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JP-2026514408-A - A novel integrated analytical platform for the quality assessment of complex natural products.

JP2026514408AJP 2026514408 AJP2026514408 AJP 2026514408AJP-2026514408-A

Abstract

The present invention provides a novel, integrated platform that enables the verification of manufacturing processes for complex natural products, as well as the standardization and evaluation of complex natural products. This platform allows for the "system-wide" characterization of complex mixtures contained in therapeutic and/or health-promoting products based on or composed of natural substances, without limiting the approach to reductionist chemical approaches targeting single markers. This is achieved through the integration of qualitative and quantitative fingerprint characterization data (metabolomics) and physical and biophysical activity data for the mixtures, thereby providing a product characterization that forms the basis for verifying manufacturing processes that can ensure the reproducibility of efficacy and safety across different batches of the product. The analytical platform described herein enables the assurance of a complex natural product as a whole, by considering all the characteristics of its quality and efficacy, through a multidimensional analytical approach, in order to ensure reproducibility regarding efficacy and safety. [Selection Diagram] None

Inventors

  • メルカティ，ヴァレンティナ
  • ジョヴァニョーニ，エミリアーノ
  • ジャンニ，マッティア
  • ブリコ，ミケーラ
  • マットリ，ルイーザ
  • メルカティ，ヴァレンティノ

Assignees

  • アボカ エス．ピー．エー．ソシエタ アグリコーラ

Dates

Publication Date
20260511
Application Date
20240327
Priority Date
20230328

Claims (10)

  1. A method for evaluating the properties of a product having therapeutic and/or health-promoting properties, wherein the product comprises a complex natural system, and the method is: a. A step of performing qualitative and quantitative fingerprint analysis of a standard formulation of the said product and a formulation different from the said standard formulation, wherein the difference from the standard formulation is due to the presence of the same component of the same quality in different proportions, or the presence of the same component of different quality in the same proportions, thereby obtaining a block, b. A step of analyzing one or more biophysical properties of a standard formulation of the product and a formulation different from the standard formulation, wherein the difference from the standard formulation is due to the presence of the same component of the same quality in different proportions, or the presence of the same component of different quality in the same proportions, thereby obtaining block Y of biophysical property data. c. A step of integrating data by correlation using multivariate analysis, which involves the correlation between data block X and data block Y, integrated by the correlation between each data obtained in a. and each data obtained in b., thereby obtaining a regression line for each pair of values, calculating the regression coefficient R² and mean squared error RMSEE, and selecting data pairs for which R² ≥ 0.8, thereby providing a model that enables the prediction of the respective biophysical properties of standard formulations from the fingerprints used, The method, including the method described above.
  2. A method for verifying the manufacture of one or more batches of products having therapeutic and/or health properties, including complex natural systems, the method being: a. A step of performing qualitative and quantitative fingerprint analysis of a standard formulation of the said product and a formulation different from the said standard formulation, wherein the difference from the standard formulation is due to the presence of the same component of the same quality in different proportions, or the presence of the same component of different quality in the same proportions, thereby obtaining X blocks of fingerprint data, b. A step of analyzing one or more biophysical properties of a standard formulation of the product and a formulation different from the standard formulation, wherein the difference from the standard formulation is due to the presence of the same component of the same quality in different proportions, or the presence of the same component of different quality in the same proportions, thereby obtaining a Y block of biophysical property data. c. A step of performing data integration by correlation using multivariate analysis, which involves the correlation between data block X and data block Y, integrated by the correlation between each data obtained in a. and each data obtained in b., thereby obtaining a regression line for each pair of values, calculating the regression coefficient R² and mean squared error RMSEE, and selecting data pairs for which R² ≥ 0.8, thereby providing a model that enables the prediction of the respective biophysical properties of standard formulations from the fingerprints used, To predict the biophysical properties described in db, the regression model developed in c. is used, and qualitative and quantitative fingerprint analysis is performed on one or more batches of the product to be validated using the same method as used in a. The method, including the method described above.
  3. The method according to claim 1 or 2, wherein the qualitative and quantitative fingerprint analysis is performed by recording NIR spectra, recording IR spectra, or by acquiring chromatograms from a chromatography system coupled to a mass spectrometer (e.g., gas chromatography, liquid chromatography, and qToF, single quadrupole, triple quadrupole, ion trap), or by mass spectrometry by direct injection into the mass spectrometer, similarly by chromatography systems, NMR coupled to liquid chromatography, UV-Vis spectroscopy.
  4. The method according to any one of claims 1 to 3, wherein one or more of the aforementioned biophysical properties are selected from mucosal adhesion properties, barrier effect, antioxidant effect, neutralizing activity, moisturizing properties, and lubricity.
  5. The method according to any one of claims 1 to 4, wherein the integration and correlation in item c are performed using PLS, OPLS, or PLS2.
  6. The method according to any one of claims 1 to 5, wherein the product having therapeutic properties, including a complex natural system, takes the form of a medical device composed of natural substances, and the product having health properties takes the form of a nutritional supplement composed of natural substances.
  7. The method according to any one of claims 1 to 6, wherein the natural substance is selected from a part of a plant, a powder of such a part, an extract of a plant or a part thereof (such as leaves, flowers, roots, bark, stems, seeds, fruits, petioles, or parts of flowers), a fraction of such an extract, essential oils, natural gums, natural resins, minerals, honey, propolis, animal products, and mineral products.
  8. The method according to any one of claims 1 to 7, wherein the product takes the form of a syrup, tablet, capsule, lozenge, granule, powder, solution, suspension, aerosol, aerosol powder, powder sachet, granule sachet, operol column, spray, cream, emulsion, soft gelatin capsule, or hard gelatin capsule.
  9. The method according to any one of claims 1 to 8, wherein R2 is ≥ 0.9.
  10. The method according to any one of claims 1 to 9, wherein the integration by correlation of the data in item c is performed using OPLS.

Description

Technical Field of the Invention The present invention relates to the verification, standardization, and evaluation of the manufacturing processes of complex natural products. In particular, the present invention provides a novel integrated platform that enables the verification, standardization, and evaluation of complex natural products, the platform which enables the characterization of complex mixtures based on or composed of natural substances, used in the manufacture of therapeutic products (e.g., medical devices) or products that support the physiological functions of organisms (e.g., dietary supplements), as a “whole system,” and this characterization is not limited to a chemical approach targeting a single marker. The platform enables the integration of qualitative and quantitative fingerprint characterization data metabolomics of the mixture with physical and biophysical activity data, thereby providing product characterization that forms the basis for a process of verifying manufacturing processes that can ensure reproducibility of efficacy and safety between different batches of the product. The analytical platform described herein enables the holistic assurance of the quality of complex natural products by considering their entirety, in order to guarantee reproducibility regarding efficacy and safety through a multidimensional analytical approach. Conventional Technology In recent years, complex natural product families have become increasingly important for certain patient groups (such as children and the elderly) in the treatment of so-called "self-limiting (spontaneously healing) diseases" (e.g., cough, sore throat, constipation), and also for important "still unmet medical needs," particularly for syndromes and functional disorders where classical pharmacological approaches cannot provide satisfactory answers in terms of risk-benefit ratios. This last parameter, which plays a crucial role in characterizing treatments, has gradually progressed in recent years, moving from evaluations focused solely on patients to also assessing the impact of treatments on the environment. This is because the introduction of non-biodegradable substances into the environment can cause direct and undeniable adverse effects on human health, creating an unsustainable vicious cycle. In this new relationship—which can be defined as a "risk-benefit relationship extended to the relationship between humans and the environment"—the use of natural products that are biodegradable by definition clearly presents an opportunity to consider all of their potential benefits. Regulation 2017/745 concerning medical devices, which stipulates the possibility of using complex natural products, in particular, for the treatment and prevention of medical conditions, establishes a clear regulatory framework that is added to the existing regulatory framework for pharmaceuticals. The fundamental difference between these two regulatory situations relates to the mechanism of action that achieves therapeutic activity: in the case of pharmaceuticals, this therapeutic activity is obtained through pharmacological (or immunological, or metabolic) action resulting from the interaction of a specific substance with a cellular target (usually a receptor), whereas in the case of medical devices, the therapeutic purpose must be achieved by a mechanism of action other than those mentioned above. Therefore, in accordance with this decree, therapeutic compositions/formulations are defined as either pharmaceuticals or medical devices based on the mechanism of action by which they exert their therapeutic effect. In the case of natural substances that have therapeutic effects, these substances can be classified as either pharmaceuticals or medical devices. However, in the case of pharmaceuticals, it is necessary to demonstrate that their therapeutic activity is achieved through specific substances contained in natural materials (generally defined as markers or active ingredients) that act on specific cellular targets. On the other hand, in the case of medical devices, therapeutic activity is related to the entire complex matrix and cannot be traced back to a specific mechanism of action. From a technical and regulatory standpoint, the above means that pharmaceuticals must have the ability to restore, modify, or alter physiological functions, considering that they achieve therapeutic effects through pharmacological, immunological, or metabolic mechanisms of action, either by a single molecule or a combination of molecules (Directive 2001/83, Article 2), whereas medical devices must function through non-pharmacological, immunological, or metabolic actions, thereby altering physiological or pathological processes or conditions (Regulation 2017/745, Article 2) [Capone, L., Geraci, A., Giovagnoni, E., Marcoaldi, R., and Palazzino, G. (2012) “Elementi di valutazione e di discernimento tra dispositivo medico e medicinale. Roma: Istituto Superiore di Sanita. Rappo