CN114903916A - Oral fullerene structure and preparation and application thereof in preventing and treating rheumatoid arthritis - Google Patents
Oral fullerene structure and preparation and application thereof in preventing and treating rheumatoid arthritis Download PDFInfo
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- CN114903916A CN114903916A CN202210463058.4A CN202210463058A CN114903916A CN 114903916 A CN114903916 A CN 114903916A CN 202210463058 A CN202210463058 A CN 202210463058A CN 114903916 A CN114903916 A CN 114903916A
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- fullerene
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- rheumatoid arthritis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/44—Elemental carbon, e.g. charcoal, carbon black
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/16—Inorganic salts, minerals or trace elements
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/244—Lanthanides; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention relates to application of a fullerene structure in preparation of a pharmaceutical composition or a health-care food composition for preventing and/or treating rheumatoid arthritis. The fullerene pharmaceutical composition or the health-care food composition can inhibit the inflammation degree of a mouse with rheumatoid arthritis and relieve the destruction of articular cartilage and bones caused by the rheumatoid arthritis.
Description
Technical Field
The invention relates to the field of biomedicine, in particular to an oral fullerene structure, a preparation and application of the oral fullerene structure and the preparation in preventing and/or treating rheumatoid arthritis.
Background
Rheumatoid Arthritis (RA) is a chronic autoimmune joint disease that affects approximately 1% of the world population, is prevalent in women and the elderly, and is also prone to other complications, such as cardiovascular disease, that increase the difficulty of treating rheumatoid arthritis. Although rheumatoid arthritis is a disease caused by abnormal autoimmune reactions, its underlying pathogenic mechanism is not fully understood, and is currently thought to be triggered by a complex interaction of genetic and environmental factors. The disease involves not only the small joints of the hands and feet but also the larger joints, which are characterized by synovitis-associated synovial hyperplasia with angiogenesis, infiltration of lymphocytes and macrophages into synovial tissue, etc., and in addition, damage to articular cartilage and bone.
To date, a variety of drugs have been licensed for use as a treatment for rheumatoid arthritis. The treatment of rheumatoid arthritis initially used disease modifying antirheumatic drugs (DMARDs) such as non-steroidal anti-inflammatory drugs and glucocorticoids. The preferred DMARD is methotrexate, which can be used in combination with other drugs of this type. However, the current therapeutic effect is still unsatisfactory, and when arthritis is severe, such drugs do not provide a good therapeutic effect, and DMARDs also exert toxic effects. Therefore, there is still an urgent need to find a novel anti-rheumatoid arthritis drug with good therapeutic effect and less side effects.
Fullerene spherical molecules resemble a sphere, and common fullerenes are C60, C70, C84, and the like. Fullerenes have a highly unsaturated structure and excellent electron acceptor properties, and thus fullerenes and functionalized derivatives thereof have been widely used as radical scavengers. The fullerene and the fullerene derivative have good antioxidant activity, and can play a plurality of excellent biological effects, including liver protection, neuron damage reduction, life prolongation, immune cell regulation and the like. At present, many studies show that the fullerene and the derivatives thereof remarkably inhibit the production of proinflammatory cytokines in vitro, and the research proves that the fullerene and the derivatives thereof have the treatment effect on many inflammatory disease models, and the results show that the fullerene and the derivatives thereof have great application potential in treating autoimmune diseases such as rheumatoid arthritis and the like.
Disclosure of Invention
The invention aims to provide application of a medicine composition or a health-care food composition for preventing and/or treating rheumatoid arthritis. The invention also aims to provide a pharmaceutical composition and a method for preventing and/or treating rheumatoid arthritis by using the fullerene pharmaceutical composition or the health-care food composition. The invention also aims to provide a health-care food composition or a health-care product which uses fullerene and can improve rheumatoid arthritis. In particular, the pharmaceutical composition or health food composition of the present invention is a preparation not suitable for topical administration, and in particular, the present invention relates to a pharmaceutical composition or health food composition for prevention and/or treatment of rheumatoid arthritis for oral administration, in which the fullerene structure used is water-insoluble.
In order to solve the technical problems, the invention provides application of a fullerene structure in preparing a pharmaceutical composition or a health-care food composition for preventing and/or treating rheumatoid arthritis.
Preferably, the pharmaceutical composition or the health food composition is an oral preparation.
In one embodiment, the fullerene structure is a water insoluble fullerene.
In one embodiment, the fullerene structure comprises one or more of a prototype fullerene, a functionalized modification of a fullerene.
In one embodiment, the prototype fullerene comprises one or more of a hollow fullerene, a metallic fullerene.
In one embodiment, the functionalized modification of a fullerene is selected from one or more fullerenes of the group:
(1) the surface of the fullerene is modified with functional groups,
(2) fullerene wrapped by functional biological small molecules,
(3) fullerenes loaded with a biocompatible carrier material,
(4) self-assembled to form the functional supermolecular system fullerene.
In one embodiment, the fullerene with the surface modified with the functional group comprises an amino group, a hydroxyl group and a carboxyl group modified fullerene.
In one embodiment, the hollow fullerene is one or more compounds of the formula C 2m 30 < m > 60, preferably 30 < m > 45; more preferably, m is 30, 35 or 42.
In one embodiment, the metallofullerene comprises M @ C 2n 、M 2 @C 2n 、MA@C 2n 、M 3 N@C 2n 、M 2 C 2 @C 2n 、M 2 S@C 2n 、M 2 O@C 2n And M x A 3-x N@C 2n Wherein: m, A all represent metal elements, M, A are all selected from any one of Sc, Y and lanthanide metal elements, n is more than or equal to 30 and less than or equal to 60, and x is more than or equal to 0 and less than or equal to 3; preferably, the metallofullerene is Gd @ C 82 。
In one embodiment, the fullerene is a prototype fullerene.
In one embodiment, the fullerene is C 60 。
In one embodiment, the oral formulation comprises an oral solid formulation or an oral liquid formulation.
In one embodiment, the pharmaceutical composition is an oral tablet, oral capsule, oral granule, oral pill, and/or oral suspension.
In one embodiment, the pharmaceutical composition of the oral liquid formulation has a fullerene content of 4 mg/mL.
In one embodiment, the fullerene structure has an average particle size of 1 to 1000nm, optionally such as an average particle size of 1 to 200 nm.
In one embodiment, the method comprises the step of orally administering an effective dose of any one of the aforementioned pharmaceutical compositions or nutraceutical compositions in vivo to an organism in need of prevention and/or treatment of rheumatoid arthritis.
In one embodiment, the pharmaceutical composition or health food composition comprises a form of suspension, and is used in a concentration range of 500ppm to 5000ppm in an organism.
Has the advantages that:
(1) the inventor finds out through a large number of experiments that the fullerene structure not only has stronger capability of removing free radicals, but also can be metabolized in vivo faster, has good biocompatibility and has small toxic and side effects on organisms.
(2) The medicine can be orally taken, is convenient for long-term administration, can be filtered and absorbed by a digestive system, reduces the body injury, and has small side effect and remarkable curative effect.
(3) The medicine can be metabolized out of organisms, has excellent effect of preventing and treating rheumatoid arthritis in vivo due to its high effect of scavenging free radicals, and can obviously improve joint red swelling, joint inflammation, cartilage and bone injury caused by rheumatoid arthritis.
(4) For the prevention and treatment of rheumatoid arthritis, the fullerene structure can be used as a prevention effect before a rheumatoid arthritis model is mature; simultaneously, can remove excessive free radicals in vivo after the onset of rheumatoid arthritis, thereby preventing and repairing the damaged joint function and other organ injuries in the rheumatoid arthritis
Drawings
FIG. 1 is C 60 Suspensions and C 60 -photographs of the hind limbs of Ala-treated rheumatoid arthritis mice;
FIG. 2 is C 60 Change graph of joint score of mice treated with the suspension for rheumatoid arthritis;
FIG. 3 is C 60 Graph of the mean change of the cross-sectional area of the four paws of the mouse treated by the suspension;
FIG. 4 is C 60 Hematoxylin-eosin staining pattern of the suspension for treating rheumatoid arthritis mouse hind limb knee joint section;
FIG. 5 is C 60 The safranin fast green staining pattern of the joint section of the hind limb and the knee of the mouse for treating rheumatoid arthritis by using the suspension;
FIG. 6 is C 60 Suspension for treating rheumatoid arthritis mouse hind limb kneeStaining pattern of anti-tartrate acid phosphatase of joint sections.
Detailed Description
Based on the above disclosure, other modifications, substitutions and alterations can be made without departing from the basic technical concept of the present disclosure as it is known and customary in the art.
I. Definition of
Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations such as "comprises" or "comprising", etc., will be understood to imply the inclusion of a stated element or component but not the exclusion of any other element or component.
As used herein, the term "fullerene" is a series of spheroidal cluster molecules consisting of an even number of carbon atoms, with 12 five-membered rings and the remainder six-membered rings, and is a cage-like structure consisting of carbon atoms. Fullerenes include hollow fullerenes, which are cage-like structures composed solely of carbon atoms, metallic fullerenes.
The term "metallofullerene" refers to a class of compounds having specific structures and properties formed by the inclusion of various atoms, ions or clusters of atoms within the carbon cage structure of a fullerene, commonly referred to as endohedral fullerenes, commonly referred to as M @ C 2n Formal representation, wherein M represents a metal element.
The term "water-soluble fullerene" or "fullerene water-soluble modifier" refers to water-soluble modification of fullerene particles such as hollow fullerene particles and metal fullerene particles. The exterior of the modified fullerene particle is modified with a plurality of water-soluble functional groups. These chemical functional groups contain one or more hydrophilic groups such as hydroxyl, carboxyl, sulfhydryl or amino groups or their combination, which makes the fullerene particles soluble in water, or directly modifies the metal fullerene or its derivatives with hydrophilic biological small molecules such as amino acids, peptide chains, etc., or carries the fullerene or its derivatives with the help of biocompatible carrier materials, such as liposomes, cell membrane carriers, etc., or forms water-soluble supermolecular systems by self-assembly, etc. The above modification methods can be modified according to the methods disclosed in the prior art.
The disclosure of all ranges herein should be considered as disclosing all sub-ranges and all point values within the range. For example: the disclosure of 1-1000 should be considered to disclose the range of 1-200,200-300, etc., as well as 200, 300, 400, 500, 600, 700, 800, 900, and 100, etc.
The term "treating" includes inhibiting, alleviating, preventing or eliminating one or more symptoms or side effects associated with the disease, disorder or condition being treated.
The terms "reduce", "inhibit", "reduce" or "decrease" are used relative to a control. One skilled in the art will readily determine the appropriate control for each experiment. For example, a decreased response in a subject or cell treated with a compound is compared to a response in a subject or cell not treated with a compound.
As used herein, the term "effective amount" or "therapeutically effective amount" refers to a dose sufficient to treat, inhibit or alleviate one or more symptoms of the disease state being treated or to otherwise provide a desired pharmacological and/or physiological effect. The precise dosage will vary depending on a variety of factors, such as the subject-dependent variables (e.g., age, immune system health, etc.), the disease or disorder, and the treatment being administered. The effect of an effective amount may be relative to a control. These controls are known in the art and discussed herein, and may be, for example, the condition of the subject prior to or without administration of the drug or drug combination, or in the case of a drug combination, the effect of the combination may be compared to the effect of administration of only one drug.
The term "pharmaceutical composition" means a composition comprising a fullerene and, depending on the mode of administration and the nature of the dosage form, at least one pharmaceutically acceptable ingredient selected from the group consisting of, but not limited to: carriers, diluents, adjuvants, excipients, preservatives, fillers, disintegrating agents, wetting agents, emulsifiers, suspending agents, sweeteners, flavoring agents, fragrances, antibacterial agents, antifungal agents, lubricants, dispersants, temperature sensitive materials, temperature regulating agents, adhesives, stabilizers, suspending agents, and the like.
The foregoing and other aspects of the present disclosure are apparent from the following more particular description of the embodiments, as illustrated in the accompanying drawings. It should not be understood that the scope of the above-described subject matter of the present disclosure is limited to the following examples. All the technologies realized based on the above contents of the present disclosure belong to the scope of the present disclosure.
Example II
The present disclosure is further illustrated below with reference to examples. The description of the specific exemplary embodiments of the present disclosure has been presented for purposes of illustration and description. It is not intended to limit the disclosure to the precise form disclosed, and obviously many modifications and variations are possible in light of the teaching of this specification. The exemplary embodiments were chosen and described in order to explain certain principles of the disclosure and its practical application to enable one skilled in the art to make and use various exemplary embodiments of the disclosure and various alternatives and modifications thereof.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1: preparation of prototype Fullerene suspension (C) 60 Suspension agent
Reacting fullerene C 60 Mixing solid powder (purchased from Xiamen new materials science and technology Co., Ltd.), microcrystalline cellulose, copovidone, glyceryl behenate, etc., and tabletting; prior to animal experiments, the tablets were dissolved in ultrapure water to a C concentration of 4mg/ml (5.6mM) 60 The suspension was used in the subsequent examples.
Example 2: preparation of amino acid-modified Fullerene (C) 60 -Ala)
Mixing 100mg of C 60 The solid powder (purchased from Xiamen New materials science and technology Co., Ltd.) was added to 80ml of a toluene solution, ultrasonically dissolved, and transferred to a 250ml single-neck flask.
Adding 3g of beta-alanine and 6g of sodium hydroxide into 9ml of aqueous solution, adding 18ml of ethanol, uniformly performing ultrasonic treatment, dropwise adding the mixture into an oil bath in the single-neck flask, heating to 80 ℃, and reacting for 24 hours;
after the reaction, small molecules were removed by using a dialysis bag of m.w. ═ 3500, and the mixture was monitored by a conductivity meter until the completion of dialysis, and the obtained product was concentrated to obtain a water-soluble amino-acidified fullerene (C60-Ala), which had an average particle diameter of 90 to 100nm in an aqueous solution and a uniform particle diameter distribution as measured by DLS.
Example 3: c 60 Suspension, C 60 Effect of Ala in suppressing swelling of limbs in Rheumatoid arthritis mouse
Animal model: selecting 7-8 week-old DBA/1 male mice, randomly dividing into 3 groups, respectively corresponding to normal group, model group, and C 60 Ala treatment group and C 60 Suspension treatment group.
Preparation of collagen adjuvant emulsion: under the aseptic condition, 1ml of injector is used for sucking bovine type II collagen with the concentration of 2mg/ml, another 1ml of injector is used for sucking the same amount of adjuvant, and the two injectors are pushed and pulled back and forth to ensure that the bovine type II collagen and the adjuvant are fully and uniformly mixed until the liquid is milky white.
Normal group: on day 1, 200. mu.l of saline was injected into the root of the tail, and 200. mu.l of saline was gavaged daily from day 28 to the end of the experiment on day 48.
Model group: on day 1, 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and 200 microliters of physiological saline was perfused daily from day 28 to the end of the experiment on day 48.
C 60 -Ala treatment group: on day 1, 200. mu.l of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and from day 28, 200. mu.l of 4mg/ml C was intraperitoneally injected daily 60 Ala to the end of the experiment by day 48.
C 60 Suspension treatment group: on day 1, 200. mu.l of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and 200. mu.l of 4mg/ml (5.6mM) C was gavaged daily from day 28 60 Suspension to the end of the experiment by day 48.
The mice are cultured for 1 week, adapted to the laboratory environment, and grouped according to the weight of the mice after the mice are stable as the 1 st day of the experiment, and the mouse rheumatoid arthritis modeling and treatment are consistent in each group of other operations as described in the experimental grouping condition. The swelling of the joints of the four limbs of the mice was observed on the day of material collection, i.e., on the 48 th day of the experiment, and the hind limbs of the mice of different groups were photographed and compared.
The corresponding detection results are shown in FIG. 1, and it can be seen that the swelling state of hind limbs of the mice in the model group is obvious, C 60 the-Ala treatment group did not significantly reduce swelling of the hind limbs in rheumatoid arthritis mice, while C 60 The suspension treatment group can obviously reduce the swelling degree of the rheumatoid arthritis mice to be close to the level of normal mice.
Example 4: c 60 Effect of the suspension on inhibiting the degree of onset of rheumatoid arthritis in mice
Animal model: selecting 7-8 week-old DBA/1 male mice, randomly dividing into 3 groups, respectively corresponding to normal group, model group and C 60 Suspension treatment group.
Preparation of collagen adjuvant emulsion: under the aseptic condition, 1ml of injector is used for sucking bovine type II collagen with the concentration of 2mg/ml, another 1ml of injector is used for sucking the same amount of adjuvant, and the two injectors are pushed and pulled back and forth to ensure that the bovine type II collagen and the adjuvant are fully and uniformly mixed until the liquid is milky white.
Normal group: 200 microliters of normal saline was injected into the root on day 1, and 200 microliters of normal saline was gavaged daily from day 28 to the end of the experiment on day 48.
Model group: on day 1, 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and 200 microliters of physiological saline was perfused daily from day 28 to the end of the experiment on day 48.
C 60 Suspension treatment group: on day 1, 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and 200 microliters of 4mg/ml C60 suspension was perfused daily from day 28 until the end of the experiment on day 48.
The mice are cultured for 1 week, adapted to the laboratory environment, and grouped according to the weight of the mice after the mice are stable as the 1 st day of the experiment, and the mouse rheumatoid arthritis modeling and treatment are consistent in each group of other operations as described in the experimental grouping condition. The mice were scored for joints every 2-3 days after the administration, and the average of the cross-sectional areas of the four paws of the mice was calculated by measuring the width and thickness of the four paws of the mice with a vernier caliper until the end of the experiment.
The corresponding detection results are shown in FIGS. 2 and 3, and it can be seen from FIG. 2 that C is the relative model group 60 The suspension treatment group was able to reduce rheumatoid arthritis mouse joint scores, as can be seen in FIG. 3C 60 The suspension treatment group can obviously relieve the swelling condition of the mouse paw with rheumatoid arthritis, and the result shows that C 60 The suspension treatment can reduce the joint swelling condition of mice and inhibit the incidence degree of rheumatoid arthritis.
Example 5: c 60 Inflammation inhibiting effect of suspension on joint of mouse with rheumatoid arthritis
Animal model: selecting 7-8 week-old DBA/1 male mice, randomly dividing into 3 groups, respectively corresponding to normal group, model group and C 60 Suspension treatment group.
Preparation of collagen adjuvant emulsion: under the aseptic condition, 1ml of injector is used for sucking bovine type II collagen with the concentration of 2mg/ml, another 1ml of injector is used for sucking the same amount of adjuvant, and the two injectors are pushed and pulled back and forth to ensure that the bovine type II collagen and the adjuvant are fully and uniformly mixed until the liquid is milky white.
Normal group: on day 1, 200. mu.l of saline was injected into the root of the tail, and 200. mu.l of saline was gavaged daily from day 28 to the end of the experiment on day 48.
Model group: on day 1, 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and from day 28, 200 microliters of physiological saline was perfused daily until the end of the experiment on day 48.
C 60 Suspension treatment group: on day 1, 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and 200 microliters of 4mg/ml C60 suspension was perfused daily from day 28 until the end of the experiment on day 48.
The mice are cultured for 1 week, adapted to the laboratory environment, and grouped according to the weight of the mice after the mice are stable as the 1 st day of the experiment, and the mouse rheumatoid arthritis modeling and treatment are consistent in each group of other operations as described in the experimental grouping condition. After the materials are taken, the hind limb knee joint of the mouse is sectioned by paraffin embedding and hematoxylin-eosin (HE) staining to observe the inflammation condition of the joint.
The corresponding test results are shown in FIG. 4, which shows that a large amount of inflammatory cells are accumulated at the joints of the mice in the model group, the inflammatory infiltration condition is serious, and C is 60 The suspension treatment group can remarkably relieve the inflammatory cell infiltration condition of the rheumatoid arthritis mice and inhibit the inflammatory infiltration degree.
Example 6: c 60 Effect of suspension on relieving articular cartilage and bone injury of rheumatoid arthritis mice
Animal model: 7-8 weeks old DBA/1 male mice were selected and randomized into 3 groups, corresponding to the normal, model and C60 suspension treatment groups.
Preparation of collagen adjuvant emulsion: under the aseptic condition, 1ml of injector is used for sucking bovine type II collagen with the concentration of 2mg/ml, another 1ml of injector is used for sucking the same amount of adjuvant, and the two injectors are pushed and pulled back and forth to ensure that the bovine type II collagen and the adjuvant are fully and uniformly mixed until the liquid is milky white.
Normal group: on day 1, 200. mu.l of saline was injected into the root of the tail, and 200. mu.l of saline was gavaged daily from day 28 to the end of the experiment on day 48.
Model group: on day 1, 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and 200 microliters of physiological saline was perfused daily from day 28 to the end of the experiment on day 48.
C 60 Suspension treatment group: on day 1, 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the tail, and 200 microliters of 4mg/ml C60 suspension was gavaged daily from day 28 until the end of the experiment on day 48.
The mice are cultured for 1 week, the laboratory environment is adapted, the mice are grouped according to the weights of the mice after the mice are stable, the day 1 of the experiment is taken, the mouse rheumatoid arthritis modeling and treatment are as described in the experimental grouping condition, and other operation groups are kept consistent. After material taking, the mouse hind limb knee joint is sectioned through paraffin embedding and stained with safranin fast green, wherein basophilic cartilage tissue is combined with basic dye safranin to show red, and acidophilic bone tissue is combined with acid dye fast green to show green or blue, so that the damage condition of the mouse joint cartilage and bone can be observed. In addition, the number of osteoclasts in the joint was observed by tartrate-resistant acid phosphatase (Trap) staining, which shows the distribution and number of osteoclasts, in order to make osteoclasts red.
The corresponding test results are shown in fig. 5 and 6, and it can be seen from fig. 5 that the articular cartilage and bone of the mouse in the model group are both destroyed in a large area, the bone is severely eroded, and C 60 The suspension treatment group can obviously reduce the damage and the loss of articular cartilage and bones of the mouse with the rheumatoid arthritis. As can be seen from FIG. 6, the joint of the model group mouse contains a large amount of osteoclasts, while C 60 The suspension treatment group can obviously reduce the number of osteoclast at the joint of the mouse with rheumatoid arthritis, and inhibit the generation and aggregation of osteoclast, thereby reducing the damage to cartilage and bone.
The foregoing descriptions of specific exemplary embodiments of the present invention have been presented for purposes of illustration and description. It is not intended to limit the invention to the precise form disclosed, and obviously many modifications and variations are possible in light of the above teaching. The exemplary embodiments were chosen and described in order to explain certain principles of the invention and its practical application to enable one skilled in the art to make and use various exemplary embodiments of the invention and various alternatives and modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims and their equivalents.
Claims (10)
1. The application of the fullerene structure in preparing a pharmaceutical composition or a health-care food composition for preventing and/or treating rheumatoid arthritis is characterized in that the pharmaceutical composition or the health-care food composition is an oral preparation,
the fullerene structure is a water-insoluble fullerene.
2. Use according to claim 1, wherein the fullerene structure comprises one or more of a prototype fullerene, a functionalized modification of a fullerene,
the prototype fullerene comprises one or more of hollow fullerene and metal fullerene,
the functional modifier of the fullerene is one or more fullerenes selected from the group consisting of:
(1) the surface of the fullerene is modified with functional groups,
(2) fullerene wrapped by functional biological small molecules,
(3) fullerenes loaded with a biocompatible carrier material,
(4) self-assembled to form the functional supermolecular system fullerene.
3. The use according to claim 2, wherein the fullerene having a functionalized group modified on the surface thereof comprises an amino, hydroxyl, or carboxyl group modified fullerene.
4. Use according to claim 1 or 2, wherein the hollow fullerene is one or more of the general formula C 2m 30. ltoreq. m.ltoreq.60, preferably 30. ltoreq. m.ltoreq.45; more preferably, m is 30, 35 or 42;
the metal fullerene comprises M @ C 2n 、M 2 @C 2n 、MA@C 2n 、M 3 N@C 2n 、M 2 C 2 @C 2n 、M 2 S@C 2n 、M 2 O@C 2n And M x A 3-x N@C 2n Wherein: m, A all represent metal elements, M, A all represent any one of Sc, Y and lanthanide series metal elements, n is more than or equal to 30 and less than or equal to 60, and x is more than or equal to 0 and less than or equal to 3; preferably, the metallofullerene is Gd @ C 82 。
5. Use according to any one of claims 1-4, wherein the fullerene is a prototype fullerene, preferably the fullerene is C 60 。
6. The use according to any one of claims 1 to 5, wherein the oral formulation comprises an oral solid formulation or an oral liquid formulation.
7. The use according to claim 6, wherein the pharmaceutical composition is an oral tablet, an oral capsule, an oral granule, an oral pill or an oral suspension.
8. Use according to any one of claims 1-7, wherein the fullerene structure has an average particle size of 1 to 1000nm, optionally such as an average particle size of 1 to 200 nm.
9. A method for preventing and/or treating rheumatoid arthritis, comprising the step of orally administering an effective dose of the pharmaceutical composition or nutraceutical composition of any one of claims 1 to 7 in vivo to a living body of rheumatoid arthritis in need of prevention and/or treatment.
10. The method of claim 9, wherein: the pharmaceutical composition or health food composition comprises a suspension, and the use concentration in the living body ranges from 500ppm to 5000 ppm.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101098684A (en) * | 2004-12-07 | 2008-01-02 | 维生素C60生化学研究公司 | Preventive/therapeutic composition for free radical disease |
| US20100040599A1 (en) * | 2006-10-20 | 2010-02-18 | St. Marianna University School Of Medicine | Therapeutic agent for rheumatoid arthritis |
| US20110028522A1 (en) * | 2008-03-03 | 2011-02-03 | Luna Innovations Incorporated | Fullerene therapies for inflammation |
| US20110251158A1 (en) * | 2008-03-03 | 2011-10-13 | Luna Innovations Incorporated | Fullerene therapies for inflammation and inhibition of build-up of arterial plaque |
| CN109568555A (en) * | 2019-01-15 | 2019-04-05 | 张庆华 | A kind of external application quantum microcirculation energy helps sun patch and preparation method thereof |
| CN113648331A (en) * | 2021-08-30 | 2021-11-16 | 中国科学院化学研究所 | Application of oral fullerene material in preparation of medicine for treating gastric ulcer |
-
2022
- 2022-04-28 CN CN202210463058.4A patent/CN114903916B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101098684A (en) * | 2004-12-07 | 2008-01-02 | 维生素C60生化学研究公司 | Preventive/therapeutic composition for free radical disease |
| US20100040599A1 (en) * | 2006-10-20 | 2010-02-18 | St. Marianna University School Of Medicine | Therapeutic agent for rheumatoid arthritis |
| US20110028522A1 (en) * | 2008-03-03 | 2011-02-03 | Luna Innovations Incorporated | Fullerene therapies for inflammation |
| US20110251158A1 (en) * | 2008-03-03 | 2011-10-13 | Luna Innovations Incorporated | Fullerene therapies for inflammation and inhibition of build-up of arterial plaque |
| CN109568555A (en) * | 2019-01-15 | 2019-04-05 | 张庆华 | A kind of external application quantum microcirculation energy helps sun patch and preparation method thereof |
| CN113648331A (en) * | 2021-08-30 | 2021-11-16 | 中国科学院化学研究所 | Application of oral fullerene material in preparation of medicine for treating gastric ulcer |
Non-Patent Citations (2)
| Title |
|---|
| 张茂清 等: "现代药理学与药物治疗基础", vol. 1, 吉林科学技术出版社, pages: 8 * |
| 张金超等: "碳纳米材料在生物医学领域的应用现状及展望", 《化学进展》, vol. 25, no. 2, 24 March 2013 (2013-03-24), pages 236 - 247 * |
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