N for maintaining and / or improving bone health 1 - dihydrocaffeoyl-N 10 - compositions of caffeoyl spermidine

Abstract

Described herein are compositions for maintaining and / or improving bone health in a subject (e.g., an aging subject) comprising N 1 - dihydrocaffeoyl-N 10 - caffeoyl spermidine and an additive. Further, described herein are methods for maintaining and / or improving bone health in a subject (e.g., an aging subject). Further, described herein are methods for preventing and / or treating bone disease in a subject (e.g., an aging subject).

Description

Background Technology

[0001] This application relates to compositions of compounds, and their use for maintaining and / or improving bone health, and / or for treating and / or preventing bone diseases in subjects (e.g., aging subjects).

[0002] Spermine is the most abundant polyamine in most diverse human tissues. Produced from amino acid metabolism, spermine includes important cellular functions, including regulating cell growth, proliferation, tissue regeneration, DNA and RNA stabilization, enzymatic regulation, translational regulation, and autophagy. Furthermore, spermine exhibits anti-inflammatory and antioxidant properties, enhances mitochondrial metabolic function and respiration, promotes chaperone activity, and improves protein homeostasis. Intracellular spermine concentrations decrease during normal aging processes. Conversely, spermine administration has been associated with increased survival rates of immune cells in yeast, worms, flies, and humans, and reduced age-related mortality in mice. Very high spermine concentrations in semen can prevent cellular senescence and confer long-term survival on germline cells. Spermine homeostasis is influenced by nutrient absorption, intestinal origin, endogenous biosynthesis, degradation, and active transport systems between compartments.

[0003] Many of spermidine's anti-aging properties are causally related to its ability to ensure protein homeostasis by stimulating protective macroautophagy. Speridine induces autophagy by inhibiting several acetyltransferases. The optimal concentration of spermidine for maintaining healthy aging through optimal autophagy in humans is a subject of ongoing research. Age-related decline in spermidine may involve alterations in one or more different factors that determine its systemic bioavailability. The bioavailability of spermidine is determined by different sources of this polyamine: (i) cellular biosynthesis, (ii) production by gut microbiota, and (iii) nutrient supply, as well as (iv) catabolism and (v) urinary excretion.

[0004] Black goji berry (Lycium ruthenicum) is a flowering plant, commonly known as "Russian boxthorn." It belongs to the Solanaceae family (Solanaceae Juss) and is distributed in Central Asia, southern Russia, northwestern China, northern India, and Pakistan. Black goji berries grow in the Nubra Valley of India, as well as in salt deserts, sandy areas, and roadsides at altitudes of 400-3000 meters in Central Asia and northwestern China. Black goji berry extract is a source of spermidine.

[0005] Bone diseases, including osteoporosis, Paget's disease, osteogenesis imperfecta, rickets, osteomalacia, renal osteodystrophy, and hyperparathyroidism, remain a major public health problem in this country. These diseases cause approximately 1.5 million fractures each year, inflicting enormous physical and emotional costs on those affected and their families. They constitute a significant economic burden on individuals and society as a whole. Many of these costs are preventable because much has been learned about how to effectively prevent, diagnose, and treat bone diseases throughout life. However, due to a lack of awareness about the problem and the failure to apply existing knowledge, many measures that could alleviate this burden are not being implemented today. In fact, much of the public and even society considers osteoporosis a natural consequence of aging and something that cannot be changed.

[0006] Osteoporosis is a systemic skeletal disorder characterized by low bone mass and a deterioration in the microstructure of bone tissue, leading to more porous bone and an increased risk of fractures. It is the most common cause of bone fractures in older adults. Commonly fractured bones include the vertebrae in the spine, the forearm bones, the wrist bones, and the hip bones. Until a fracture occurs, there are usually no symptoms. Bone can become so brittle that it can break under minor pressure or spontaneously. After a fracture heals, some people may experience chronic pain and a decreased ability to perform normal activities.

[0007] Osteoporosis is caused by a decrease in maximum bone mass compared to normal, while bone loss is greater than normal. Postmenopausal bone loss increases due to decreased estrogen levels, while postmenopausal bone loss increases due to decreased testosterone levels, known as "male menopause." Osteoporosis can also be caused by many diseases or treatments, including alcoholism, anorexia, hyperthyroidism, kidney disease, and surgical removal of the oophores. Certain medications can increase the rate of bone loss, including some antiepileptic drugs, chemotherapy, proton pump inhibitors, selective serotonin reuptake inhibitors, and glucocorticoids. Smoking and lack of physical activity are also risk factors. Osteoporosis is defined as a bone mineral density that is 2.5 standard deviations lower than that of a younger adult. This is usually measured by dual-energy X-ray absorptiometry (DXA or DEXA) ("Prevention and management of osteoporosis," World Health Organization Technical Report Series, World Health Organization, Vol. 921, pp. 1–164 (2003)).

[0008] While osteoporosis can be defined as low bone mass that leads to structural fragility, it is difficult to determine the extent of the condition described by these qualitative terms. Using the World Health Organization's quantitative definition based on bone mineral density measurements, approximately 10 million Americans over the age of 50 have osteoporosis, and an additional 34 million have low bone mass or "osteopenia" in the hip, putting them at risk of osteoporosis, fractures, and potential complications later in life (National Osteoporosis Foundation. America's Bone Health: The State of Osteoporosis and Low Bone Mass in Our Nation. Washington, DC: National Osteoporosis Foundation (2002)).

[0009] If left unchecked, the bone health of Americans will only worsen, largely due to an aging population. In fact, unless the underlying bone health of Americans is significantly improved, the prevalence of osteoporosis and osteoporosis-related fractures will increase significantly. While little is known about the prevalence and treatment of other bone diseases, they can also have serious impacts on the health and well-being of those who suffer from them, especially if these bone diseases are not diagnosed and treated in a timely manner.

[0010] While aging cannot be prevented, treatment can reduce the degree of deformities and pain caused by osteoporosis. Further research into osteoporosis may lead to additional improvements in the treatment of these bone diseases and may even provide profound insights into how to prevent them.

[0011] Osteoporosis has no symptoms, and people are often unaware they have it until a bone breaks. Osteoporotic fractures occur in situations that healthy people would not normally break; therefore, osteoporotic fractures are considered fragility fractures. Examples of situations that people would not normally break include falling from standing height, normal daily activities such as lifting heavy objects, bending over, or coughing.

[0012] Besides increased fragility and the risk of fractures, osteoporosis can lead to other complications. Fractures caused by osteoporosis can result in disability in older adults and increase the risk of death following injury. Osteoporosis reduces quality of life, increases disability rates, and adds to the financial burden on the healthcare system.

[0013] Proper nutrition and physical exercise, including exercise programs for older adults, physical therapy, and hormone therapy, have been used to prevent osteoporosis and improve bone health.

[0014] Nevertheless, there remains a need for compositions and methods for improving bone health. Compositions containing dicaffeoylspermine derivatives for improving bone health will make a useful contribution to the field. Summary of the Invention

[0015] In the embodiments, this document describes a composition for improving bone health in subjects, which comprises N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine and additives. Compared to subjects who did not receive the composition, the composition maintains and / or improves bone health in subjects who received the composition by: increasing bone volume fraction (BVF), increasing trabecular thickness (Tb.Th), reducing trabecular separation (Tb.Sp), increasing trabecular number (Tb.N), increasing bone mineral density (BMD), increasing bone mineral content (BMC); and / or increasing bone surface density (BS / TV expression). Subjects were aged subjects. The composition increases spermidine content in subjects within 1 hour after administration. The composition may contain at least 10% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine, or at least 25% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine, or at least 45% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylspermine. The composition is formulated for oral administration, wherein N 1 -Dihydrocaffeoyl-N 10 - The dosage of caffeoyl spermidine ranges from 1.5 mg to 50 mg per kilogram of subject body weight. The composition may be in the form of tablets, ready-to-drink beverages, concentrates, powders, granules, gels, solids, semi-solids, frozen liquids, lozenges, hard candies, dissolving strips, and chewing gum. The composition may be a nutritional supplement.

[0016] Another implementation involves N 1 -Dihydrocaffeoyl-N 10 - Use of a composition of caffeoyl spermidine and additives to improve bone health in subjects.

[0017] Another implementation involves a method for maintaining and / or improving bone health in aging subjects, comprising administering to the subject an effective amount containing N 1 -Dihydrocaffeoyl-N 10- A composition of caffeoyl spermidine and additives. Compared to aging subjects who have not received this composition, the composition maintains and / or improves bone health in aging subjects by: increasing bone volume fraction (BVF), increasing trabecular thickness (Tb.Th), reducing trabecular separation (Tb.Sp), increasing trabecular number (Tb.N), increasing bone mineral density (BMD), increasing bone mineral content (BMC); and / or increasing bone surface area density (BS / TV) expression. The composition increases spermidine levels in subjects within 1 hour of administration. The composition contains at least 10% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine, or at least 25% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine, or at least 45% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylspermine. The composition is for oral administration, wherein N 1 -Dihydrocaffeoyl-N 10 The dosage of caffeoyl spermidine ranges from 1.5 mg to 50 mg per kilogram of subject body weight.

[0018] Another implementation involves a method for preventing and / or treating bone diseases in subjects, comprising administering to the subject an effective amount containing N 1 -Dihydrocaffeoyl-N 10 - A composition of caffeoyl spermidine and additives. Bone diseases include osteoporosis, Paget's disease, osteogenesis imperfecta, rickets, osteomalacia, renal osteodystrophy, or hyperparathyroidism. The composition contains at least 10% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine, or at least 25% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine, or at least 45% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylspermine. This composition is for oral administration, wherein N 1 -Dihydrocaffeoyl-N 10 The dosage of caffeoyl spermidine ranges from 1.5 mg to 50 mg per kilogram of subject body weight. This composition is a nutritional supplement.

[0019] Further areas of application will become apparent from the description provided herein. It should be understood that these descriptions and specific examples are intended for illustrative purposes only and are not intended to limit the scope of this disclosure. Attached Figure Description

[0020] To facilitate a good understanding of this disclosure, various forms of the disclosure will now be described by way of example with reference to the accompanying drawings. Components in the drawings are not necessarily drawn to scale. Furthermore, in the drawings, similar reference numerals denote corresponding parts in different views.

[0021] Figure 1 N is shown 1 -Dihydrocaffeoyl-N 10 The structure of -caffeoyl spermidine.

[0022] Figure 2 The SAMP8 media set and N were depicted. 1 -Dihydrocaffeoyl-N 10 Images of bone in the caffeoyl spermidine treatment group: (a) image of cortical bone, (b) image of trabecular bone, (c) fusion of cortical bone and trabecular bone, and (d) image of bone.

[0023] Figure 3 Charts depicting bone analysis are shown: (a) bone volume fraction (BV / TV), (b) trabecular thickness (Tb.Th), (c) trabecular separation (Tb.Sp), (d) trabecular number (Tb.N), (e) bone mineral density (BMD), (f) bone mineral content (BMC), and (g) bone surface area density (BS / TV). Values ​​are expressed as mean ± SE. * indicates p < 0.05 compared to the SAMP8 group. ** indicates p < 0.001 compared to the SAMP8 group.

[0024] Detailed description of the accompanying drawings and the current preferred embodiments

[0025] The invention will now be described more fully. For the purposes of the following detailed description, it should be understood that various alternative variations and sequences of steps may be assumed in the invention, unless otherwise expressly stated to the contrary. Therefore, before describing the invention in detail, it should be understood that the invention is not limited to the specific exemplified embodiments, which may of course be varied. The following description is merely exemplary in nature and is not intended to limit this disclosure, its application, or its uses.

[0026] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Such terms as defined in commonly used dictionaries should be interpreted as having the same meaning as in the context of the relevant field.

[0027] definition

[0028] In the context of describing this disclosure (particularly in the context of the appended claims), the terms “a,” “an,” and “the,” and similar designations, shall be construed as covering both singular and plural forms, unless otherwise stated herein or clearly contradicted by the context. The term “a plurality” is used by the applicant in its broadest sense, in lieu of any other implied definition or limitation above or below, unless the applicant expressly states otherwise, it refers to a quantity of more than one. Unless otherwise stated herein, the enumeration of numerical ranges herein is intended only as a shorthand method for individually referring to each individual value falling within that range, and each individual value is incorporated into the specification as if it were individually enumerated herein. All methods described herein may be performed in any suitable order, unless otherwise indicated herein or clearly contradicted by the context.

[0029] The terms "preferred" and "ideally" refer to embodiments of the invention that provide certain benefits under specific circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, listing one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of the invention.

[0030] As used herein, “about,” “approximately,” or “roughly” generally means within 20%, preferably within 10%, and more preferably within 5% of a given value or range. The numerical quantities given herein are approximate; this means that the terms “about,” “approximately,” or “roughly” can be inferred unless explicitly stated otherwise. When the term “about” is used at the endpoints of a value or range, it should be understood that this disclosure includes both the specific value and the endpoint referred to.

[0031] As used herein, the terms “comprise(s)”, “include(s)”, “having”, “has”, “can”, “contain(s)”, and variations thereof are intended as open-ended transitional phrases, terms, or words that do not exclude the possibility of other behaviors or structures. Whether explicitly stated or not, this specification also covers other instances of “comprises the following,” “consists of the following,” and “substantially consists of the following”: instances or elements presented herein.

[0032] In describing the elements of this disclosure, the terms 1, 2, first, second, A, B, (a), (b), etc., may be used herein. These terms are used only to distinguish one element from another, but do not limit the corresponding element, regardless of the nature or order of the corresponding element.

[0033] This article uses the term "composition" to describe a composition containing at least N 1 -Dihydrocaffeoyl-N10 - Formulations of caffeoyl spermidine. This term refers to edible formulations that may be suitable for oral ingestion by subjects (e.g., aging human subjects). Exemplary compositions include, but are not limited to: sprays (e.g., aerosols), powders, chewing gum, ingestible solids, gels, aqueous beverages, dry powders (e.g., powders that are directly edible or can be reconstituted with liquid to provide a beverage as defined herein), nutrition bars, lozenges, tablets, capsules, rice paper wafers, pastes, etc. Other compositions are described herein. In some preferred embodiments, the compositions described herein are in tablet form.

[0034] As used in this article, the term "N" 1 -Dihydrocaffeoyl-N 10 "-Caffeoyl spermidine" or "DHCS" refers to a compound found in black goji berry fruit, which has Chemical Abstracts Service ("CAS") registration number 121850-61-1, C 25 H 33 The molecular formula and the following structural formula of N3O6:

[0035]

[0036] N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsperidinine can also be called "N 1 - Hydrocaffeoyl-N 10 -Caffeoylsemidine.

[0037] In one example, the composition may contain at least about 0.5% by weight of N. 1 -Dihydrocaffeoyl-N 10-Caffeoyl spermidine, or at least about 1.0% by weight, or at least about 1.5% by weight, or at least about 2.0% by weight, or at least about 2.5% by weight, or at least about 3.0% by weight, or at least about 3.5% by weight, or at least about 4.0% by weight, or at least about 4.5% by weight, or at least about 5.0% by weight, or at least about 5.5% by weight, or at least about 6.0% by weight, or at least about 6.5% by weight, or at least about 7.0% by weight, or at least about 7.5% by weight, or at least about 8.0% by weight, or at least about 8.5% by weight, or At least about 9.0% by weight, or at least about 9.5% by weight, or at least about 10.0% by weight, or at least about 10.5% by weight, or at least about 11.0% by weight, or at least about 11.5% by weight, or at least about 12.0% by weight, or at least about 12.5% ​​by weight, or at least about 13.0% by weight, or at least about 13.5% by weight, or at least about 14.0% by weight, or at least about 14.5% by weight, or at least about 15.0% by weight, or at least about 15.5% by weight, or at least about 16.0% by weight, or at least about 16.5% by weight. %, or at least about 17.0% by weight, or at least about 17.5% by weight, or at least about 18.0% by weight, or at least about 18.5% by weight, or at least about 19.0% by weight, or at least about 19.5% by weight, or at least about 20.0% by weight, or at least about 20.5% by weight, or at least about 21.0% by weight, or at least about 21.5% by weight, or at least about 22.0% by weight, or at least about 22.5% by weight, or at least about 23.0% by weight, or at least about 23.5% by weight, or at least about 24.0% by weight, or at least about 24.5% by weight, or at least about 25.0% by weight, or at least about 25.5% by weight, or at least about 26.0% by weight, or at least about 26.5% by weight, or at least about 27.0% by weight, or at least about 27.5% by weight, or at least about 28.0% by weight, or at least about 28.5% by weight, or at least about 29.0% by weight, at least about 29.5% by weight, at least about 30.0% by weight, at least about 35.0% by weight, at least about 40.0% by weight, at least about 45.0% by weight, or at least about 50.0% by weight, or more. In some embodiments, N 1 -Dihydrocaffeoyl-N 10 The dosage of caffeoyl spermidine can range from 1.5 mg to 50 mg per kilogram of body weight. In some other embodiments, N 1 -Dihydrocaffeoyl-N 10- The dosage of caffeoyl spermidine can be at least 1.5 mg / kg body weight; at least 2 mg / kg body weight; at least 3 mg / kg body weight; at least 4 mg / kg body weight; at least 5 mg / kg body weight; at least 6 mg / kg body weight; at least 7 mg / kg body weight; at least 8 mg / kg body weight; at least 9 mg / kg body weight; at least 10 mg / kg body weight; at least 11 mg / kg body weight; at least 12 mg / kg body weight; at least 13 mg / kg body weight; at least 14 mg / kg body weight; at least 15 mg / kg body weight; at least 16 mg / kg body weight; at least 17 mg / kg body weight; at least 18 mg / kg body weight; at least 19 mg / kg body weight; at least 20 mg / kg body weight; at least 21 mg / kg body weight; at least 22 mg / kg body weight; at least 23 mg / kg body weight; at least 24 mg / kg body weight; at least 25 mg / kg body weight; at least 16 mg / kg body weight; at least 27 mg / kg body weight. mg; at least 28 mg per kilogram of body weight; at least 29 mg per kilogram of body weight; at least 30 mg per kilogram of body weight; at least 31 mg per kilogram of body weight; at least 32 mg per kilogram of body weight; at least 33 mg per kilogram of body weight; at least 34 mg per kilogram of body weight; at least 35 mg per kilogram of body weight; at least 36 mg per kilogram of body weight; at least 37 mg per kilogram of body weight; at least 38 mg per kilogram of body weight; at least 39 mg per kilogram of body weight; at least 40 mg per kilogram of body weight; at least 41 mg per kilogram of body weight; at least 42 mg per kilogram of body weight; at least 43 mg per kilogram of body weight; at least 44 mg per kilogram of body weight; at least 45 mg per kilogram of body weight; at least 46 mg per kilogram of body weight; at least 47 mg per kilogram of body weight; at least 48 mg per kilogram of body weight; at least 49 mg per kilogram of body weight; or at least 50 mg per kilogram of body weight; or more. In some preferred embodiments, the dose is 30 mg per kilogram of body weight.

[0038] As used herein, the term "effective amount" or "pharmaceutical or therapeutically effective amount" refers to the amount of an active ingredient or extract administered orally to a subject to trigger the desired effect (e.g., maintain and / or improve bone health) without causing or minimizing adverse toxicity in the subject, and / or without any undesirable side effects. Those skilled in the art will recognize that effective amounts can vary from person to person due to external factors such as age, sex, disease state, race, weight, formulation of the composition, availability of other active ingredients in the formulation, etc. For example, as shown in the examples below, N 1 -Dihydrocaffeoyl-N 10 -The effective ratio of caffeoyl spermidine to mouse feed is 25 mg N 1 -Dihydrocaffeoyl-N 10- Caffeoyl spermidine is mixed in 1 kg of mouse feed (0.25 g / kg).

[0039] The term "bone health" refers to the strength and condition of the skeletal system in a subject (e.g., an aging subject), which is crucial for mobility, fracture prevention, and overall well-being. Healthy bones are dense and strong, composed of constantly renewing living tissue. Healthy bones provide the framework for the body, enabling movement and protecting it from injury. Bones act as a reservoir of minerals, essential for the function of many other life-sustaining systems in the body. However, unhealthy bones perform poorly in performing these functions and can lead to debilitating fractures. As we age, bones naturally become more fragile and less dense. Women have less bone tissue than men and are at greater risk of osteoporosis.

[0040] In N 1 -Dihydrocaffeoyl-N 10 In the context of the effects of caffeoyl spermidine on bone health, the terms "improved," "improving," and "improved" refer to improvements in the treatment group (i.e., the group receiving the described N-containing substance) compared to the "carrier group" or "blank group." 1 -Dihydrocaffeoyl-N 10 The composition of -caffeoyl spermidine (group) was statistically significant, and the statistical results showed P values ​​<0.001 or <0.05 compared with the blank group. For example, as shown in this article, compared with the "blank group" (e.g., SAMP8 mice), N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine treatment group (e.g., administration of N 1 -Dihydrocaffeoyl-N 10 SAMP8 mice containing caffeoyl spermidine showed significantly increased bone volume fraction (BVF), significantly increased trabecular thickness (Tb.Th), significantly decreased trabecular separation (Tb.Sp), significantly increased trabecular number (Tb.N), significantly increased bone mineral density (BMD), significantly increased bone mineral content (BMC); and / or significantly increased bone surface area density (BS / TV) expression. Figure 3 ).

[0041] In N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsperidin (e.g., N-acetyl) 1 -Dihydrocaffeoyl-N 10In the context of the effects of caffeoyl spermidine on bone in SAMP8 mice, the terms "increasing" and "increased" refer to the increase in bone density compared to the "carrier group" or "blank group" (e.g., SAMP8 mice), using the described N-containing... 1 -Dihydrocaffeoyl-N 10 Treatment with the combination of caffeoyl spermidine resulted in a statistically significant increase in the studied bone health indicators (i.e., bone volume fraction, trabecular thickness, trabecular number, bone mineral density, bone mineral content, and bone surface area density), with statistical results P < 0.05 or < 0.001.

[0042] In N 1 -Dihydrocaffeoyl-N 10 In the context of the effects of caffeoyl spermidine on bone, the terms "decreasing" or "decreased" refer to a reduction in bone density compared to the "carrier group" or "blank group," using the described N-containing... 1 -Dihydrocaffeoyl-N 10 Treatment with the combination of caffeoyl spermidine resulted in a statistically significant reduction in the studied bone health indicators (e.g., trabecular separation), with a statistical result P < 0.05.

[0043] The term "additive" refers to a substance added to a formulation along with a therapeutic agent to impart specific qualities to the formulation. Additives have little therapeutic value but are essential in the manufacture of various dosage forms. Additives include excipients and carriers.

[0044] The term "excipient" refers to any substance that contributes to the absorption of a composition, stabilizes the composition, or contributes to the preparation of the composition. Therefore, excipients can have functions such as keeping the ingredients bound together (e.g., starch, sugar, or cellulose), sweetening functions, coloring functions, protecting the drug from external media (e.g., isolating it from air and / or moisture), filling functions in tablets, capsules, or any other form of formulation (e.g., dicalcium phosphate), disintegration functions that promote the dissolution of the ingredient and its absorption in the intestine, without excluding other types of excipients not mentioned in this paragraph. Therefore, the term "excipient" is defined as a substance contained in a dosage form that is added to an active substance or combination thereof to enable its preparation and stabilization, alter its sensory properties, or determine the physical / chemical properties of a pharmaceutical composition and its bioavailability. "Pharmaceutically acceptable" excipients should not interact with the activity of the active compound in the described composition. Examples of excipients are binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavorings, and colorings. More specifically, non-limiting examples of acceptable excipients include starch, sugar, xylitol, sorbitol, calcium phosphate, steroidal fats, talc, silicon dioxide, or glycerol.

[0045] “Administering” and “administration” refer to the method of delivery. Daily doses can be divided into one, two, three or more doses in a suitable form to be administered once, twice, three or more times over a period of time (e.g., one day, one week, one month).

[0046] "Treatment," "improvement," or "relief" means the administration of a composition for therapeutic purposes or the administration of treatment to a subject with an existing disorder to improve the subject's condition. Such improvement or treatment is at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% compared to an equivalent untreated control, as measured by any standard, suitable technique.

[0047] As described herein, the term "subject" is equivalent to the terms "individual" and "patient," and these terms are used interchangeably. "Subject" refers to any animal of any kind. Examples of subjects include, but are not limited to, commercially raised animals such as birds (hens, ostriches, chickens, geese, partridges, etc.), rabbits, hares, domesticated animals (dogs, cats, etc.), livestock (e.g., sheep and goats, pigs, wild boars, horses, ponies, etc.), and cattle (bulls, steers, etc.). In certain embodiments, the subject is a mammal, preferably a primate, and more preferably a human of any race, sex, or age. In some preferred embodiments, the subject is an elderly subject.

[0048] The term "aging subject" refers to a subject who exhibits a time-related decline in physiological functions essential for survival and reproduction. The age at which aging begins varies and depends on a variety of factors, including genetics, lifestyle, and environment. For example, in humans, the first signs of aging become apparent on the skin surface around age 25; muscle strength and endurance typically peak around age 35 and then gradually decline. In human subjects, bone begins to age around age 35, at which point bone breakdown begins to occur faster than bone replacement. Bone is thickest and strongest in early adulthood, up to around 28 or 29 years of age. From age 25 to around 50, bone density tends to remain stable. After age 50, bone breakdown exceeds bone formation (Osteoporosis: What You Need to Know as You Age | Johns Hopkins Medicine). The body continuously removes old bone and replaces it with new bone through a process called remodeling. By age 40, all the removed bone has been replaced. After age 40, less bone is replaced. In the context of this invention, the aged subject is a subject who is at least 35 years old; preferably, at least 40 years old; more preferably, at least 45 years old; and even more preferably, at least 50 years old.

[0049] Composition

[0050] In one embodiment, this document describes a composition for maintaining and / or improving bone health in subjects, the composition comprising N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine and additives.

[0051] In another embodiment, this document describes a composition for maintaining and / or improving bone health in aging subjects, the composition comprising N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine and additives.

[0052] In one embodiment, relative to a subject who has not been given the composition, the composition maintains and / or improves bone health in a subject (e.g., an aging subject) by at least one of the following: increasing bone volume fraction (BVF), increasing trabecular thickness (Tb.Th), reducing trabecular separation (Tb.Sp), increasing trabecular number (Tb.N), increasing bone mineral density (BMD), increasing bone mineral content (BMC), and / or increasing bone surface area density (BS / TV) expression.

[0053] In one embodiment, the described composition may contain at least 10% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine; or, at least 25% by weight N1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine; or, at least 45% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0054] In one embodiment, the composition can be formulated for oral administration.

[0055] In one instance, for oral administration, the described N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsperimidamine compositions can be formulated as ready-to-drink beverages, concentrates (e.g., syrups), dry compositions (e.g., powders, granules, or tablets that can be reconstituted with liquids (e.g., water), gels, solids, semi-solids (e.g., ice cream, pudding, or yogurt), frozen liquids (e.g., popsicles), tablets or hard candies, dissolving strips (e.g., edible strips containing pullulan and the compositions of the present invention), and chewing gum. Other known formulations are also covered.

[0056] In one instance, for oral administration, N 1 -Dihydrocaffeoyl-N 10 -Caffeoylspermine can be combined with one or more solid inactive ingredients to prepare tablets, capsules, pills, powders, granules, or other suitable solid dosage form compositions. For example, N 1 -Dihydrocaffeoyl-N 10 -Caffeoylspermine can be combined with at least one excipient selected from fillers, binders, humectants, disintegrants, dissolution inhibitors, absorption accelerators, wetting agents, absorbents, or lubricants. Other useful excipients may include magnesium stearate, calcium stearate, mannitol, xylitol, sweeteners, starch, carboxymethyl cellulose, microcrystalline cellulose, silica, gelatin, etc.

[0057] The term "formulation" may be intended to include N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine is formulated together with an encapsulating material as a carrier to provide a capsule in which the extract or compound (with or without another carrier) is surrounded by the carrier, which in turn reacts with N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine association.

[0058] The formulation contains N in powder or tablet form. 1 -Dihydrocaffeoyl-N 10In certain instances of caffeoyl spermidine, the powder or tablet may contain the following amounts of the extract or compound disclosed herein: from about 5% by weight, or from about 10% by weight, or from about 15% by weight, or from about 20% by weight, or from about 25% by weight, or from about 30% by weight, or from about 35% by weight, or from about 40% by weight, or from about 45% by weight, or from about 50% by weight, or from about 55% by weight, or from about 60% by weight, or from about 65% by weight to about 70% by weight; or from about 10% by weight to about 15% by weight, or from about 20% by weight, or from about 25% by weight, or from about 30% by weight, or from about 35% by weight, or from about 40% by weight, or from about 45% by weight, or from about 50% by weight, or from about 55% by weight, or from about 60% by weight, or from about 65% by weight, or from any of the aforementioned minimum or maximum values, including any subrange therebetween. In some embodiments, N 1 -Dihydrocaffeoyl-N 10 The dosage of caffeoyl spermidine can be in the range of 1.5 mg to 50 mg per kilogram of body weight or any subrange thereof.

[0059] Examples of suitable carriers include microcrystalline cellulose, sugars, lactose, pectin, dextrin, starch, gelatin, tragacanth gum, methylcellulose, sodium carboxymethyl cellulose, low-melting-point waxes, and cocoa butter. Examples of other excipients include magnesium stearate, stearic acid, talc, and silica.

[0060] In some instances, the composition may contain a binder. Examples of binders may include disaccharides, such as sucrose or lactose; polysaccharides and their derivatives, such as starch, cellulose, modified cellulose (e.g., microcrystalline cellulose or cellulose ethers, such as hydroxypropyl cellulose); sugar alcohols, such as xylitol, sorbitol, or mannitol; proteins, such as gelatin; and synthetic polymers, such as polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG).

[0061] In some instances, the composition may contain a humectant. Examples of humectants may include propylene glycol, hexanediol, butylene glycol, aloe vera gel, alpha-hydroxy acids (e.g., lactic acid), egg yolk or egg white, triacetin, honey, lithium chloride, molasses, polymeric polyols (e.g., polydextrose), soap bark, sodium hexametaphosphate E452i, urea, or castor oil.

[0062] In some instances, the composition may contain a disintegrant. Examples of disintegrants may include crosslinked polymers, such as croscarmellose (crospovidone) or croscarmellose sodium (croscarmellose sodium), or modified starch, such as sodium starch glycolate.

[0063] In some instances, the composition may contain a wetting agent. Examples of wetting agents may include benzalkonium chloride, benzyl chloride, cetylpyridine chloride, poloxamer 188, poloxamer 407, polyoxyethylene 40 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, sodium lauryl sulfate, sorbitan monooleate, or sorbitan monostearate.

[0064] In some instances, the composition may contain a lubricant. Examples of lubricants may include talc, silica, or fats, such as vegetable fats, magnesium stearate, or stearic acid.

[0065] In some instances, the composition may contain a sweetener. Examples of sweeteners may include sugar, corn syrup, aspartame, sucralose, acesulfame potassium, saccharin, or xylitol.

[0066] In one example, examples of liquid formulations of the described compositions may include compositions combined with a carrier, for example, in the form of a solution, suspension, or emulsion, wherein the carrier may be a fluid, such as a solvent or emulsifier. In some examples, the liquid formulation may be water or a water-propylene glycol solution. In other examples, parenteral liquid formulations may be formulated as solutions in aqueous polyethylene glycol solutions. Thus, the described compositions may be formulated for parenteral administration (e.g., by injection, such as bolus or continuous infusion) and may be present in unit doses or in ampoules, pre-filled syringes, small-volume infusions, or multi-dose containers with added preservatives. The compositions may be in the form of suspensions, solutions, or emulsions, for example, in oily or aqueous media, and may contain formulations such as suspending agents, stabilizers, and / or dispersants. Alternatively, the described compositions may be in powder form (obtained by aseptic separation of sterile solids or by lyophilization of solutions) for reconstitution with a suitable media (e.g., sterile, pyrogen-free water) prior to use.

[0067] In some instances, aqueous solutions suitable for oral use can be prepared by dissolving the described composition in water and adding appropriate colorants, flavorings, stabilizers, and thickeners as needed. Aqueous suspensions suitable for oral use can be prepared by dispersing finely crushed active ingredients with a viscous material (e.g., natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other well-known suspending agents) in water.

[0068] In some instances, the composition may contain an emulsifier, which is provided for combining two or more immiscible fluids in a single mixture and maintaining the stability of the mixture. Examples of emulsifiers may include gum arabic, carbomer copolymers, carbomer interpolymers, cholesterol, coconut oil, diethylene glycol stearate, ethylene glycol stearate, glyceryl distearate, glyceryl monolinoleate, glyceryl monooleate, glyceryl monostearate, lanolin alcohol, lecithin, monoglycerides and diglycerides, poloxamer, polyethylene oxide 50 stearate, polyethylene oxide 10 oleyl ether, polyethylene oxide 20 cetearyl ether, polyethylene oxide 35 castor oil, polyethylene oxide 40 hydrogenated castor oil, polyethylene oxide 40 stearate, polyethylene oxide dodecyl ether, polyethylene oxide octadecyl ether, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, propylene glycol monostearate, sodium cetearyl sulfate, sodium dodecyl sulfate, sodium stearate, dehydrated sorbitan monolaurate, and sorbitan monooleate. (monoleate), sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, stearic acid and waxes.

[0069] The formulation is preferably a unit dosage form. In this form, the formulation can be subdivided into unit doses containing appropriate amounts of the active ingredient. A unit dosage form can be a packaged formulation containing discrete amounts of the formulation, such as packaged tablets, capsules, and powders in vials or ampoules. Alternatively, a unit dosage form can be the capsule, tablet, sachets, or lozenges themselves, or a unit dosage form can be any appropriate quantity of such unit dosage forms in packaged form.

[0070] Further details regarding the formulation and application techniques can be found in the latest edition of Remington's Pharmaceutical Sciences (Mack Publishing Co., Easton, Pa.).

[0071] Form and Use

[0072] In one instance, the described composition can be used to improve bone health in a subject. The subject may be an aging subject.

[0073] In another instance, the described composition can be used to maintain bone health in a subject, who may be an aging subject.

[0074] Compared to aging subjects who did not receive the composition, the composition maintained and / or improved bone health in aging subjects by increasing bone volume fraction (BVF), increasing trabecular thickness (Tb.Th), reducing trabecular separation (Tb.Sp), increasing trabecular number (Tb.N), increasing bone mineral density (BMD), increasing bone mineral content (BMC); and / or increasing bone surface area density (BS / TV) expression.

[0075] In one example, suitable dosage forms for the described composition may include tablets, capsules, solutions, suspensions, powders, chewing gum, and confectionery. Examples of compositions may include supplements. Sublingual delivery systems may include, but are not limited to, sublingual and topical soluble tablets, drops, and beverages. Edible films, hydrophilic polymers, orally soluble films, or orally soluble strips may be used. Examples of compositions may include additives, such as excipients or carriers.

[0076] In yet another instance, the described composition can be used for oral administration.

[0077] In yet another embodiment, the described composition may be a tablet.

[0078] In yet another instance, the described composition can be used as a nutritional supplement.

[0079] method

[0080] In one instance, this disclosure provides a method for maintaining and / or improving bone health in a subject, comprising administering to the subject a substance containing N 1 -Dihydrocaffeoyl-N 10 A composition of caffeoyl spermidine. The subject may be an aging subject. Compared to aging subjects who have not received the composition, the composition maintains and / or improves bone health in aging subjects by: increasing bone volume fraction (BVF), increasing trabecular thickness (Tb.Th), reducing trabecular separation (Tb.Sp), increasing trabecular number (Tb.N), increasing bone mineral density (BMD), increasing bone mineral content (BMC); and / or increasing bone surface area density (BS / TV) expression. The composition increases spermidine content in subjects within 1 hour after application. The composition contains at least 10% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine; or, the composition contains at least 25% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine; or, the composition contains at least 45% by weight N 1 -Dihydrocaffeoyl-N 10-Caffeoylspermine. This composition can be administered orally.

[0081] In another embodiment, this disclosure provides a method for preventing and / or treating bone diseases in a subject, comprising administering to the subject an effective amount containing N 1 -Dihydrocaffeoyl-N 10 - A composition of caffeoyl spermidine and additives. Bone diseases may include osteoporosis, Paget's disease, osteogenesis imperfecta, rickets, osteomalacia, renal osteodystrophy, or hyperparathyroidism. The composition contains at least 10% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine; or, the composition contains at least 25% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine; or, the composition contains at least 45% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylspermidine. This composition can be taken orally. This composition can be a nutritional supplement.

[0082] In one instance, this disclosure provides a spermidine supplement comprising: i) selected from N 1 -Dihydrocaffeoyl-N 10 - Compounds of caffeoyl spermidine; and ii) additives. In some instances, the compounds can be at least partially hydrolyzed in vivo to provide spermidine.

[0083] The above compositions and methods can be better understood in conjunction with the following examples. Furthermore, the following non-limiting examples are illustrative. The methods shown are applicable to other embodiments of compositions of substances to be screened and evaluated according to this disclosure. The procedures described as general methods describe methods that are generally considered effective for screening and evaluating compositions of substances. However, those skilled in the art will understand that it may be necessary to modify the procedures of any given embodiment of this disclosure, for example, by changing the order or steps and / or the chemical reagents used. Example

[0084] SAMP8, a mouse strain prone to accelerated aging, is a mouse strain that exhibits phenotypes associated with accelerated aging. SAMP8 displays various age-related phenotypes, such as autonomic dysfunction and neurodegenerative disorders (Chikamoto, A., et al., “Early attenuation of autonomic nervous function in senescence-accelerated mouse-prone 8 (SAMP8),” Exp Anim., 68(4):511 (2019)) and sarcopenia (Guo, AY, et al., “Muscle mass, structural and functional investigations of senescence-accelerated mouse P8 (SAMP8),” Exp Anim., 64(4):425 (2015)). It is widely used for bone health assessment (Sanada, Y., et al., “Senescence-accelerated mice prone 8 (SAMP8) in male as a spontaneous osteoarthritis model,” Arthritis Res Ther., 24(1):235 (2022)).

[0085] Example 1: N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine improves bone health during aging

[0086] (1) Methods and Procedures

[0087] Using SAMP8 mice to study N 1 -Dihydrocaffeoyl-N 10 - The effects of caffeoyl spermidine on bone health. The SAMP8 mice used in this study had a lifespan of approximately 12-13 months. The experiment began with SAMP8 mice at 3 months of age and ended when the mice were 8 months old. SAMP8 mice were obtained from Beijing HFK Bioscience, China.

[0088] N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine was obtained from Laboratory Amway I&S, China.

[0089] SAMP8 mice were administered with or without N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine mouse feed.

[0090] N in mouse feed 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine is 25 mg N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine is mixed into 1 kg of mouse feed (0.25 g / kg).

[0091] At the end of the treatment period, histological and micro-computed tomography (mCT) scans were used to determine the difference between the results and those without N-125 treatment. 1 -Dihydrocaffeoyl-N 10 Compared to mice treated with -caffeoylsemine, mice treated with N 1 -Dihydrocaffeoyl-N 10 Changes in SAMP8 mice treated with caffeoyl spermidine (AA001).

[0092] (2) Results

[0093] Figure 2 The SAMP8 media set and N were displayed. 1 -Dihydrocaffeoyl-N 10 Images of bone in the caffeoyl spermidine treatment group: (a) image of cortical bone; (b) image of trabecular bone; (c) combined cortical bone and trabecular bone; (d) image of bone.

[0094] Compared with the control group, AA001 treatment increased trabecular bone density, cortical bone thickness, and overall bone structure integrity, demonstrating its effectiveness in improving skeletal health and stability in SAMP8 mice. The results were statistically significant.

[0095] like Figure 3 As shown, compared with SAMP8-mediated mice (without N... 1 -Dihydrocaffeoyl-N 10 Compared to SAMP8 mice treated with caffeoyl spermidine, SAMP8 mice were administered N... 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine increased bone volume fraction (BVF), increased trabecular thickness (Tb.Th), decreased trabecular separation (Tb.Sp), increased trabecular number (Tb.N), increased bone mineral density (BMD), increased bone mineral content (BMC), and increased bone surface area density (BS / TV). The results were statistically significant.

[0096] (3) Conclusion

[0097] These results indicate that the application of N 1 -Dihydrocaffeoyl-N 10- Caffeoyl spermidine (AA001) can effectively improve bone health in aging mice.

[0098] Furthermore, this study shows that N 1 -Dihydrocaffeoyl-N 10 -Caffeoyl spermidine can at least maintain and surprisingly improve bone health during aging.

[0099] In summary, research indicates that N, which can be found in black goji berries, 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine can maintain and / or improve bone health during aging.

[0100] Although this disclosure has been described with reference to embodiments and accompanying drawings, this disclosure is not limited thereto, but can be modified and changed by those skilled in the art without departing from the spirit and scope of this disclosure.

[0101] Among other things, the subject matter of this disclosure may also cover the following:

[0102] The first aspect relates to a composition for improving bone health in subjects, comprising N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine and additives.

[0103] The second aspect relates to the composition of aspect 1, wherein, relative to subjects who have not received the composition, the composition maintains and / or improves bone health in subjects who have received the composition by: increasing bone volume fraction (BVF), increasing trabecular thickness (Tb.Th), reducing trabecular separation (Tb.Sp), increasing trabecular number (Tb.N), increasing bone mineral density (BMD), increasing bone mineral content (BMC); and / or increasing bone surface area density (BS / TV) expression.

[0104] The third aspect involves the composition of aspect 1 or 2, wherein the subject is an aging subject.

[0105] The fourth aspect relates to the compositions of aspects 1 to 3, wherein the composition increases spermidine content in the subject within 1 hour after administration of the composition.

[0106] The fifth aspect relates to the compositions of aspects 1 to 4, which contain at least 10% by weight of N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0107] The sixth aspect relates to the compositions of aspects 1 to 4, which contain at least 25% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0108] The seventh aspect relates to the compositions of aspects 1 to 4, which contain at least 45% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0109] The eighth aspect relates to the compositions of aspects 1 to 7, wherein the compositions are formulated for oral administration.

[0110] The ninth aspect relates to compositions of aspects 1 to 8, wherein the composition is in the form of tablets, ready-to-drink beverages, concentrates, powders, granules, gels, solids, semi-solids, frozen liquids, lozenges or hard candies, dissolving strips and chewing gum.

[0111] The tenth aspect relates to the compositions of aspects 1 to 9, wherein the composition is a nutritional supplement.

[0112] The eleventh aspect relates to the use of the compositions of aspects 1 to 10 in improving bone health in subjects.

[0113] The twelfth aspect relates to methods for maintaining and / or improving bone health in aging subjects, comprising administering to the subject an effective amount containing N 1 -Dihydrocaffeoyl-N 10 -A composition of caffeoyl spermidine and additives.

[0114] The thirteenth aspect relates to the method of aspect 12, wherein, relative to aging subjects who have not been given the composition, the composition maintains and / or improves bone health in aging subjects by: increasing bone volume fraction (BVF), increasing trabecular thickness (Tb.Th), reducing trabecular separation (Tb.Sp), increasing trabecular number (Tb.N), increasing bone mineral density (BMD), increasing bone mineral content (BMC); and / or increasing bone surface area density (BS / TV) expression.

[0115] The fourteenth aspect relates to the method of aspect 12 or aspect 13, wherein the composition increases spermidine content in a subject within 1 hour after administration of the composition.

[0116] The fifteenth aspect relates to the methods of aspects 12 to 14, wherein the composition comprises at least 10% by weight of N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0117] The sixteenth aspect relates to the methods of aspects 12 to 14, wherein the composition comprises at least 25% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0118] The seventeenth aspect relates to the methods of aspects 12 to 14, wherein the composition comprises at least 45% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0119] The eighteenth aspect relates to the methods of aspects 12 to 17, wherein the composition is administered orally.

[0120] The nineteenth aspect relates to methods for preventing and / or treating bone diseases in subjects, comprising administering to the subjects an effective amount containing N 1 -Dihydrocaffeoyl-N 10 -A composition of caffeoyl spermidine and additives.

[0121] The twentieth aspect relates to the method of aspect 19, wherein the bone disease is osteoporosis, Paget's disease, osteogenesis imperfecta, rickets, osteomalacia, renal osteodystrophy, and / or hyperparathyroidism.

[0122] The twenty-first aspect relates to the method of aspect 19 or 20, wherein the composition comprises at least 10% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0123] The twenty-second aspect relates to the method of aspect 19 or 20, wherein the composition comprises at least 25% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0124] The twenty-third aspect relates to the method of aspect 19 or 20, wherein the composition comprises at least 45% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

[0125] The twenty-fourth aspect relates to the methods of aspects 19 to 23, wherein the composition is administered orally.

[0126] The twenty-fifth aspect relates to the methods of aspects 19 to 24, wherein the composition is a nutritional supplement.

[0127] The twenty-sixth aspect relates to the methods of aspects 19 to 25, wherein the subject is an aging subject.

[0128] In addition to the features mentioned in each of the independent aspects listed above, some examples may be shown individually or in combination of optional features mentioned in the dependent aspects and / or disclosed in the description above and shown in the figures.

Claims

1. A composition for maintaining and / or improving bone health in subjects, comprising N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine and additives.

2. The composition of claim 1, wherein, relative to subjects who have not received the composition, the composition maintains and / or improves bone health in subjects who have received the composition by: Increase bone volume fraction (BVF), Increase trabecular bone thickness (Tb.Th), Reduce trabecular separation (Tb.Sp), Increase the number of trabecular bone (Tb.N), Increase bone mineral density (BMD), Increase bone mineral content (BMC); and / or Increase bone surface area density (BS / TV) expression.

3. The composition of claim 1, wherein the subject is an aging subject.

4. The composition of claim 1, wherein the composition increases spermidine content in the subject within 1 hour after administration of the composition.

5. The composition of claim 1, comprising at least 10% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

6. The composition of claim 1, comprising at least 25% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

7. The composition of claim 1, comprising at least 45% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

8. The composition of claim 1, wherein the composition is formulated for oral administration, wherein N 1 -Dihydrocaffeoyl-N 10 - The dosage of caffeoyl spermidine ranges from 1.5 mg / kg to 50 mg / kg of the subject's body weight.

9. The composition of claim 1, wherein the composition is in the form of tablets, ready-to-drink beverages, concentrates, powders, granules, gels, solids, semi-solids, frozen liquids, lozenges or hard candies, dissolving strips and chewing gum.

10. The composition of claim 1, wherein the composition is a nutritional supplement.

11. Use of the composition of claim 1 for maintaining and / or improving bone health in a subject.

12. A method for maintaining and / or improving bone health in aging subjects, comprising administering an effective amount of a composition to the subject, the composition comprising N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine and additives.

13. The method of claim 12, wherein, relative to aging subjects who have not been given the composition, the composition maintains and / or improves bone health in aging subjects by: Increase bone volume fraction (BVF), Increase trabecular bone thickness (Tb.Th), Reduce trabecular separation (Tb.Sp), Increase the number of trabecular bone (Tb.N), Increase bone mineral density (BMD), Increase bone mineral content (BMC); and / or Increase bone surface area density (BS / TV) expression.

14. The method of claim 12, wherein the composition increases spermidine content in the subject within 1 hour after administration of the composition.

15. The method of claim 12, wherein the composition comprises at least 10% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

16. The method of claim 12, wherein the composition comprises at least 25% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

17. The method of claim 12, wherein the composition comprises at least 45% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

18. The method of claim 12, wherein the composition is administered orally, wherein N 1 -Dihydrocaffeoyl-N 10 The dosage of caffeoyl spermidine ranges from 1.5 mg to 50 mg per kilogram of subject body weight.

19. A method for preventing and / or treating bone diseases in a subject, comprising administering an effective amount of a composition to the subject, the composition comprising N 1 -Dihydrocaffeoyl-N 10 - Caffeoyl spermidine and additives.

20. The method of claim 19, wherein the bone disease is osteoporosis, Paget's disease, osteogenesis imperfecta, rickets, osteomalacia, renal osteodystrophy, or hyperparathyroidism.

21. The method of claim 19, wherein the composition comprises at least 10% by weight N 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

22. The method of claim 19, wherein the composition comprises at least 25% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

23. The method of claim 19, wherein the composition comprises at least 45% by weight N. 1 -Dihydrocaffeoyl-N 10 -Caffeoylsemidine.

24. The method of claim 19, wherein the composition is administered orally, wherein N 1 -Dihydrocaffeoyl-N 10 The dosage of caffeoyl spermidine ranges from 1.5 mg to 50 mg per kilogram of subject body weight.

25. The method of claim 19, wherein the composition is a nutritional supplement.

26. The method of claim 19, wherein the subject is an aging subject.

Images