WO2022119429A1 - Medicamento de combinación fija para el control y manejo del dolor neuropático - Google Patents
Medicamento de combinación fija para el control y manejo del dolor neuropático Download PDFInfo
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- WO2022119429A1 WO2022119429A1 PCT/MX2020/050049 MX2020050049W WO2022119429A1 WO 2022119429 A1 WO2022119429 A1 WO 2022119429A1 MX 2020050049 W MX2020050049 W MX 2020050049W WO 2022119429 A1 WO2022119429 A1 WO 2022119429A1
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- Prior art keywords
- pharmaceutically acceptable
- vitamin
- fixed combination
- combination drug
- pain
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- 239000008117 stearic acid Substances 0.000 description 1
- 229940071138 stearyl fumarate Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
Definitions
- the present invention belongs to the field of health, in particular it refers to the pharmaceutical field in the manufacture of combination drugs for the control and management of neuropathic pain.
- vitamin B complex Studies on the potential use of vitamin B complex in the treatment of different types of pain and neuropathies are known (Levin, ER 1981; Mauro, GL, 2000; Hakim, M., 2018; Jayabalan, B., 2016; Suy Y ., 2005; Gazoni, FM, 2016), Studies on the analgesic capacity of the B vitamins thiamine, pyridoxine and cyanocobalamin (B1, B6, B12) that suggest the clinical utility that the vitamin B complex may have in the treatment of pain neuropathic after injury, inflammatory process and degeneration or in other disorders of the nervous system in humans have also been described (Wang, ZB., 2005).
- the Mexican patent MX 282576 protects in its main claim a pharmaceutical composition for oral administration of tablets in tablets, characterized in that it comprises: a first compartment that comprises therapeutically effective amounts of ketorolac, vitamin B1, vitamin B12, or their pharmaceutically acceptable salts, vehicle of compressibility, binder, diluent, unsightly, lubricant, plasticizer, and disintegrant; a second compartment comprising an insulating cover or layer formed of a coating polymer; and a third compartment comprising pyridoxine or its pharmaceutically acceptable salts and binding polymer binder.
- Mexican patent MX 293045 protects in its main claim a solid pharmaceutical formulation, in solution, suspension, or emulsion, characterized in that it comprises: a) meloxicam, b) cyanocobalamin, c) pyridoxine, d) thiamine, in addition to pharmaceutically acceptable excipients formulated in a single dosage unit.
- the invention deals with a fixed combination medicine to be used as an anti-inflammatory, antineuritic and in the control and management of pain, in particular, acute pain of moderate to severe intensity of diverse etiology, selected from: peripheral neuropathies, low back pain, sciatica, neck pain, radiculitis, postherpetic neuralgia, spondylitis, carpal tunnel syndrome, fibromyalgia, etc., of various etiologies such as inflammatory, drug, diabetic, alcoholic, nutritional, etc., and comprising a therapeutically effective amount of (a) a nonsteroidal anti-inflammatory agent (NSAID) or a pharmaceutically acceptable salt thereof; (b) an antineuritic agent or a pharmaceutically acceptable salt thereof; and (c) at least a pharmaceutically acceptable amount of a pharmaceutically acceptable excipient.
- NSAID nonsteroidal anti-inflammatory agent
- the nonsteroidal anti-inflammatory agent (NSAID) is dexketoprofen trometamol or a pharmaceutically acceptable salt thereof, while the
- the B complex is at least one of: vitamin B12 (cyanocobalamin), vitamin B1 (thiamin), vitamin B6 (pyridoxine), or a combination of any of them or their pharmaceutically acceptable salts thereof.
- Vitamin B1 is preferably present as thiamine mononitrate; and preferably vitamin B6 is presented as pyridoxine hydrochloride.
- At least one pharmaceutically acceptable excipient is selected from the group of: diluents, binders, disintegrants, emulsifiers or solubilizers, adsorbents and lubricants or a combination of any of them.
- the diluent is preferably corn starch in a pharmaceutically acceptable amount in the range of 3.0-10%;
- the binder is polyethylene glycol 6000 in a pharmaceutically acceptable amount in the range of 10-15%;
- the disintegrant is crospovidone in a pharmaceutically acceptable amount in the range of 2.0-5.0%;
- the solubilizer is poloxamer 188 in a pharmaceutically acceptable amount in the range of 5.0-10.0%;
- the adsorbent is magnesium aluminum silicate in a pharmaceutically acceptable amount in the range of 0.5-90%; and the lubricant is magnesium stearate in a pharmaceutically acceptable amount in the range of 0.25-5.0%.
- a preferred embodiment of the invention is the fixed combination medication preferably comprising a combination of dexketoprofen trometamol, cyanocobalamin, thiamine mononitrate and pyridoxine hydrochloride and pharmaceutically acceptable excipients, where the therapeutically effective amount of dexketoprofen trometamol is 12.5 to 75 mg/day. , preferably 36.91 mg (eq to 25 mg) and the therapeutically effective amount of vitamin B12 (cyanocobalamin), vitamin B1 (thiamin, mononitrate), and vitamin B6 (pyridoxine, hydrochloride) is 0.50, 100.00, and 50.00 mg, respectively.
- Solid dosage form is a solid dosage unit selected from the group consisting of tablet, lozenge, caplet, granules, lozenges, pills, capsules; preferably in capsule form.
- the manufacture of the combination drug includes the selection of unit operations, in order and time of execution, to control the different physicochemical properties of the drugs and that includes heating, granulation, cooling, mixing and sieving.
- the use of the fixed combination drug for the control and management of pain is described, where the pain is acute pain of moderate to severe intensity of diverse etiology.
- a therapeutically effective amount of (a) a nonsteroidal anti-inflammatory agent (NSAID), such as dexketoprofen trometamol, or a pharmaceutically acceptable salt thereof; (b) an antineuritic agent such as a combination of vitamins that make up the B group or complex as described above or a pharmaceutically acceptable salt thereof; and (c) at least one pharmaceutically acceptable excipient for the manufacture of a fixed combination medicament useful as an anti-inflammatory, antineuritic, and in the control and management of pain in an individual with pain.
- NSAID nonsteroidal anti-inflammatory agent
- antineuritic agent such as a combination of vitamins that make up the B group or complex as described above or a pharmaceutically acceptable salt thereof
- at least one pharmaceutically acceptable excipient for the manufacture of a fixed combination medicament useful as an anti-inflammatory, antineuritic, and in the control and management of pain in
- the fixed combination drug has greater efficacy for the control and management of pain in an individual.
- Figure 4 Average time courses on an arithmetic scale of both periods of the study of the plasma concentration of dexketoprofen up to the sample corresponding to 14 h.
- pharmaceutically acceptable salt is to be understood as a compound that retains the biological efficacy and properties of the given compound, and that is not biologically or otherwise undesirable (P. Heinrich Stahl and Camille G. Wermuth (Eds.) Pharmaceutical Salts Properties, Selection, and Use (International Union of Pure and Applied Chemistry), Wiley - VCH; 2nd Revised Edition (May 16, 2011)).
- Pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include, by way of example only, sodium, potassium, lithium, ammonium, calcium and magnesium salts. Salts derived from organic bases include, but are not limited to, primary, secondary, and tertiary amine salts.
- Suitable amines include, isopropylamine, trimethylamine, diethylamine, tri(isopropyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, tromethamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine , ethylenediamine, glucosamine, N-alkylglucamines, theobromine, purines, piperazine, piperidine, morpholine, N-ethylpiperidine, and the like.
- Salts derived from inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, acid phosphoric, and the like.
- Salts derived from organic acids include acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like.
- excipient should be understood as the ingredient that is part of the present pharmaceutical composition, among them are diluents, disintegrants, lubricants, coating, absorbents, among others.
- Stability It is the ability of a pharmaceutical product to retain its chemical, physical, microbiological and biopharmaceutical properties within specified limits throughout its shelf life.
- the present invention deals with an innovative stable drug that is adapted to be immediate release in a single dosage unit to be used as an anti-inflammatory, antineuritic and in the treatment, better control and management of pain in an individual, and at the same time solve a set of important technological challenges in the manufacture of said medicine due to the physicochemical properties and the difference in doses of the combination of the active ingredients that it comprises to guarantee the obtaining of a stable product for such purposes.
- a fixed combination medicament comprising a therapeutically effective amount of (a) a nonsteroidal anti-inflammatory agent (NSAID) or a pharmaceutically acceptable salt thereof; (b) an antineuritic agent or a pharmaceutically acceptable salt thereof; and (c) at least a pharmaceutically acceptable amount of a pharmaceutically acceptable excipient, and where the drug is presented in a solid, stable and immediate release pharmaceutical form.
- NSAID nonsteroidal anti-inflammatory agent
- the combination therapy in solid, stable, immediate-release pharmaceutical form for use in the control and management of pain comprises an agent non-steroidal anti-inflammatory drug (NSAID) which is dexketoprofen trometamol or a pharmaceutically acceptable salt thereof.
- NSAID non-steroidal anti-inflammatory drug
- the antineuritic agent is a combination of vitamins that make up the B group or complex, or pharmaceutically acceptable salts thereof.
- the B complex is at least one of: vitamin B12 (cyanocobalamin), vitamin B1 (thiamin), vitamin B6 (pyridoxine), or a combination of any of these or a pharmaceutically acceptable salt thereof; where vitamin B1 is presented as thiamine in its mononitrate form, while vitamin B6 is presented as pyridoxine, hydrochloride.
- NSAID non-steroidal anti-inflammatory agent
- the antineuritic agent is at least one or a combination of vitamins that make up the B group or complex, or pharmaceutically acceptable salts thereof selected from: vitamin B12 (cyanocobalamin), vitamin B1 (thiamin), vitamin B6 (pyridoxine), or a combination of any of them or their pharmaceutically acceptable salts thereof
- the technological complexity lies in the fact that there is light sensitivity of cyanocobalamin, thiamine and pyridoxine; as well as interaction due to the presence of moisture. Therefore, achieving stability through a dispersion medium in which the absorption of light and moisture is not affected, which is achieved through a water-free process and with materials that allow the protection of drugs without affect their release.
- the process lies in the selection of the unit operations, the order and the execution time to control the different physicochemical properties of the drugs, for which the critical operations of the manufacturing process are described below:
- heating with a heating time of 900s to 1200s, required to achieve granulation that allows drug protection by means of a physical barrier;
- the pharmaceutically acceptable excipients and/or carriers of the pharmaceutical composition of the present invention include, but are not limited to, at least one of: diluents, binders, disintegrants, emulsifiers or solubilizers, adsorbents and lubricants or a combination of any of them.
- diluents examples include adjusting and maintaining constant tablet weight, compaction and flow, include but are not limited to cellulose derivatives, such as microcrystalline cellulose, phosphate derivatives such as dibasic calcium phosphate, starch derivatives such as pregelatinized starch and corn starch, as well as, mannitol, xylitol, maltitol, lactitol, sorbitol, sucrose or a combination thereof.
- the diluent is preferably corn starch in a pharmaceutically acceptable amount in the range of 3.0-10.0%, preferably in a concentration of 7.5%.
- binders examples include, but are not limited to hypromellose (various grades), corn starch, cellulose derivatives (hydroxypropylcellulose, carboxymethylcellulose), hydrogenated vegetable oil derivatives, ethylene glycol derivatives (peg-300, peg-3000), gum derivatives (acacia gum), agar, alginate derivatives (alginic acid), calcium derivatives (calcium carbonate, calcium phosphate), carbomers, chitosan, povidone derivatives (copovidone, cropovidone, polyvidone).
- the binder is preferably polyethylene glycol 6000, which is selected in the present invention because it has a melting point of 55-63°C and avoids the use of water to obtain granules, and is found in a pharmaceutically acceptable amount. acceptable in the range of 10-15%, more preferably 2.87%.
- Pharmaceutically acceptable disintegrants include, but are not limited to, croscarmellose, cellulose derivatives such as hydroxypropylcellulose, carboxymethylcellulose, microcrystalline cellulose; povidone derivatives such as crospovidone, copovidone; starch derivatives such as pregelatinized starch, sodium starch glycolate, corn starch and modified potato starch.
- the disintegrant is preferably crospovidone, which is selected in the present invention for its high ability to rapidly absorb water, increase its volume and wetting capacity, providing a shorter disintegration time relative to other materials, in a pharmaceutically acceptable amount. acceptable in the range of 2.0-5.0%, preferably 4.98%.
- solubilizers examples include, but are not limited to polyethylene glycol derivatives and derivatives (polyoxethyl alkyl ether, hydrogenated castor oil), sodium lauryl sulfate, sorbitan esters, and benzalkonium chloride.
- the binder is preferably poloxamer 188, which is selected in the present invention because it improves the solubility and stability of the active ingredients of the combination drug and is in a pharmaceutically acceptable amount in the range of 5.0-10.0%, more preferably at 2.87%.
- adsorbents include but are not limited to aluminum derivatives (aluminum hydroxide, aluminum oxide, aluminum phosphate), clays or earths (talupugite, betonite, hectorite, kaolin, pectin), silica derivatives (calcium silicate, colloidal silicon dioxide, magnesium aluminum silicate), cellulose derivatives (microcrystalline cellulose, cellulose), magnesium derivatives (magnesium carbonate, magnesium silicate) and magnesium aluminum metasilicate due to their ability to adsorb wastewater into the solid pharmaceutical form or captured through the environment to improve the stability of the active ingredients.
- the adsorbent is preferably magnesium aluminum silicate in a pharmaceutically acceptable amount ranging from 0.5 to 90%, preferably 26.35%.
- Examples of pharmaceutically acceptable lubricants include, but are not limited to, magnesium stearate, zinc stearate, calcium stearate, stearic acid, monostearate, stearyl fumarate; talc and sulfated derivatives such as magnesium lauryl sulfate.
- the lubricant makes it possible to avoid sticking between the different tools during the compression process of the solid pharmaceutical form.
- the lubricant is preferably magnesium stearate for its slip characteristics in a pharmaceutically acceptable amount ranging from 0.25 to 5.0%, more preferably 0.95%.
- the fixed combination drug is in a single solid dosage unit that is selected from the group comprising a tablet, pill, caplet, granules, pills, pills, capsules.
- the preferred pharmaceutical form selected to dose the active ingredients was that of "capsules" due to its dose accuracy, in addition to the fact that it is an acceptable pharmaceutical form due to its easy administration, an alternative is tablets, however, given the rheological properties of the powder, it is more complex to carry out a compression process.
- the combination drug formulation comprises the following components according to Table 2.
- a preferred embodiment of the invention is the fixed combination medication preferably comprising a combination of dexketoprofen trometamol, cyanocobalamin, thiamine mononitrate and pyridoxine hydrochloride and pharmaceutically acceptable excipients, where the therapeutically effective amount of dexketoprofen trometamol is 12.5 to 75 mg/day. , preferably, 36.91 mg (eq to 25 mg) and the therapeutically effective amount of vitamin B12 (cyanocobalamin), vitamin B1 (thiamin, mononitrate), and vitamin B6 (pyridoxine, hydrochloride) is 0.50, 100.00 and 50.00 mg respectively.
- the bioavailability of the fixed combination drug was determined.
- a bioavailability comparison of dexketoprofen - Complex B against dexketoprofen (reference drug) at a dose of 25 mg was performed in healthy subjects, of both genders, under fasting conditions to characterize the pharmacokinetic parameters C max , AUC, T max , Ke , and T1/2 of dexketoprofen. Due to the innovation carried out in the process and formulation of the drug, it was possible to obtain a product with demonstrated stability through studies in accordance with current regulations in which the quality attributes were met during the evaluation period. Stability tests provide a means of comparing different formulations, packaging materials, or manufacturing processes in short-term experiments. As soon as the final formulation and manufacturing process are established, the manufacturer carries out a series of stability tests that will make it possible to predict the stability of the product or medicine in this case and to determine its shelf life and storage conditions.
- the heating stage begins in order to achieve the granulation of the mixture from point 1
- the cooling stage is carried out, which culminates in obtaining a temperature of 25°C to 30°C.
- the fixed combination medicament of a therapeutically effective amount of (a) a non-steroidal anti-inflammatory agent (NSAID) or a pharmaceutically acceptable salt thereof; (b) an antineuritic agent or a pharmaceutically acceptable salt thereof; and (c) at least a pharmaceutically acceptable amount of a pharmaceutically acceptable excipient; preferably a combination of dexketoprofen trometamol, cyanocobalamin, thiamine mononitrate and pyridoxine hydrochloride and pharmaceutically acceptable excipients, a bioavailability comparison study of dexketoprofen - complex B against dexketoprofen (reference drug) at a dose of 25 mg in healthy subjects, of both genders, under fasting conditions to characterize the pharmacokinetic parameters C max , AUC, T max , Ke, and T1/2 of dexketoprofen as well as to establish the frequency and type of adverse events presented with both formulations (reference drug A determined by the health authority, and test drug B prepared by Si
- the study design was crossover, 2 x 2, open, prospective and longitudinal, at a single dose of dexketoprofen 25 mg versus dexketoprofen 25 mg + vitamin B, with two treatments, two periods, two sequences with a period of elimination (washout) of 7 days and with a total of 36 healthy subjects, of both genders, under fasting conditions.
- the study design was proposed based on what is described in the Agreement that determines the type of test to demonstrate interchangeability of generic drugs. Based on this list, the type of test for the pharmaceutical form of complex B and dexketoprofen tablets is: Complex B, type A test: It does not require dissolution or bioequivalence tests. Dexketoprofen, test type C: Bioequivalence test.
- the drugs a tablet containing dexketoprofen 25 mg or a capsule containing dexketoprofen - vit-B complex, were administered orally according to the randomization sequence, after 10 hours of fasting and 4 hours before breakfast, with 250 mL of water at room temperature. Later they took 17 blood samples of approximately 4 mL each at the following times: 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 14.0 and 24.0 hours.
- the pharmacokinetic parameters of all the subjects were tabulated indicating the drug or formulation, arithmetic mean (X), standard deviation (SD), coefficient of variation (CV), geometric mean, median, minimum and maximum value. Per-individual plots of the concentration profile versus time and the mean plot of concentration + standard error versus time were included.
- Figure 4 shows comparatively the average time courses on an arithmetic scale of both periods of the study of the plasma concentration of dexketoprofen up to the corresponding sample at 14 h, in the subjects who received the reference drug or the test drug.
- the following table presents descriptive statistics for all relevant pharmacokinetic parameters for dexketoprofen in subjects receiving either the reference drug or the test drug.
- Table 7 Descriptive statistics of the ethical pharmacokinetic parameters for dexketoprofen.
- dexketoprofen - vit b complex 25 mg capsules
- SA de CV The overall exposure of dexketoprofen, as measured by the in the test formulation, dexketoprofen - vit b complex (25 mg capsules), from Laboratorios Silanes, SA de CV, showed compliance with the acceptance criteria of the bioequivalence statistical tests (confidence intervals classical 90% and Schuirmann's unilateral double test), of the reference drug (25 mg tablets).
- C max peak plasma concentration
- the invention deals with a fixed combination drug to be used as an anti-inflammatory, antineuritic and in the control and management of pain, in particular, acute pain of moderate to severe intensity of diverse etiology, selected from: peripheral neuropathies, low back pain, sciatica, neck pain, radiculitis, postherpetic neuralgia, spondylitis, carpal tunnel syndrome, fibromyalgia, etc., of various etiologies such as inflammatory, drug, diabetic, alcoholic, nutritional, etc., and comprising a therapeutically effective amount of (a ) a non-steroidal anti-inflammatory agent (NSAID) or a pharmaceutically acceptable salt thereof; (b) an antineuritic agent or a pharmaceutically acceptable salt thereof; and (c) at least a pharmaceutically acceptable amount of a pharmaceutically acceptable excipient.
- NSAID non-steroidal anti-inflammatory agent
- the medication combines in a single dosage unit the drugs dexketoprofen in a dose of 12.5 to 75 mg/day, preferably 36.91 mg (eq to 25 mg of dexketoprofen); and cyanocobalamin, pyridoxine hydrochloride and thiamine mononitrate with a dose of 0.5 mg, 50 mg and 100 mg respectively, representing a technological challenge given the properties of the drugs.
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- Animal Behavior & Ethology (AREA)
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Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA3199162A CA3199162A1 (en) | 2020-12-04 | 2020-12-04 | Fixed-dose combination drug for the control and management of neuropathic pain |
EP20964394.9A EP4268813A4 (en) | 2020-12-04 | 2020-12-04 | FIXED COMBINATION DRUG FOR THE CONTROL AND MANAGEMENT OF NEUROPATHIC PAIN |
US18/255,229 US20230414545A1 (en) | 2020-12-04 | 2020-12-04 | Fixed combination medicine for the control and management of neuropathic pain |
MX2022015334A MX2022015334A (es) | 2020-12-04 | 2020-12-04 | Medicamento de combinacion fija para el control y manejo del dolor neuropatico. |
PCT/MX2020/050049 WO2022119429A1 (es) | 2020-12-04 | 2020-12-04 | Medicamento de combinación fija para el control y manejo del dolor neuropático |
DO2023000094A DOP2023000094A (es) | 2020-12-04 | 2023-05-12 | Medicamento de combinación fija para el control y manejo del dolor neuropático |
CONC2023/0008893A CO2023008893A2 (es) | 2020-12-04 | 2023-07-04 | Medicamento de combinación fija para el control y manejo del dolor neuropático |
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Application Number | Priority Date | Filing Date | Title |
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PCT/MX2020/050049 WO2022119429A1 (es) | 2020-12-04 | 2020-12-04 | Medicamento de combinación fija para el control y manejo del dolor neuropático |
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WO2022119429A1 true WO2022119429A1 (es) | 2022-06-09 |
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PCT/MX2020/050049 WO2022119429A1 (es) | 2020-12-04 | 2020-12-04 | Medicamento de combinación fija para el control y manejo del dolor neuropático |
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Country | Link |
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US (1) | US20230414545A1 (es) |
EP (1) | EP4268813A4 (es) |
CA (1) | CA3199162A1 (es) |
CO (1) | CO2023008893A2 (es) |
DO (1) | DOP2023000094A (es) |
MX (1) | MX2022015334A (es) |
WO (1) | WO2022119429A1 (es) |
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WO2009109836A1 (es) | 2008-03-07 | 2009-09-11 | Laboratorios Senosian S.A. De C.V. | Formulación galénica oral que comprende ketorolaco y vitaminas del complejo b, en la que la vitamina b6 se encuentra en una capa externa separada del resto de principios activos |
WO2014098552A1 (es) * | 2012-12-19 | 2014-06-26 | Cecype Services S. De R.L. De C.V. | Composición farmacéutica que comprende la combinación de un agente antiinflamatorio no esteroideo, un agente adyuvante y un analgésico antineurítico, con efecto antinociceptivo |
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Also Published As
Publication number | Publication date |
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CA3199162A1 (en) | 2022-06-09 |
DOP2023000094A (es) | 2023-06-30 |
CO2023008893A2 (es) | 2023-07-10 |
EP4268813A1 (en) | 2023-11-01 |
MX2022015334A (es) | 2023-01-11 |
US20230414545A1 (en) | 2023-12-28 |
EP4268813A4 (en) | 2024-07-31 |
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