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JP-7857044-B2 - Composition containing ciprofloxacin and celecoxib

JP7857044B2JP 7857044 B2JP7857044 B2JP 7857044B2JP-7857044-B2

Inventors

  • ベン ヌーン，アロン
  • スターリング，ジェフリー
  • ヤコビー－ゼヴィ，オロン
  • コーエン ヴェレッド，シャロン

Assignees

  • ニューロセンス セラピューティックス リミテッド

Dates

Publication Date
20260512
Application Date
20221018
Priority Date
20211019

Claims (17)

  1. A tablet comprising celecoxib, ciprofloxacin or a pharmaceutically acceptable salt thereof, and low viscosity hydroxypropyl methylcellulose having a viscosity of 2 cP to 150 cP when measured as a 2% aqueous solution at 20°C , The tablet contains extragranular and intragranular components, and hydroxypropyl methylcellulose is present in the extragranular components, The tablets wherein pharmaceutically acceptable salts of celecoxib and ciprofloxacin are present in the granular components .
  2. The pharmaceutically acceptable salt of ciprofloxacin is ciprofloxacin hydrochloride, as described in claim 1.
  3. The tablet according to claim 1, wherein the hydroxypropyl methylcellulose has 28.0% to 30.0% methoxyl substitution and 7.0% to 12.0% hydroxypropoxyl substitution.
  4. The tablet according to claim 1, wherein the hydroxypropyl methylcellulose has 19.0% to 24.0% methoxyl substitution and 7.0% to 12.0% hydroxypropoxyl substitution.
  5. The tablet according to claim 1, wherein hydroxypropyl methylcellulose is present in an amount of 3% to 10% by weight of the tablet.
  6. The tablet according to claim 5, wherein hydroxypropyl methylcellulose is present in an amount of 5% by weight of the tablet.
  7. The tablet according to claim 1, wherein hydroxypropyl methylcellulose is present in an amount of 4% to 15% by weight relative to the weight of the pharmaceutically acceptable salts of celecoxib and ciprofloxacin, which are the active ingredients in the tablet.
  8. The tablet according to claim 7, wherein hydroxypropyl methylcellulose is present in an amount of 6% to 8% by weight relative to the weight of the active ingredient.
  9. The tablet according to claim 1, further comprising a filler selected from the group consisting of a soluble filler, a non-soluble filler, and a mixture of a soluble filler and a non-soluble filler.
  10. The tablet according to claim 9 , wherein the filler is microcrystalline cellulose, lactose, mannitol, or a combination thereof.
  11. The low-viscosity hydroxypropyl methylcellulose has a viscosity of 50 cP when measured as a 2% aqueous solution at 20°C, as described in claim 1.
  12. The tablet according to claim 1, wherein the ratio of the weight of celecoxib to the weight of ciprofloxacin free base is 1:1 to 1:100.
  13. The tablet according to claim 12 , wherein the ratio of the weight of celecoxib to the weight of ciprofloxacin free base is 1:10 to 1:25.
  14. The tablet according to claim 13 , wherein the ratio of the weight of celecoxib to the weight of ciprofloxacin free base is 1:10.
  15. The tablet according to claim 1, wherein when the tablet is placed in a Type II apparatus at 75 RPM and 37°C in 900 ml of pH 4.5 acetate buffer containing 1% SLS, 10% to 30% of ciprofloxacin and celecoxib are released in 1 hour, 30% to 70% of ciprofloxacin and celecoxib are released in 4 hours, and more than 85% of ciprofloxacin and celecoxib are released in 12 hours.
  16. The tablet according to claim 1, wherein when the tablet is administered to a human subject with food and water for 7 days, the Tmax of celecoxib in the subject's serum is within the range of 80% to 125% of the Tmax of ciprofloxacin in the subject's serum.
  17. a. To form granules containing celecoxib and ciprofloxacin or pharmaceutically acceptable salts thereof; b. Adding low-viscosity hydroxypropyl methylcellulose, which has a viscosity of less than 150 cP when measured as a 2% aqueous solution at 20°C, to granules to form a mixture; and c. Compressing the mixture to form tablets. A method (step) for manufacturing the tablets according to claim 1, including the method (step).

Description

Cross-reference of related applications: We claim interest in U.S. Provisional Patent Application No. 63/257,130, filed October 19, 2021, the contents of which are incorporated herein by reference in their entirety. Dosage forms comprising ciprofloxacin or its pharmaceutically acceptable salts and celecoxib are provided. Ciprofloxacin is an antibiotic sold in many countries for the treatment of various bacterial infections and can be administered orally and through other routes. It is available in salt form, such as hydrochloride, and has the following structure: Celecoxib is a COX-2 inhibitor administered orally and is used to treat pain or inflammation associated with various conditions. The structure of celecoxib is as follows: PCT Patent Application Publication (WO) 2018/235082 (incorporated herein by reference) discloses a combination of ciprofloxacin and celecoxib for the treatment of various motor neuron diseases, including but not limited to amyotrophic lateral sclerosis (ALS). International Patent Application Publication No. 2018/235082 Figure 1 shows a graph of normalized mean plasma concentrations over time in healthy volunteers after administration of ciprofloxacin and celecoxib, compared to day 7 of administration, comparing administration with a combination tablet containing ciprofloxacin and celecoxib (PrimeC) and administration with a reference tablet (Ref). Detailed Explanations Unless otherwise specified, technical terms will be used according to their conventional usage. For definitions of general terms in molecular biology, please refer to: Benjamin Lewin, Genes V, Oxford University Press, 1994 (ISBN 0-19-854287-9); Kendrew et al., (eds.), The Encyclopedia of Molecular Biology, published in 1994 by Blackwell Science Ltd. (ISBN 0-632-02182-9); and Robert A. Published in 1995 by Meyers (ed.), *Molecular Biology and Biotechnology: A Comprehensive Desk Reference*, VCH Publishers, Inc. (ISBN 1-56081-569-8). Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art in which this disclosure pertains. The singular terms “a,” “an,” and “the” include plural reference terms unless explicitly indicated otherwise in the context. Similarly, the word “or” is intended to include “and” unless explicitly indicated otherwise in the context. Furthermore, it should be understood that all base sizes or amino acid sizes and all molecular weight or molecular mass values given for nucleic acids or polypeptides are approximate and provided for illustrative purposes only. Methods and materials similar or equivalent to those described herein may be used to carry out or test this disclosure, but preferred methods and materials are described below. The term “comprise” means “include.” The abbreviation “e.g.” is derived from the Latin “exempli gratia” and is used herein to indicate non-limiting examples. Therefore, the abbreviation "e.g." is synonymous with the term "for example." In the event of any inconsistency, this specification, including the explanation of terms, shall prevail. Furthermore, all materials, methods, and examples are illustrative and not intended as limitations. Extragranular: In the tablet formation process, granules containing the active ingredient combined with at least one excipient are often formed. The granulation process converts fine powder into freely flowing, compressible, dust-free granules. These granules can then be blended with further excipients or active ingredients. The final blend is either filled into capsules or compressed into tablets. The term "extragranular" refers to the non-granular portion of a tablet. Intragranular: The portion of a tablet composition located within a granule, formed through a granulation process. Pharmaceutically acceptable salts: "Salt" refers to a salt of an active compound such as ciprofloxacin, modified by forming an acid acid or base salt of the compound. This refers to relatively non-toxic inorganic and organic acid or base addition salts of the compound of the present invention. These salts can be prepared in situ during the preparation of pharmaceutical dosage forms, or individually by reacting the purified compound of the present invention in the form of a free base with a suitable organic or inorganic acid and isolating the resulting salt. Typical salts include hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, and mesylate. Steady state: A state in which the amount of drug eliminated per unit time is equal to the amount of drug that reaches the systemic circulation per unit time. Summary of Multiple Embodiments This specification provides compositions comprising celecoxib and ciprofloxacin or a pharmaceutically acceptable salt of ciprofloxacin. For example, compositions are