously measured and / or in units of doses. In one embodiment, the present invention comprises one or more containers previously filled. Said one or more containers each comprise a single dose unit of an aqueous solution comprising a therapeutically effective amount of albuterol and ipratropium for the treatment of COPD. Providing the inhalation solution in this way eliminates the need to dilute or mix the COPD medications to obtain the appropriate doses for the treatment. Also, no special pharmaceutical compounds are required, therefore the possibility of medication errors is reduced. Additionally, there is a lower risk of cross-contamination, and less waste of medication when an inhalation solution is provided in a pre-mixed form ready for use. Other features of the present invention include improving user compliance and quality of life compared to conventional treatments for COPD. While the compliance level of any COPD treatment depends in part on the user's motivation and the ability of the individual administering the treatment, compliance can nonetheless be improved by controlling factors such as the ease with which it can be administered. the treatment, as well as the convenience of receiving the treatment. The present invention provides a convenient, fast and reliable treatment for COPD and clearly represents an improvement over traditional COPD treatments. The present invention is also designed to facilitate user compliance by providing one or more dispensing containers comprising a previously measured, pre-mixed inhalation solution comprising a single dose unit of a therapeutically effective amount of albuterol and iprotropium for the treatment of COPD. . Said containers can be used in a method for the treatment of COPD or the containers can be incorporated into a system and / or equipment to treat it. In an alternative embodiment, the present invention is a sterilized inhalation solution, previously mixed, previously measured, BAC-free comprising a single dose unit of a therapeutically effective amount of albuterol and ipratropium in a single container. Each dose unit container comprises 3.0 mg / 3 ml of albuterol sulfate (equivalent to 2.5 mg of albuterol) and 0.5 mg of ipratropium bromide in a sterile aqueous solution. Sodium chloride can be added to make the isotonic solution and hydrochloric acid can be added to adjust the pH of the solution at about 4.0. The inhalation solution of the present invention may or may not include a chelating agent, such as EDTA. In another alternative embodiment, the inhalation solution of the present invention can be supplied as 3 ml of nebulizer solution, sterilized, BAC free comprising from about 0.20 to about 0.5 mg of ipratropium bromide and from about 0.75 mg / 3 my up to approximately 3.0 mg / 3 ml of albuterol sulfate. The nebulizer solution is contained in a low density polyethylene (LDPE) container of dosage unit.

Each dose unit container can be arranged in a bag of Aluminum foil, and each foil pouch can hold 5 or more dose unit containers. Each aluminum foil bag containing the dose unit container can be placed on a base of paperboard.

The present invention provides an inhalation solution of albuterol and ipratropium to treat various stages of COPD, including but not limited to stages 0 to III. Some characteristics associated with Various stages of COPD are shown in Table 5. The information in this table is presented for illustrative purposes only. This does not have the intention to limit the scope of the present invention.

TABLE 5 Stage Severity Description 0 At risk • Normal spirometry • Chronic symptoms (cough, sputum production) I Media FEWFVC < 70% • FEV-, > 80% expected • With or without chronic symptoms II Moderate FEWFVC < 70% 30% > FEVi < 80% expected • With or without chronic symptoms III Severe FEVi / FVC < 70% • FEV-i < 30% expected or less than 50% expected with respiratory failure or clinical signs of failure of the right side of the heart.

In the present invention, a therapeutically effective amount of albuterol and ipratropium is administered to induce bronchodilation and / or provide relief of bronchospasm associated with COPD. Said amount of albuterol and ipratropium can be administered to a patient after the onset of bronchospasm to reduce aspiration difficulties resulting from COPD. In another embodiment, albuterol and ipratropium can be administered prophylactically, that is, to prevent the progression of COPD. The amount of albuterol and ipratropium that will be administered will be determined on an individual basis and will be based at least partially on the consideration of the size of the patient, the severity of the symptoms to be treated and the intended results. The current dose (amount of albuterol and ipratropium administered at that time) and the number of administrations per day will depend on the form of administration, such as inhaler, nebulizer or oral administration. For example, about 2.5 mg of albuterol and about 0.5 mg of ipratropium bromide administered by nebulization 4 times a day with up to 2 additional doses of 3 ml allowed per day, if necessary, would be adequate to produce the desired bronchodilation effect in the majority of patients. In addition, the albuterol and ipratropium inhalation solution of the present invention can be administered together with one or more other drugs. For example, an antiasthmatic drug such as theophylline or terbutaline, or an antihistamine or analgesic such as aspirin, acetaminophen or ibuprofen, may be administered with or in the temporary proximity of the dose for the administration of a therapeutically effective amount of albuterol. The present invention and the one or more drugs can be administered in a formulation or in the form of two separate entities. In accordance with the present invention, a therapeutically effective amount of albuterol and ipratropium, alone or in combination with another drug (s), may be administered periodically as necessary to reduce the symptoms of COPD. In another alternative embodiment, the inhalation solution of the present invention can be administered by a nebulizer. Such a nebulizer includes, but is not limited to, a pressure nebulizer, an ultrasonic nebulizer, and an aspiration activated nebulizer. Preferably, the nebulizer is a pressure nebulizer connected to an air compressor with a suitable air flow. The nebulizer is equipped with a suitable mouthpiece or mask. Specifically, a Pari-LC-Plus ™ nebulizer (with mask or nozzle) connected to a PRONEB ™ compressor can be used to deliver the inhalation solution of the present invention to a patient. In an alternative modality, the system and / or equipment of the present invention comprises an inhalation solution comprising a therapeutically effective amount of albuterol and ipratropium in a pre-packaged, pre-mixed dosage form and / or a single dose unit form for the treatment of COPD. The inhalation solution can be sterilized and / or BAC-free. In another embodiment, the present invention provides a system and / or equipment for organizing and storing one or more pre-filled distribution containers, wherein each container comprises a pre-mixed inhalation solution, previously measured. The inhalation solution comprises a single dose unit of a therapeutically effective amount of albuterol and ipratropium. Said system and / or equipment can provide said containers in a pre-packaged form. The one or more containers may be comprised of plastic including, but not limited to, semi-permeable plastic, such as LDPE. The container may also comprise a Twist-Flex ™ upper part, said upper portion comprising an easy-to-grasp tongue-type handle in such a way that the container can be opened, for example, by tapping the tongue manually. The upper Twist-Flex ™ is advantageous in that it allows to distribute the solution, prevents spillage and eliminates the need to open the container by cutting the top, or similar aspects, thereby reducing cross-contamination. One or more of the semi-permeable single dose unit containers may be pre-packaged in an aluminum foil pouch, such that the foil provides a protective barrier against environmental contaminants and light. Such as a barrier that improves the shelf life and stability of the inhalation solution.

In another alternative embodiment, the present invention comprises a suitable system and / or inhalation equipment previously packaged for patients suffering from COPD. Said pre-packaged system and / or equipment comprises: (a) one or more single dose units of a therapeutically effective amount of albuterol and ipratropium; (b) administration instructions for the use of said dosage unit in the form of a treatment for COPD; and (c) a distribution container previously filled with the one or more dose units of albuterol and ipratropium. In another alternative embodiment, the pre-packaged inhalation system or equipment of the present invention provides one or more bottles of previously mixed single dose, previously measured unit comprising a therapeutically effective amount of albuterol and ipratropium for the treatment of associated bronchospasm. with COPD, and instructions for using them. In an alternative embodiment, the present invention is directed to a therapeutic system and / or equipment previously packaged to induce bronchodilation or provide relief of bronchospasm in a patient suffering from chronic obstructive pulmonary disease, wherein the previously packaged therapeutic system comprises: (a) one or more distributing containers; wherein the one or more containers are each pre-filled with approximately 3 ml of a previously sterilized aqueous solution, free of chlorinated benzalkonium, previously mixed previously measured; wherein the dosage of albuterol is approximately 2.5 mg and the dosage of ipratropium bromide is approximately 0.5 mg; the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a large shelf life period; (b) one or more labels with indications therein, wherein the indication comprises the dosage efficacy, administration, contraindications, and adverse reaction data pertaining to the inhalation solution in each of the one or more containers; (c) wherein the contraindication data comprises data indicating that the inhalation solution in each of the one or more containers is contraindicated for humans with hypersensitivity to atropine and derivatives thereof; and (d) where the adverse reaction data comprises data indicating that the precipitation or impairment of acute angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, wheezing, exacerbation of the symptoms of chronic obstructive pulmonary disease , lethargy, chronic pain, blushing, upper respiratory tract infection, palpitations, flare deviation, high heart rate, sinusitis, back and throat pain that may occur after administration of the inhalation solution in one or more containers.

The dose and administration data may comprise data indicating that the recommended dose of the inhalation solution in each of the one or more containers is approximately 2.5 mg of albuterol and approximately 0.5 mg of ipratropium bromide in 3 ml of a solution aqueous administered 4 times a day by nebulization with up to 2 additional recommended doses allowed per day, if necessary. Also, the adverse reaction data may comprise data indicating the immediate hypersensitivity reactions for the inhalation solution in each of the one or more containers that may occur after administration of the inhalation solution, wherein said hypersensitivity reactions comprise urticaria, angioedema, rash, pruritis, lower pharynx, edema, bronchospasm and anaphylaxis. Adverse reaction data may also comprise indication data that allergic type reactions may occur after administration of the inhalation solution, in the one or more containers, which include, rash, pruritis and urticaria. The adverse reaction data may additionally comprise data indicating a list of one or more adverse events that may occur after administration of the inhalation solution, wherein said events include chest pain, diarrhea, indigestion, nausea, muscle cramping in the legs, bronchitis, lung disease, pharyngitis, pneumonia and urinary tract infection. In another alternative embodiment, the previously packaged therapeutic system and / or equipment present for the treatment of bronchospasm in a patient suffering from chronic obstructive pulmonary disease may comprise: (a) one or more distribution containers; the one or more containers are pre-filled each with 3 ml of a sterilized aqueous solution previously measured, previously mixed stable, free of benzalkonium chloride, where the inhalation solution consists of sodium chloride, water, edetate of disodium, acid for adjusting the pH of the inhalation solution to about 4, and a dose unit of a therapeutically effective amount of albuterol and ipratropium bromide, wherein the amount of albuterol is about 2.5 mg and the amount of bromide ipratropium is approximately 0.5 mg; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; said inhalation solution has a high shelf life period; (b) one or more labels with indications therein; wherein the indications comprise efficacy, dosage, administration, contraindication and adverse reaction data pertaining to the inhalation solution in each of the one or more containers; (c) wherein the dose and administration data comprise data indicating that the recommended dose of the inhalation solution in each of the one or more containers is approximately 2.5 mg of albuterol and approximately 0.5 mg of ipratropium bromide in 3 ml of an aqueous solution administered 4 times a day by nebulization with up to 2 additional doses recommended per day, if necessary; (d) wherein the contraindication data comprises data indicating that the inhalation solution in each of the one or more containers is contraindicated for humans with hypersensitivity to atropine and derivatives thereof; (e) wherein the adverse reaction data comprises data indicating immediate hypersensitivity reactions to the inhalation solution in each of the one or more containers may occur after administration of the inhalation solution, wherein said hypersensitivity reaction includes urticaria, angioedema, rash, pruritis, lower pharynx, edema, bronchospasm, and anaphylaxis; (f) wherein the adverse reaction data comprises data indicating that allergic-type reactions can occur after administration of the inhalation solution in the one or more containers; wherein said allergic-type reaction includes rash, pruritis, and urticaria; (g) where the adverse reaction data comprises data indicating the precipitation or impairment of acute angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, wheezing, exacerbation of the symptoms of chronic obstructive pulmonary disease, lethargy, chronic pain, flushing, upper respiratory tract infection, palpitations, flare deviation, elevated heart rate, sinusitis, back and throat pain that may occur after administration of the inhalation solution in the one or more containers; and (h) the adverse reaction data includes a list of the one or more adverse events that may occur after administration of the inhalation solution in each of the one or more containers; Adverse events include chest pain, diarrhea, indigestion, nausea, muscle cramps in the legs, bronchitis, lung disease, pharyngitis, pneumonia, and urinary tract infection. The pre-packaged inhalation system and / or equipment may be provided in one of any number of ways, including, but not limited to, a box containing one or more pre-packaged dose unit jars or a box containing packages individual or comprising bags comprising one or more bottles of dosage unit. For example, in Figure 5, a modality of a previously packaged system and / or equipment unified to treat COPD in patients is illustrated. Specifically, Figure 5 illustrates support packages (10). The support package (10) can include, but not limited to, a box, cardboard or any other closed container. The support package comprises one or more previously packaged distribution containers, previously filled (21-25). Each container comprises a previously measured inhalation solution, previously mixed. The inhalation solution comprises a dose unit of a therapeutically effective amount of albuterol and ipratropium to treat COPD. The inhalation solution can be provided in a sterilized and / or BAC-free form. The support package (10) can also incorporate one or more labels (13) therein. One or more labels (13) may comprise indications (14) indicating that the inhalation solution may be used to alleviate the symptoms associated with COPD, such as broncho-spasm. The label may also comprise indications (15), which provide instructions for using the inhalation solution to alleviate said symptoms. As used in the present description, the term "indications" includes, but is not limited to, literature, photographs, drawings, symbols and / or forms. A non-limiting example of the indications that may appear on the one or more labels (13) is shown in Figure 7. The one or more labels may be placed on one or more surfaces of the support package (10) or a separate sheet , or any combination thereof. The support pack (10) can also incorporate a lid (16) to enclose the packing material therein. The system and / or equipment of the present invention may also include a label and / or instructions designed to facilitate the user's understanding. For example, in one embodiment, a system and / or equipment of the present invention comprises the packaging material containing one or more pre-packaged flasks comprising a previously measured, previously mixed, sterilized dose unit of an inhalation solution comprising a therapeutically effective amount of albuterol and ipratropium. The packaging material may additionally comprise a label indicating that each bottle can be used with a nebulizer for the relief of symptoms associated with COPD, such as bronchospasm. Said instructions may also include instructions for the dosage for each nebulizer treatment, as well as the administration instructions, such as by means of a nebulizer. The instructions may be placed on one or more surfaces of the packaging material therein, or the instructions may be provided on a separate sheet, or in any combination thereof. The present invention is also directed to a method for treating symptoms associated with COPD, including broncho-spasm, wherein a therapeutically effective amount of albuterol and ipratropium can be administered as a unit dose. Said dose unit can have the form of a nebulizer solution. In another embodiment, the present invention is directed to a method for inducing bronchodilation or providing relief of bronchospasm in a patient suffering from chronic obstructive pulmonary disease, wherein said method comprises the steps of: (a) providing the patient with a pre-packaged therapeutic system comprising: one or more distributing containers; the one or more containers are each previously filled with about 3 ml of a sterilized, previously measured, previously measured, previously mixed aqueous benzalkonium chloride-containing inhalation solution comprising a dose unit of a therapeutically effective amount of albuterol and ipratropium bromide; wherein the amount of albuterol is about 2.5 mg and the amount of ipratropium bromide is about 0.5 mg; the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; the inhalation solution in each of the one or more containers has a long shelf life; (b) providing the patient or person making the prescription dosing data, administration, contraindication and adverse reaction data of the therapeutic system belonging to the inhalation solution in each of the one or more containers; (c) wherein the contraindication data comprises data indicating that the inhalation solution in each of the one or more containers is contraindicated for humans with hypersensitivity to atropine and derivatives thereof; and (d) where the adverse reaction data comprises data indicating that the precipitation and deterioration of acute angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, wheezing, exacerbation of the symptoms of obstructive pulmonary disease. chronic, lethargy, chronic pain, flushing, upper respiratory tract infection, palpitations, flare deviation, elevated heart rate, sinusitis, back and throat pain that may occur after administration of the inhalation solution in one or more containers . In the present method, the dose and administration data can inform the patient or person making the prescriptions of the recommended dose of the inhalation solution in each of the one or more containers is approximately 2.5 mg of albuterol and 0.5 mg of Ipratropium bromide in 3 ml of an aqueous solution administered four times a day by nebulization with up to 2 additional recommended doses allowed per day, if necessary. The adverse reaction may also inform the patient or the prescribing person that immediate hypersensitivity reactions to the inhalation solution in each of the one or more containers may occur after administration of the inhalation solution, wherein said reactions of hypersensitivity include hives, angioedema, rash, pruritis, lower pharynx, edema, bronchospasm, and anaphylaxis. Adverse reaction data may also inform the patient or prescriber that allergic reactions may occur after administration of the inhalation solution, in one or more containers, including rash, pruritis and urticaria. Also, the adverse reaction data may include a previously printed list of one or more adverse events that may occur after administration of the inhalation solution, wherein said events include chest pain, diarrhea, indigestion, nausea, muscle cramping in the legs, bronchitis, lung disease, pharyngitis, pneumonia and urinary tract infection. In another alternative embodiment, the present invention is directed to a method for inducing bronchodilation or providing relief of bronchospasm in a patient suffering from chronic obstructive pulmonary disease, wherein said method comprises the step of: (a) providing a patient the previously packaged therapeutic system, comprising: one or more distribution containers; wherein the one or more containers are pre-filled each with 3 ml of a previously measured, previously mixed, stable, sterilized aqueous solution of benzalkonium chloride-free inhalation; wherein the inhalation solution consists of sodium chloride, water, disodium edetate, and acid to adjust the pH of the inhalation solution to about 4, and a dose unit of a therapeutically effective amount of albuterol and ipratropium bromide, wherein the amount of albuterol is approximately 2.50 mg / 3 ml and the amount of ipratropium bromide is approximately 0.5 mg / 3 ml; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; (b) providing the patient or the person making the prescription with data on efficacy, dosage, administration, contraindication and adverse reaction of the previously packaged therapeutic system belonging to the inhalation solution in each of the one or more containers; (c) wherein the dosing and administration data inform the patient or person making the prescription that the recommended dose of the inhalation solution in each of the one or more containers is approximately 2.5 mg of albuterol and approximately 0.5 mg of bromide ipratropium in 3 ml of an aqueous solution administered 4 times a day by nebulization with up to 2 additional doses recommended per day, if necessary; (d) wherein the contraindication data comprises information indicating that the inhalation solution in each of the one or more containers is contraindicated for humans with hypersensitivity to atropine and derivatives thereof; (e) wherein the adverse reaction data informs the patient or person making the prescription that immediate hypersensitivity reactions to the inhalation solution in each of the one or more containers may occur after administration of the inhalation solution in the one or more containers, wherein said hypersensitivity reaction includes urticaria, angioedema, rash, pruritis, of the lower pharynx, edema, bronchospasm and anaphylaxis; (f) wherein the adverse reaction data inform the patient or person making the prescription that possible allergic-type reactions may occur after administration of the inhalation solution in the one or more containers, include, rash, pruritis , and urticaria; (g) where the adverse reaction data inform the patient and person making the prescription that precipitation or impairment of acute angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, panting, exacerbation of disease symptoms chronic obstructive pulmonary disease, lethargy, chronic pain, flushing, upper respiratory tract infection, palpitations, flare deviation, elevated heart rate, sinusitis, back and throat pain that may occur after administration of the inhalation solution in one or more containers; and (h) the adverse reaction data includes a previously printed list of one or more adverse events that may occur after administration of the inhalation solution in each of the one or more containers; where the adverse events include chest pain, diarrhea, indigestion, nausea, muscle cramps in the legs, bronchitis, lung disease, pharyngitis, pneumonia and urinary tract infection. In an alternative embodiment, the method of the present invention comprises the step of administering to the patient a therapeutically effective amount of albuterol and ipratropium. Said solution can also be previously packaged, previously mixed, previously measured, free of BAC and / or sterilized. Said solution can also be in a single dose unit bottle.

In another alternative embodiment, the method of the present invention comprises the step of administering to a patient in need thereof, an inhalation solution comprising a therapeutically effective amount of albuterol and ipratropium. The inhalation solution is administered by a nebulizer, more preferably a pressure nebulizer connected to an air compressor with a suitable air flow. In yet another alternative embodiment, referring to Figures 1 to 4, the method of the present invention comprises the steps of: (i) placing the inhalation solution comprising a therapeutically effective amount of albuterol and ipratropium (1) within a nebulizer cup (2). The nebulizer can be ignited by joining to compressed gas cylinders or an electrically driven compressor; (ii) using a "T" adapter (3) to adjust the cap of the nebulizer cup (4) to a nozzle (5) or mask (6); (iii) extracting the inhalation solution (1) by the velocity of a pressurized gas and the fragmentation thereof in a spray; (iv) passing the spray through the mouthpiece (S) or mask (6) to the patient (7) suffering from bronchospasm; and (v) the patient continues to aspirate until no more mist forms in the nebulizer chamber (8). This can happen in a period of approximately 5 to 15 minutes. In another alternative embodiment, the usual starting dose for patients may be approximately 2.50 mg of albuterol and 0.5 mg of ipratropium administered 3 or 4 times a day, as needed for nebulization. To administer these amounts of albuterol and ipratropium, the total contents of the bottle of a unit dose may be used (eg, about 3 mg / 3 ml of albuterol sulfate and 0.5 mg / 3 ml of ipratropium bromide). Preferably, the flow rate of the nebulizer is adjusted to administer albuterol and ipratropium for a period of 5 to 15 minutes. Additionally, in an alternative embodiment, the method of the present invention comprises the steps of: (i) preparing an inhalation solution comprising a therapeutically effective amount of albuterol and ipratropium by diluting one or more solutions comprising ipratropium or albuterol; and (ii) administering the inhalation solution to a patient in need thereof. The present invention also provides a method for making a previously packaged, sterilized, pre-mixed, previously measured and / or BAC-free inhalation solution comprising a single dose unit of a therapeutically effective amount of albuterol and ipratropium. In such embodiment, the method of the present invention comprises one or more of the following steps: (i) adding at least a therapeutically effective amount of albuterol and ipratropium in a carrier, such as water; (ii) sterilize the solution and seal the container. An osmotic adjustment agent can be added to adjust isotonicity. Preferably, the solution of the present invention is isotonic and an osmotic adjustment agent can be added to adjust the isotonicity of the solution from about 280 to about 320 mOsm / kg.

Additionally, an acid (for example, hydrochloride) can be added to adjust the pH of the solution to a level of from about 3.0 to about 5.0, preferably about 4.0. In another embodiment, a method for making an inhalation solution of the present invention comprises one or more of the following steps: (i) adding at least a therapeutically effective amount of albuterol and ipratropium in a carrier such as water, (ii) placing the mixture in a container, and sterilizing the mixture by steam sterilization, or any other sterilization means known in the art. Each mixture of albuterol and ipratropium is placed in a bottle, and then packed, stored and / or used directly. In this point, the resulting mixture is stable and after sterilization, it can be distributed, if necessary, in multiple mixtures, where each contains a dose unit of a therapeutically effective amount of albuterol and ipratropium. Osmotic adjustment agents, which may be used include, but are not limited to, sodium chloride, potassium chloride, zinc chloride, calcium chloride and mixtures thereof. Other osmotic adjusting agents may also include, but are not limited to, mannityl, glycerol and dextrose and mixtures thereof. In an alternative embodiment, the present invention may comprise from about 0.4 to about 1.0 weight percent of ionic salt. Preferably, the present invention comprises 0.9% by weight of an osmotic adjusting agent. In an alternative embodiment, the inhalation solution of the present invention can be prepared in the following manner: (i) adjusting a stainless steel formulation tank with a duct at the bottom and a triple mixer for mixing; (ii) fill the tank with approximately 95% of the required amount of purified USP water at a temperature between 18 ° C and 25 ° C; while it is mixing; (iii) adding USP EDTA, hydrochloric acid, and at least a therapeutically effective amount of albuterol sulfate USP and ipratropium bromide USP to the tank; (iv) continue mixing until all the chemical components are dissolved; (v) purified USP water is added to adjust the final volume, if necessary, thus producing a mixture of albuterol and ipratropium bromide. From the formulation tank, the mixture of albuterol and ipratropium is pumped through the sanitary administration lines directly into a forming-filling-sealing machine (FFS). The mixture of albuterol and ipratropium passes through the 0.2 micron sterilization cartridge filter, and subsequently into the reserve tank, through a second 0.2 micron sterilization cartridge filter to the filling nozzles inside the bath compartment of sterilized air, and subsequently, within the bottles formed of low density polyethylene (LDPE). The mixture of albuterol and ipratropium is introduced in a sterilized manner into the bottles, such that each bottle contains a single dose unit of a therapeutically effective amount of albuterol. The filled bottles are then sealed. The FFS machine can form, fill and seal the bottles in a continuous operation under aseptic conditions, thereby producing a sterilized product. For example, the bases of five filled jars (Figure 6) can be over-wrapped inside laminated foil pouches protected using an automatic wrapping machine. Six to twelve such bags can then be packaged in a cardboard base, thus forming a previously packaged therapeutic system for the treatment of COPD in patients. A label and the appropriate instructions can be added to the cardboard base. The present invention is also directed to a method for forming a nebulizer dose unit solution comprising the step of: (i) preparing a mixture containing a therapeutically effective amount of albuterol and ipratropium bromide in a pharmaceutically effective carrier. Said mixture is suitable for nebulization in a nebulizer. In an alternative embodiment, the present invention also comprises a device for use in relieving symptoms associated with COPD, including bronchospasm. Said device may take the form of a label, with written instructions or any other form to incorporate indications therein. The device may comprise indications, which indicate that a patient suffering from the symptoms associated with COPD can be treated with at least one previously packaged, sterilized, pre-mixed, previously measured and / or BAC-free inhalation solution comprising a dose unit of a therapeutically effective amount of albuterol and ipratropium in a single bottle. The inhalation solution is suitable for nebulization in a nebulizer. The device may also comprise indications, which provide instructions for using the inhalation solution to treat such symptoms in patients.

EXAMPLES To evaluate the efficacy and safety of the inhalation solution of the present invention, a double blind randomized, positive control experiment was performed. The design, results and conclusion of the study are shown in more detail later.

PATIENTS Initially, a total of 863 patients were randomly distributed to be registered in the experiment. To have the ability to be chosen in the registry, patients had to meet the criteria described in Table 6.

TABLE 6 INCLUSION / EXCLUSION CRITERIA Design element Description Inclusion criteria • Diagnosis with COPD with a FEVi between 25% and 65% of the expected normal value. • Age > 40 years • Regular use of one or more bronchodilators for a minimum of 3 months before being registered • History of smoking at least 10 packs per year. • Ability to abstain from the use of theophylline, salmeterol and oral β2 agonists during the experiment (as judged by the researcher). • Ability to safely complete a 6-minute walk • Good disposition to provide informed consent Exclusion criteria • Diagnosis of anthracosis, silicosis any basic tissue disease that can not be attributed to COPD, polycythemia or pulmonary, hypoxia or a primary diagnosis which can be attributed to allergic rhinitis, atopy or COPD. • Urinary disease of clinically significant obstruction, acute angle glaucoma, unstable angina pectoris or myocardial infarction in the last 6 months, known drug abuse within the last 12 months, or hospitalization due to pulmonary exacerbation within the last 2 months • Known hypersensitivity to any component of the study medications • Use of investigational drug within 30 days of the first dose of medication study • Pregnancy or lactation INTERVENTIONS The doses of each individual agent and the combination of ipratropium and albuterol are shown in Table 7 below. All study medications were administered 4 times a day (ideally, every 6 hours) by inhalation using a Pari LC Plus ™ nebulizer and the Pari Proneb ™ compressor. The concomitant use of bronchodilators was restricted during the experiment. Steroidal oral and inhaled use was allowed throughout the experiment, allowing the dose to remain constant.

TABLE 7 EFFECTIVENESS OF RESULTS Of the 863 patients who were randomized and started treatment, 289 withdrew prematurely from the experiment, including 28 patients who did not meet the inclusion / extrusion criteria and were inadequately recorded. A total of 663 patients received both the inhalation solution of the present invention and at least one medication different from the study and completed at least one post-FEV dose measurement. These subjects contributed to the 647 comparisons that they can be evaluated in each portion of the main analysis, such that most patients completed the treatment in the three study medications. The main efficacy variable was the dose change prior to the peak FEV-i measured within a period of 3 hours after dosing during the cross-over phase of the experiment. As can be seen in Table 8, the average increase in FEV-? was significantly greater for the combination of albuterol and ipratropium than for any agent used alone. The improvement for the combination over albuterol was only 23.6% and over ipratropium it was only 37.2%. The time transition response of FEVi is shown in Figure 8.

TABLE 8 Efficacy results in the crossing phase During the parallel phase of the experiment, separate groups of patients self-administered only one of the three study medications during the last 6 weeks of the study. The results for the results produced from the parallel phase are essentially identical to the crossing phase. The combination of albuterol and ipratropium maintained the same magnitude of superiority over each component medication only that has been observed during the cross-over phase in the response of the SECURITY / TOLERANCE Adverse reactions concerning the combination of albuterol and ipratropium were evaluated from the clinical experiments described above. Adverse events arising from the treatment that were reported by 1% or more of the patients were summarized by medication in Table 9. As can be seen, there were no differences between the combination of albuterol and ipratropium and the individual medication in the incidence of patients with adverse events through the body systems.

TABLE 9 Reports of adverse event (Adverse events occurring in > 1% of the treatment group (s) and where the treatment combination showed the highest percentage).

Additional adverse reactions reported in more than 1% of patients treated with the combination of albuterol and ipratropium included constipation and voice disturbances. The Figures and inclusions of the present disclosure were presented for illustrative purposes only. These are not intended to limit the scope of the present invention. Additionally, it should be understood that various changes and modifications to the preferred embodiment currently described in the present description will be apparent to those skilled in the art. Said changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing the advantages that accompany it. Accordingly, it is intended that said changes and modifications be covered by the appended Claims. Also, the present invention may suitably comprise, consist of or consist essentially of the elements described in the present description in addition, and the present invention described in the present invention may be practiced adequately in the absence of any element which is not described specifically in the present description.

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1. - An inhalation solution comprising: a previously measured, previously mixed aqueous formulation comprising a single dose unit of a therapeutically effective amount of albuterol and ipratropium bromide to induce bronchodilation or provide relief of bronchospasm in subjects suffering from disease chronic obstructive pulmonary, wherein the amount of albuterol in the inhalation solution ranges from about 0.60 mg to about 5.0 mg and the amount of ipratropium bromide ranges from about 0.01 mg to about 1.0 mg; where the solution is provided in a single container. 2.- The inhalation solution in accordance with the Claim 1, further characterized in that the inhalation solution is sterilized. 3. The inhalation solution according to claim 1, further characterized in that the inhalation solution is free of benzalkonium chloride. 4. The inhalation solution according to claim 1, further characterized in that the pH of the inhalation solution ranges from about 3.0 to about 4.0. 5. The inhalation solution according to claim 1, further characterized in that the pH of the inhalation solution is about 4.0. 6. - The inhalation solution according to claim 1, further characterized in that the albuterol is in the form of an acid addition salt thereof. 7. The inhalation solution according to claim 6, further characterized in that the acid addition salt of albuterol is albuterol sulfate. 8.- The inhalation solution in accordance with the Claim 1, further characterized in that the albuterol is in the form of a racemic mixture. 9. - The inhalation solution according to claim 1, further characterized in that the amount of albuterol in the inhalation solution ranges from about 2.00 mg to about 3.00 mg. 10. The inhalation solution according to claim 1, further characterized in that the amount of albuterol in the solution is about 2.5 mg. 1 1.- The inhalation solution in accordance with the Claim 1, further characterized in that the inhalation solution is suitable for nebulization in a nebulizer. 12. The inhalation solution according to claim 1, further characterized in that said nebulizer is selected from the group consisting of a pressure nebulizer, an ultrasonic nebulizer and an aspiration activated nebulizer. 13. An inhalation solution comprising: a previously measured, previously mixed sterilized aqueous formulation, free of benzalkonium chloride comprising a single dose unit of a therapeutically effective amount of albuterol and ipratropium bromide to induce bronchodilation or alleviate the broncho-spasm in subjects suffering from chronic obstructive pulmonary disease, wherein the amount of albuterol in the solution is approximately 2.50 mg and the amount of ipratropium bromide is approximately 0.5 mg, wherein the solution is provided in a single container and wherein the inhalation solution is suitable for nebulization in a nebulizer. 14. The use of the inhalation solution of claim 1, for preparing a medicament for inducing bronchodilation or providing relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease. 15. The use as claimed in Claim 14, wherein the inhalation solution is sterilized when it is administrable to the subject. 16. The use as claimed in Claim 14, wherein the inhalation solution is free of benzalkonium chloride. 17. - The use as claimed in Claim 14, wherein the albuterol is in the form of an acid addition salt thereof. 18. - The use as claimed in Claim 17, wherein the acid addition salt of albuterol is albuterol sulfate. 19. The use as claimed in Claim 14, wherein the albuterol is in the form of a racemic mixture. 20. The use as claimed in Claim 14, wherein the amount of albuterol in the medicament ranges from about 2.0 mg to about 3.0 mg. 21. The use as claimed in Claim 14, wherein the amount of albuterol in the medicament is about 2.5 mg. 22. The use as claimed in Claim 14, wherein the medicament is administrable to the subject by nebulization. 23. The use of the inhalation solution of Claim 13, for preparing a medicament for inducing bronchodilation or providing relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease, wherein said medicament is administrable by nebulization. 24. The use of the inhalation solution of Claim 1, for preparing a medicament for inducing bronchodilation or providing relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease. 25. - A device for treating bronchospasm in a subject suffering from chronic obstructive pulmonary disease, said equipment comprising: (a) one or more containers; wherein said one or more containers each comprise a premeasured, previously measured, aqueous inhalation solution comprising a single dose unit of a therapeutically effective amount of albuterol and ipratropium bromide; wherein the amount of albuterol in the solution ranges from about 0.60 mg to about 5.00 mg and the amount of ipratropium bromide in the solution ranges from about 0.01 mg to about 1.00 mg; wherein the solution is suitable for nebulization in a nebulizer. 26. - The equipment according to claim 25, further characterized in that the inhalation solution is sterilized. 27. The equipment according to claim 25, further characterized in that the inhalation solution is free of benzalkonium chloride. 28. The kit according to claim 25, further characterized in that the amount of albuterol in the inhalation solution ranges from about 2.0 mg to about 3.0 mg of albuterol. 29. - The equipment according to claim 25, further characterized in that the amount of the albuterol in the inhalation solution is approximately 2.50 mg. 30. The equipment according to claim 25, further characterized in that it additionally comprises a label, which indicates that the inhalation solution can be used to relieve bronchospasm in subjects suffering from chronic obstructive pulmonary disease. 31. The equipment according to claim 25, further characterized in that it additionally comprises instructions for using the inhalation solution to relieve the bronchospasm associated with chronic obstructive pulmonary disease. 32. - The equipment according to claim 25, further characterized in that one or more containers are packed in the same bag or box. 33. - The equipment according to claim 32, further characterized in that said one or more containers comprise semi-permeable plastic and are packaged in an aluminum foil pouch. 34.- A team to treat broncho-spasm in a subject suffering from chronic obstructive pulmonary disease, said equipment comprises: (a) one or more containers; wherein said one or more containers each comprise a previously measured, previously mixed, benzalkon-free, sterilized, aqueous inhalation solution for use in a nebulizer, wherein said inhalation solution comprises a single dose unit of an amount therapeutically effective of albuterol and ipratropium bromide, wherein said amount of albuterol is about 2.50 mg and the amount of ipratropium bromide is about 0.5 mg; (b) a label, which indicates that the inhalation solution can be used to relieve bronchospasm in subjects suffering from chronic obstructive pulmonary disease; and (c) instructions for using the solution to alleviate said bronchospasm. 35. A previously packaged therapeutic system for treating bronchospasm in subjects suffering from chronic obstructive pulmonary disease, said pre-packaged therapeutic system comprises packaging material, wherein said packaging material comprises: (a) one or more containers; wherein said one or more containers each comprise a premeasured, previously measured, aqueous inhalation solution comprising a single dose unit in a therapeutically effective amount of albuterol and ipratropium bromide; wherein said amount of albuterol ranges from about 0.60 mg to about 5.0 mg and said amount of ipratropium bromide ranges from about 0.01 mg to about 1.0 mg; wherein the solution is suitable for nebulization in a nebulizer. 36. The therapeutic system previously packaged according to claim 35, further characterized in that said amount of albuterol ranges from about 2.00 mg to about 3.00 mg. 37. The therapeutic system previously packaged according to claim 35, further characterized in that said amount of albuterol is about 2.5 mg. 38. The therapeutic system previously packaged according to claim 35, further characterized in that the inhalation solution in each of the one or more containers is sterilized. 39. The therapeutic system previously packaged according to claim 35, further characterized in that the inhalation solution in each of the one or more containers is free of benzalkonium chloride. 40. The pre-packaged therapeutic system according to claim 35, further characterized in that said packaging material additionally comprises a label, which indicates that the inhalation solution can be used to relieve the bronchospasm associated with obstructive pulmonary disease. chronicle. 41. The therapeutic system previously packaged according to claim 35, further characterized in that said packaging material comprises instructions for using the solution to alleviate said bronchospasm. 42. A previously packaged therapeutic system for treating bronchospasm in subjects suffering from chronic obstructive pulmonary disease, said previously paid therapeutic system comprising the packaging material, wherein said packaging material comprises: (a) one or more containers; wherein the one or more containers each comprise a previously measured, previously measured, sterilized aqueous inhalation solution, mixed free of benzalkonium chloride for nebulization in a nebulizer; wherein the inhalation solution comprises a single dose unit of a therapeutically effective amount of albuterol and ipratropium bromide, wherein the amount of albuterol is about 2.50 mg and the amount of ipratropium bromide is about 0.5 mg; (b) a label indicating that the inhalation solution can be used to alleviate said bronchospasm; and (c) instructions for using the inhalation solution to relieve said bronchospasm. 43. A method for preparing a previously measured inhalation solution, previously mixed to treat bronchospasm in subjects suffering from chronic obstructive pulmonary disease; said method comprises the steps of: (a) placing a dose unit of a therapeutically effective amount of albuterol and ipratropium bromide in a vehicle, wherein the concentration of the albuterol in the vehicle ranges from about 0.60 mg to about 5.0 mg and the The concentration of ipratropium bromide in the transporter varies from 0.01 mg to 1.00 mg; and (b) providing the inhalation solution in a single container. 44. The method according to claim 43, further characterized in that it further comprises the step of adding hydrochloric acid to adjust the pH of the inhalation solution to a level ranging from about 3.0 to about 4.0. 45. The method according to claim 43, further characterized in that it further comprises the step of adding an osmotic agent to adjust the isotonicity of the inhalation solution; wherein the osmotic adjusting agent is selected from the group consisting of sodium chloride, potassium chloride, zinc chloride, calcium chloride and mixtures thereof. 46. The method according to claim 44, further characterized in that it further comprises the step of: (a) sterilizing the inhalation solution by passing it through a filter or by steam sterilization. 47. - The method according to claim 43, further characterized in that it additionally comprises the step of adding hydrochloric acid to adjust the pH of the inhalation solution in about 3.5. 48. - A device to be used in the relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease, the device having indications; the indications provide instructions for using a previously measured, previously mixed inhalation solution comprising a single dose unit of a therapeutically effective amount of albuterol and ipratropium bromide to treat said bronchospasm; wherein said amount of albuterol ranges from about 2.00 mg to about 3.00 mg of albuterol and the amount of ipratropium bromide ranges from 0.20 mg to 0.60 mg; wherein said solution is suitable for nebulization in a nebulizer. 49. A method for preparing a previously mixed, previously measured, stable aqueous nebulizer solution previously packaged to induce bronchodilation or provide relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease; said method comprises the steps of: (a) mixing water, EDTA, hydrochloric acid, an osmotic adjustment agent, albuterol sulfate and ipratropium bromide in a stainless steel tank at a temperature between 18 ° C and 25 ° C C to form a nebulizer solution; i) the final concentration of the albuterol and the ipratropium bromide in the nebulizer solution ranges from about 0.06% by weight to about 0.1% by weight of albuterol and from about 0.03% by weight to about 0.1% by weight of ipratropium; i) sufficient hydrochloric acid is added to the nebulizer solution, such that the pH of said solution is from about 3.0 to about 4.0; iii) sufficient osmotic adjustment agent is added to the nebulizer solution, such that the isotonicity of said solution is from about 280 to about 320 mOsm / kg; and b) passing the nebulizer solution through at least one sterilization filter; c) the sterile nebulizer solution is emptied into one or more low density polyethylene distribution containers, wherein each container is filled with approximately 3 ml of the previously measured, previously mixed, sterilized aqueous nebulizer solution comprising a unit dose of a therapeutically effective amount of albuterol and ipratropium bromide, wherein the dose of albuterol ranges from about 2.00 mg to about 3.00 mg and the dose of ipratropium bromide ranges from about 0.1 mg to about 1.0 mg; d) sealing sterilized each one of the one or more distribution containers containing the nebulizer solution; and wherein the stability of the nebulizer solution in one or more distribution containers is such that the shelf life of said solution is greater than 12 months; wherein the nebulizer solution is free of benzalkonium chloride. 50. The method according to claim 49, further characterized in that the albuterol is in the form of an acid addition salt thereof. 51. - The method according to claim 49, further characterized in that the acid addition salt of albuterol is albuterol sulfate. 52. The method according to claim 49, further characterized in that the albuterol is in the form of a racemic mixture. 53. The method according to claim 49, further characterized in that the nebulizer solution is suitable for nebulization in a pressure nebulizer, an ultrasonic nebulizer and a nebulizer activated by aspiration. 54. The method according to claim 49, further characterized in that the osmotic adjustment agent is selected from the group consisting of sodium chloride, potassium chloride, zinc chloride, calcium chloride and mixtures thereof. 55. - The method according to claim 49, further characterized in that the osmotic agent is sodium chloride. 56. The method according to claim 1, further characterized in that the osmotic adjustment agent is selected from the group consisting of mannitil, glycerol, dextrose and mixtures thereof. 57.- The method according to claim 49, further characterized in that the nebulizer solution in the one or more distribution containers comprises approximately from 0.4% by weight to approximately 1.0% by weight of the ionic salt. 58. The method according to claim 49, further characterized in that the nebulizer solution in the one or more distribution containers comprises approximately 0.9% of an osmotic adjustment agent. 59. - The method according to claim 49, further characterized in that it further comprises the step of: (a) packing the one or more distribution containers in a foil pouch. 60.- The method according to claim 49, further characterized in that the sterilization filter is a 0.2 micron sterilization cartridge filter. 61. - The method according to claim 49, further characterized in that it additionally comprises the step of passing the nebulizer solution through the second sterilization filter. 62. - The method according to claim 61, further characterized in that the second sterilization filter is a 0.2 micron sterilization cartridge. 63. - The method according to claim 49, further characterized in that the concentration of albuterol is about 0.083% by weight and the concentration of ipratropium bromide is about 0.017% by weight. 64. - The method according to claim 49, further characterized in that the osmotic capacity of the nebulizer solution ranges from about 282 mOsm / kg to about 285 mOsm / kg. 65. A method for preparing a pre-measured, stable, pre-packaged aqueous nebulizer solution previously packaged to induce bronchodilation or provide relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease; said method comprises the steps of: a) adding purified water within a stainless steel tank at a temperature between 18 ° C and 25 ° C; wherein said tank has a bottom conduit and a triple mixer for mixing; b) while it is. mixing, adding EDTA, hydrochloric acid and at least a therapeutically effective amount of albuterol sulfate and ipratropium bromide to the tank until dissolved; c) add purified water to adjust the final volume to a desired amount, thus forming the nebulizer solution; i) the final concentration of the albuterol and ipratropium bromide in the nebulizer solution ranges from about 0.06% by weight to about 0.1% by weight of albuterol and from about 0.03% by weight to about 0.1% by weight of ipratropium; ii) sufficient hydrochloric acid is added to the nebulizer solution such that the pH of said solution is from about 3.0 to about 4.0; iii) sufficient osmotic adjustment agent is added to the nebulizer solution, such that the isotonicity of said solution is from about 280 to about 320 mOsm / kg; d) passing the nebulizer solution through a sanitary administration line directly into a forming-filling-sealing machine (FFS); e) passing the nebulizer solution through a first 0.2 micron sterilization cartridge filter, subsequently passing the nebulizer solution into a reserve tank; and subsequently passing the nebulizer solution through a second 0.2 micron sterilization cartridge filter; f) said second cartridge filter is connected to at least one filling nozzle placed inside a sterilized air bath compartment; wherein the nebulizer solution is passed through the filling nozzle into one or more pre-formed low density polyethylene distribution containers; g) filling each of the one or more distribution containers with approximately 3 ml of the nebulizer solution, such that each container contains a sterilized dose unit of albuterol and ipratropium bromide, wherein said dose ranges from approximately 2.00 mg up to approximately 3.00 mg of albuterol and from 0.1 to 1.0 mg of ipratropium; h) sealing sterilized each one of the one or more distribution containers containing the nebulizer solution; e, i) wherein the stability of the nebulizer solution is such that the shelf life of said solution in one or more distribution containers is greater than 12 months; wherein the nebulizer solution is free of benzalkonium chloride. 66. - The method according to claim 65, further characterized in that the albuterol is in the form of an acid addition salt thereof. 67. - The method according to claim 65, further characterized in that the acid addition salt of albuterol is albuterol sulfate. 68. - The method according to claim 65, further characterized in that the albuterol is in the form of a racemic mixture. 69. - The method according to claim 65, further characterized in that the nebulizer solution is suitable for nebulization in a pressure nebulizer, an ultrasonic nebulizer and a nebulizer activated by aspiration. 70. The method according to claim 65, further characterized in that the osmotic adjusting agent is selected from the group consisting of sodium chloride, potassium chloride, zinc chloride, calcium chloride and mixtures thereof. 71. - The method according to claim 65, further characterized in that the osmotic adjustment agent is sodium chloride. 72. The method according to claim 65, further characterized in that the osmotic adjustment agent is selected from the group consisting of mannitil, glycerol, dextrose and mixtures thereof. The method according to claim 65, further characterized in that the nebulizer solution in the one or more distribution containers comprises from about 0.4% by weight to about 1.0% by weight of the ionic salt. 74. - The method according to claim 65, further characterized in that the solution of the nebulizer in the one or more distribution containers comprises approximately 0.9% by weight of an osmotic adjustment agent. The method according to claim 65, further characterized in that the one or more distribution containers are formed, filled and sealed in a continuous operation. 76. - The method according to claim 65, further characterized in that it further comprises the step of: (a) packing the one or more distribution containers in a foil pouch. 77. The method according to claim 65, further characterized in that the concentration of the albuterol is about 0.083% by weight and the concentration of ipratropium bromide is about 0.017% by weight. 78. The method according to claim 65, further characterized in that the osmotic capacity of the nebulizer solution is within the range of 282 mOsm / kg to about 285 mOsm / kg. 79. A previously packaged therapeutic system for inducing bronchodilation or providing relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease, comprising: (a) one or more distribution containers; the one or more containers are each pre-filled with approximately 3 ml of a previously measured, previously mixed aqueous solution, free of benzalkonium chloride, sterilized comprising a dose unit of a therapeutically effective amount of albuterol and ipratropium bromide; wherein the dose of albuterol is approximately 2.5 mg and the dose of ipratropium bromide is approximately 0.5 mg; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life; (b) one or more labels with indications therein, wherein the indications comprise the data of efficacy of the dose, administration, contraindications and adverse reaction pertaining to the inhalation solution in each of the one or more containers; (c) wherein the contraindication data comprises data indicating that the information solution in each of the one or more containers is contraindicated for humans with hypersensitivity to atropine and derivatives thereof; and (d) where the adverse reaction data comprises data indicating the precipitation or impairment of acute angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, wheezing, exacerbation of chronic obstructive pulmonary disease symptoms, lethargy, chronic pain, flushing, upper respiratory tract infection, palpitations, deviation of flavors, elevated heart rate, sinusitis, back and throat pain that may occur after administration of the inhalation solution in one or more containers. 80. The therapeutic system previously packaged according to claim 49, further characterized in that the albuterol is in the form of an acid addition salt. 81. The previously packaged therapeutic system according to Claim 50, further characterized in that the acid addition salt of albuterol is albuterol sulfate. 82. The pre-packaged therapeutic system according to claim 49, further characterized in that the dosing and administration data comprise data indicating that the recommended dose of the inhalation solution in each of the one or more containers is approximately 2.5. mg of albuterol and approximately 0.5 mg of ipratropium bromide in 3 ml of an aqueous solution administered 4 times per day by nebulization with up to 2 additional recommended doses allowed per day, if necessary. 83. The pre-packaged therapeutic system according to claim 49, further characterized in that the adverse reaction data comprises data indicating that immediate hypersensitivity reactions to the inhalation solution in each of the one or more containers may occur after the administration of the inhalation solution, wherein said hypersensitivity reactions comprise urticarias, angioedema, rash, pruritis, of the lower pharynx, edema, bronchospasm and anaphylaxis. 84. The pre-packaged therapeutic system according to claim 49, further characterized in that the adverse reaction data comprises data indicating that allergic-type reactions can occur after administration of the inhalation solution in one or more containers, They include rash, pruritis, and hives. 85. The therapeutic system previously packaged according to claim 49, further characterized in that the adverse reaction data comprises data indicating a list of one or more adverse events that may occur after administration of the inhalation solution, wherein Such adverse events include chest pain, diarrhea, indigestion, nausea, muscle cramps in the legs, bronchitis, lung disease, pharyngitis, pneumonia, and urinary tract infection. 86. A previously packaged therapeutic system for treating bronchospasm in a subject suffering from chronic obstructive pulmonary disease, comprising: (a) one or more distribution containers; wherein the one or more containers are pre-filled each with 3 ml of a previously measured aqueous inhalation solution, previously mixed, sterilized, stable, free of benzalkonium chloride; wherein the inhalation solution consists of sodium chloride, water, disodium edetate, an acid for adjusting the pH of the inhalation solution in about 4, and a dose unit of a therapeutically effective amount of albuterol and ipratropium bromide, wherein the amount of albuterol is about 2.5 mg and the amount of ipratropium bromide is about 0.5 mg; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein said inhalation solution has a high shelf life period; (b) one or more labels with indications therein; wherein the indication comprises information on efficacy, dosage, administration, contraindication and adverse reaction pertaining to the inhalation solution in each of the one or more containers; (c) wherein the dosing and administration data comprise data indicating that the recommended dose of the inhalation solution in each of the one or more containers is approximately 2.5 mg of albuterol and approximately 0.5 mg of ipratropium bromide in 3 ml. of an aqueous solution administered 4 times per day by nebulization with up to 2 additional doses recommended per day, if necessary; (d) wherein the contraindication data comprises data indicating that the inhalation solution in each of the one or more containers is contraindicated for humans with hypersensitivity to atropine and derivatives thereof; (e) wherein the adverse reaction data comprises data indicating that immediate hypersensitivity reactions to the inhalation solution in each of the one or more containers may occur after administration of the inhalation solution, wherein said reaction of hypersensitivity includes hives, angioedema, rash, pruritis, lower pharynx, edema, bronchospasm and anaphylaxis; (f) wherein the adverse reaction data comprises data indicating that allergic-type reactions can occur after administration of the inhalation solution in the one or more containers; wherein said type of allergic reaction includes rash, pruritis, and urticaria; (g) where the adverse reaction data comprises data indicating the precipitation or impairment of acute angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, wheezing, exacerbation of the symptoms of chronic obstructive pulmonary disease, lethargy, chronic pain, flushing, upper respiratory tract infection, palpitations, flare deviation, elevated heart rate, sinusitis, back pain and throat pain may occur after administration of the inhalation solution in one or more containers; and (h) the adverse reaction data includes a list of one or more adverse events that may occur after administration of the inhalation solution in each of the one or more containers; Adverse events include chest pain, diarrhea, indigestion, nausea, muscle cramps in the legs, bronchitis, lung disease, pharyngitis, pneumonia, and urinary tract infection. 87.- The use of one or more distribution containers; wherein the one or more containers is pre-filled each with about 3 ml of a previously measured aqueous solution, previously mixed, free of benzalkonium chloride, sterilized, comprising a dose unit of a therapeutically effective amount of albuterol and ipratropium bromide; wherein the amount of albuterol is about 2.5 mg and the amount of ipratropium bromide is about 0.5 mg; wherein the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer; wherein the inhalation solution in each of the one or more containers has a long shelf life; for preparing a previously packaged therapeutic system for inducing bronchodilation or providing relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease; (b) wherein the previously packaged therapeutic system provides the dose, administration, contraindication and adverse reaction data pertaining to the inhalation solution in each of the one or more containers; (c) wherein the contraindication data comprises data indicating that the inhalation solution in each of the one or more containers is contraindicated for humans with hypersensitivity to atropine and derivatives thereof; and (d) where the adverse reaction data comprise data indicating the precipitation or impairment of acute angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, wheezing, exacerbation of chronic obstructive pulmonary disease symptoms, lethargy, chronic pain, flushing, upper respiratory tract infection, palpitations, flare deviation, elevated heart rate, sinusitis, back pain and sore throat may occur after administration of the inhalation solution in one or more containers. 88. - The method according to claim 57, further characterized in that the albuterol is in the form of an acid addition salt. 89. The method according to claim 58, further characterized in that the acid addition salt of albuterol is albuterol sulfate. 90. - The method according to claim 57, further characterized in that the dosing and administration data inform the subject or person making the prescription that the recommended dose of the inhalation solution in each of the one or more containers is of approximately 2.5 mg of albuterol and 0.5 mg of ipratropium bromide in 3 ml of an aqueous solution administered 4 times a day by nebulization with up to 2 additional recommended doses allowed per day, if necessary. 91. - The method according to claim 57, further characterized in that the adverse reaction data inform the subject or person making the prescription that immediate hypersensitivity reactions to the inhalation solution in each of the one or more containers may occur after administration of the inhalation solution, wherein said hypersensitivity reactions include hives, angioedema, rash, pruritis, of the lower pharynx, edema, bronchospasm and anaphylaxis. 92. - The method according to claim 57, further characterized in that the adverse reaction data inform the subject or person making the prescription that allergic-type reactions can occur after administration of the inhalation solution in one or More containers, include rash, pruritis, and hives. 93. The method according to claim 57, further characterized in that the adverse reaction data includes a previously printed list of one or more adverse events that may occur after administration of the inhalation solution, wherein said adverse events comprise chest pain, diarrhea, indigestion, nausea, muscle cramps in the legs, bronchitis, lung disease, pharyngitis, pneumonia and urinary tract infection. 94. - The use of one or more distribution containers; wherein the one or more containers are pre-filled each with about 3 ml of a pre-measured, previously mixed, stable, sterilized aqueous solution, free of benzalkonium chloride; wherein the inhalation solution consists of water, disodium edetate, sodium chloride and an acid to adjust the pH of the inhalation solution in about 4, and a dose unit of a therapeutically effective amount of albuterol and ipratropium bromide, wherein the amount of albuterol is about 2.5 mg / 3 ml and the amount of ipratropium bromide is about 0.5 mg / 3 ml; the inhalation solution in each of the one or more containers is suitable for nebulization in a nebulizer, for preparing a previously packaged therapeutic system for inducing bronchodilation or providing relief of bronchospasm in a subject suffering from chronic obstructive pulmonary disease, said The method comprises the step of (a) wherein the previously packaged therapeutic system provides efficacy, dosing, administration, contraindication and adverse reaction data pertaining to the inhalation solution in each of the one or more containers; (b) wherein the dosing and administration data inform the subject or person making the prescription that the recommended dose of the inhalation solution in each of the one or more containers is approximately 2.5 mg of albuterol and approximately 0.5 mg of bromide ipratropium in 3 ml of an aqueous solution administered 4 times a day by nebulization with up to 2 additional doses recommended per day, if necessary; (c) wherein the contraindication data comprises data indicating that the inhalation solution in each of the one or more containers is contraindicated for humans with hypersensitivity to atropine and derivatives thereof; (d) wherein the adverse reaction data inform the subject or person making the prescription that immediate hypersensitivity reactions to the inhalation solution in each of the one or more containers may occur after administration of the inhalation solution in the one or more containers, wherein said hypersensitivity reaction includes urticarias, angioedema, rash, pruritis, of the lower pharynx, edema, bronchospasm and anaphylaxis; (e) wherein the adverse reaction data inform the subject or person making the prescription that possible allergic-type reactions may occur after administration of the inhalation solution in the one or more containers that include, rash, pruritis , and urticaria; (f) where the adverse reaction data inform the subject or person making the prescription that the precipitation or impairment of acute angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, gasping, exacerbation of disease symptoms Chronic obstructive pulmonary disease, lethargy, chronic pain, flushing, upper respiratory tract infection, palpitations, flare deviation, elevated heart rate, sinusitis, back pain and throat pain may occur after administration of the inhalation solution in the one or more containers; and (g) the adverse reaction data includes a list of one or more adverse events that may occur after administration of the inhalation solution in each of the one or more containers; Adverse events include chest pain, diarrhea, indigestion, nausea, muscle cramps in the legs, bronchitis, lung disease, pharyngitis, pneumonia, and urinary tract infection.