CN114903916B - 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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- XMWRBQBLMFGWIX-UHFFFAOYSA-N C60 fullerene Chemical group C12=C3C(C4=C56)=C7C8=C5C5=C9C%10=C6C6=C4C1=C1C4=C6C6=C%10C%10=C9C9=C%11C5=C8C5=C8C7=C3C3=C7C2=C1C1=C2C4=C6C4=C%10C6=C9C9=C%11C5=C5C8=C3C3=C7C1=C1C2=C4C6=C2C9=C5C3=C12 XMWRBQBLMFGWIX-UHFFFAOYSA-N 0.000 title claims abstract description 64
- 206010039073 rheumatoid arthritis Diseases 0.000 title claims abstract description 46
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- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
-
- 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]
-
- 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
-
- 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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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Rheumatology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
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Abstract
The invention relates to application of a fullerene structure in preparing a pharmaceutical composition for preventing and/or treating rheumatoid arthritis. The fullerene pharmaceutical composition can inhibit the inflammatory degree of mice with rheumatoid arthritis and relieve the damage of articular cartilage and bones caused by the rheumatoid arthritis.
Description
Technical Field
The invention relates to the field of biological medicine, in particular to an oral fullerene structure and a preparation and application thereof in preventing and/or treating rheumatoid arthritis.
Background
Rheumatoid Arthritis (RA) is a chronic autoimmune joint disease affecting about 1% of the world population, and is frequently found in women and the elderly, and rheumatoid arthritis patients are also prone to other complications, such as cardiovascular disease, which also increase the difficulty of treating rheumatoid arthritis. Although rheumatoid arthritis is a disease caused by an abnormal autoimmune reaction, its underlying pathogenic mechanism is not fully understood, and is currently thought to be triggered by complex interactions of genetic and environmental factors. The disease not only involves small joints of hands and feet, but also is often seen in larger joints, and is characterized by synovitis-related synovial hyperplasia, accompanied by neovascularization, infiltration of lymphocytes and macrophages into synovial tissue, and the like, and in addition, can cause damage to articular cartilage and bone.
To date, various drugs have been approved for use in the treatment of rheumatoid arthritis. The treatment of rheumatoid arthritis has initially been with disease modifying antirheumatic drugs (DMARDs), such as nonsteroidal anti-inflammatory drugs and glucocorticoids. The preferred DMARD is methotrexate, which may be used in combination with other drugs of this type. However, the current therapeutic effects are 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 novel anti-rheumatoid arthritis drugs with good therapeutic effects and less side effects.
Fullerene spherical molecules resemble a sphere, and common fullerenes include C60, C70, C84, and the like. Fullerenes have a highly unsaturated structure and excellent electron acceptor properties, and therefore, fullerenes and functionalized derivatives thereof have been widely used as radical scavengers. Fullerene and derivatives thereof have good antioxidant activity, and can exert a plurality of excellent biological effects, including liver protection, reduction of neuronal damage, life prolongation, regulation of immune cells and the like. At present, many researches show that fullerene and derivatives thereof remarkably inhibit the production of proinflammatory cytokines in vitro, and researches prove that the fullerene and derivatives thereof have therapeutic effects on a plurality of inflammatory disease models, and the results show that the fullerene and derivatives thereof have great application potential in treating autoimmune diseases such as rheumatoid arthritis and the like.
Disclosure of Invention
It is an object of the present invention to provide a use in the preparation of a pharmaceutical composition for the prevention and/or treatment of rheumatoid arthritis. The second object of the present invention is to provide a pharmaceutical composition and a method for preventing and/or treating rheumatoid arthritis using the above-mentioned fullerene pharmaceutical composition. In particular, the pharmaceutical composition of the invention is a preparation which is not suitable for topical administration, in particular, the invention relates to a pharmaceutical composition for oral administration for preventing and/or treating rheumatoid arthritis, wherein 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 for preventing and/or treating rheumatoid arthritis.
Preferably, the pharmaceutical composition is an oral formulation.
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 metallofullerene.
In one embodiment, the functional modification of the fullerene is selected from one or more fullerenes of the group consisting of:
(1) Fullerene with functional groups on the surface,
(2) Fullerene wrapped by functional biological micromolecules,
(3) Fullerenes supported by a biocompatible carrier material,
(4) Self-assembling to form the functional supermolecular system fullerene.
In one embodiment, the fullerene with a surface modified with a functional group includes amino, hydroxyl, carboxyl modified fullerenes.
In one embodiment, the hollow fullerenes are one or more fullerenes of the general formula C 2m Is a cage structure composed of carbon atoms, wherein m is more than or equal to 30 and less than or equal to 60, preferably, m is more than or equal to 30 and less than or equal to 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 One or more of the following, wherein: m, A each represents a metal element and M, A each is selected fromAny one of Sc, Y and lanthanide metal elements, n is more than or equal to 30 and less than or equal to 60,0, and x is more 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, an oral capsule, an oral granule, an oral pill, and/or an oral suspension.
In one embodiment, the oral liquid formulation has a fullerene content of 4mg/mL in the pharmaceutical composition.
In one embodiment, the fullerene structure has an average particle size of 1 to 1000nm, optionally, e.g., 1 to 200nm.
In one embodiment, the method comprises the step of orally administering an effective dose of any of the foregoing pharmaceutical compositions to an organism in need of prevention and/or treatment of rheumatoid arthritis.
In one embodiment, the pharmaceutical composition comprises a form of suspension, and the concentration of use in the organism ranges from 500ppm to 5000ppm.
The beneficial effects are that:
(1) The inventor finds through a large number of experiments that the fullerene structure not only has strong capability of scavenging free radicals, but also can be metabolized in vivo quickly, has good biocompatibility and small toxic and side effects on organisms.
(2) The medicine can be taken orally, is convenient and can be taken for a long time, and is filtered and absorbed by the digestive system, so that the damage to the organism is reduced, the side effect is small, and the curative effect is remarkable.
(3) The medicine can be metabolized out of organisms, has excellent effect of preventing and treating rheumatoid arthritis in vivo due to the effect of efficiently removing free radicals, and can obviously improve joint inflammation, cartilage and bone injury caused by the rheumatoid arthritis.
(4) In the invention, for preventing and treating the rheumatoid arthritis, the fullerene structure can be used as a preventing effect before the rheumatoid arthritis model is mature; at the same time, the composition can remove excessive free radicals in the body after the onset of rheumatoid arthritis, thereby preventing and repairing the damaged joint function and other organ damage in the rheumatoid arthritis
Drawings
FIG. 1 is C 60 Suspension and C 60 -photographs of hind limbs of mice treated with Ala;
FIG. 2 is C 60 A plot of change in joint scores of mice treated with suspension;
FIG. 3 is C 60 A change chart of the average value of the cross-sectional areas of four paws of a mouse with rheumatoid arthritis treated by the suspension;
FIG. 4 is C 60 Hematoxylin-eosin staining of hind limb knee joint sections of mice with rheumatoid arthritis treatment with suspension;
FIG. 5 is C 60 Safranin solid green staining pattern of hind limb knee joint sections of mice with rheumatoid arthritis treatment with suspension;
FIG. 6 is C 60 Tartrate-resistant acid phosphatase staining patterns of hind limb knee joint sections of mice treated with suspension.
Detailed Description
In light of the foregoing disclosure, many other modifications, substitutions, or alterations are also possible in the form of modifications, substitutions, or alterations without departing from the spirit and scope of this disclosure.
I. Definition of the definition
Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations thereof such as "comprises" or "comprising" or the like will be understood to include the stated element or component without excluding other elements or components.
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 being six-membered rings, and is a cage-like structure consisting of carbon atoms. Fullerenes include hollow fullerenes, metallofullerenes, which are cage structures composed solely of carbon atoms.
The term "metallofullerene" refers to a class of compounds having a specific structure and properties, commonly known as endofullerenes, generally M@C, formed by incorporating a variety of atoms, ions, or clusters of atoms into the carbon cage structure of the fullerene 2n The form is represented, wherein M represents a metal element.
The term "water-soluble fullerene" or "fullerene water-soluble modification" refers to a modification of fullerene particles such as hollow fullerene and metal fullerene particles by water-dissolution. The modified fullerene particles are externally modified with a plurality of water-soluble functional groups. The chemical functional groups contain one or more hydrophilic groups such as hydroxyl, carboxyl, sulfhydryl or amino or a combination thereof, so that the fullerene particles can be dissolved in water, or the metal fullerene or the derivative thereof can be directly modified by hydrophilic biological small molecules such as amino acid, peptide chain and the like, or the fullerene or the derivative thereof can be loaded by a carrier material with biocompatibility, such as liposome, cell membrane carrier and the like for coating, or a water-soluble supermolecular system and the like can be formed by self-assembly. The modification methods described above can all be modified according to the methods disclosed in the prior art.
The disclosure of all ranges in this disclosure should be considered to be a disclosure of all subranges and all point values within the range. For example: the disclosure of 1-1000 should be considered as also disclosing ranges from 1-200,200-300, etc., as well as 200, 300, 400, 500, 600, 700, 800, 900, and 100, etc. point values.
The term "treating" includes inhibiting, alleviating, preventing or eliminating one or more symptoms or side effects associated with the disease, condition or disorder being treated.
The terms "reduce", "inhibit", "reduce" or "reduce" are used relative to a control. One skilled in the art will readily determine the appropriate controls for each experiment. For example, a reduced response in a subject or cell treated with a compound is compared to a response in a subject or cell not treated with the compound.
As used herein, the term "effective amount" or "therapeutically effective amount" refers to a dosage sufficient to treat, inhibit or alleviate one or more symptoms of the disease state being treated or otherwise provide the desired pharmacological and/or physiological effect. The precise dosage will vary depending on a variety of factors, such as subject-dependent variables (e.g., age, immune system health, etc.), 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 combination of drugs, or in the case of a combination of drugs, the combined effect 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, disintegrants, wetting agents, emulsifiers, suspending agents, sweeteners, flavoring agents, antibacterial agents, antifungal agents, lubricants, dispersing agents, temperature sensitive materials, temperature adjusting agents, adhesives, stabilizers, suspending agents, and the like.
The foregoing of the present disclosure will be described in further detail by way of the following detailed description of the embodiments. It should not be construed that the scope of the above subject matter of the present disclosure is limited to the following examples. All techniques implemented based on the foregoing disclosure are within the scope of the disclosure.
Examples II
The present disclosure is further illustrated below with reference to examples. The description of specific exemplary embodiments of the present disclosure is presented for purposes of illustration and description. The description 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 the present specification. The exemplary embodiments were chosen and described in order to explain the specific principles of the present disclosure and its practical application to thereby enable one skilled in the art to make and utilize the present disclosure in various exemplary embodiments and with various modifications as are suited to the particular use contemplated.
The experimental methods used in the following examples are conventional methods unless otherwise specified.
Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Example 1: preparation of prototype Fullerene suspension (C) 60 Suspension agent
Fullerene C 60 Mixing solid powder (purchased from Xiamen Funus 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 concentration of 4mg/ml (5.6 mM) of C 60 The suspension was used in the subsequent examples.
Example 2: preparation of amino acid modified fullerenes (C 60 -Ala)
100mg C 60 The solid powder (purchased from Xiamen Funus New materials technology Co., ltd.) was added to 80ml of toluene solution, and the mixture was sonicated 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 ultrasonically adding into the single-neck flask, heating to 80 ℃ in an oil bath, and reacting for 24 hours;
after the reaction, small molecules are removed by using an M.W=3500 dialysis bag, monitoring is performed by using a conductivity meter until the dialysis is completed, and the obtained product is concentrated to obtain the water-soluble amino-acidified fullerene (C60-Ala), wherein the average particle size of the water-soluble amino-acidified fullerene (C60-Ala) in an aqueous solution is 90-100nm through DLS (digital living standard) determination, and the particle size distribution is uniform.
Example 3: c (C) 60 Suspension, C 60 Ala inhibition of limb swelling effect in rheumatoid arthritis mice
Animal model: selecting 7-8 week old DBA/1 male mice, randomly dividing into 3 groups corresponding to normal group, model group, and C 60 Ala treatment group and C 60 Suspension treatment group.
Collagen adjuvant emulsion preparation: under the aseptic condition, a 1ml syringe is used for sucking bovine type II collagen with the concentration of 2mg/ml, another 1ml syringe is used for sucking the same amount of adjuvant, and two syringes are used for pushing and pulling back and forth to ensure that the bovine type II collagen and the adjuvant are fully and evenly mixed until the liquid is milky.
Normal group: the tail root of day 1 was injected with 200 microliters of saline, and 200 microliters of saline was infused daily from day 28 until the end of the experiment on day 48.
Model group: the tail root of day 1 was injected with 200 microliters of bovine type II collagen adjuvant emulsion and 200 microliters of physiological saline was infused daily from day 28 until the end of the experiment at day 48.
C 60 -Ala treatment group: 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the tail on day 1, 200 microliters of 4mg/ml C was intraperitoneally injected every day from day 28 60 Ala to day 48 end of the experiment.
C 60 Suspension treatment group: 200 microliters of bovine type II collagen adjuvant emulsion was injected into the root of the 1 st day tail, 200 microliters of 4mg/ml (5.6 mM) C was infused daily from day 28 60 Suspension until the end of the experiment on day 48.
Mice were first cultured for 1 week to adapt to laboratory conditions, and after the mice had stabilized, they were grouped according to their body weight, as day 1 of the experiment, mice were rheumatoid arthritis modelling and treatment, and other groups remained identical as described in experimental grouping. On the day of sampling, i.e. on day 48 of the experiment, the joint swelling of the limbs of the mice was observed and the hind limbs of the mice of the different groups were photographed for comparison.
The corresponding detection results are shown in FIG. 1, and it can be seen that the hind limb swelling state of the model group mice is obvious, C 60 Ala-treated group did not significantly reduce the swelling of the hind limbs in rheumatoid arthritis mice, whereas C 60 The suspension treatment group was able to significantly reduce the extent of swelling in rheumatoid arthritis mice, bringing them close to normal mouse levels.
Example 4: c (C) 60 Effect of suspension on inhibiting incidence of rheumatoid arthritis in mice
Animal model: selecting 7-8 week old DBA/1 male mice, randomly dividing into 3 groupsRespectively correspond to the normal group, the model group and C 60 Suspension treatment group.
Collagen adjuvant emulsion preparation: under the aseptic condition, a 1ml syringe is used for sucking bovine type II collagen with the concentration of 2mg/ml, another 1ml syringe is used for sucking the same amount of adjuvant, and two syringes are used for pushing and pulling back and forth to ensure that the bovine type II collagen and the adjuvant are fully and evenly mixed until the liquid is milky.
Normal group: the tail root of day 1 was injected with 200 microliters of saline, and 200 microliters of saline was infused daily from day 28 until the end of the experiment on day 48.
Model group: the tail root of day 1 was injected with 200 microliters of bovine type II collagen adjuvant emulsion and 200 microliters of physiological saline was infused daily from day 28 until the end of the experiment at day 48.
C 60 Suspension treatment group: the tail root of day 1 was injected with 200 microliters of bovine type II collagen adjuvant emulsion, 200 microliters of 4mg/ml C60 suspension per day from day 28 and the experiment ended.
Mice were first cultured for 1 week to adapt to laboratory conditions, and after the mice had stabilized, they were grouped according to their body weight, as day 1 of the experiment, mice were rheumatoid arthritis modelling and treatment, and other groups remained identical as described in experimental grouping. The mice were joint scored every 2-3 days after dosing, 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 with vernier calipers until the end of the experiment.
The corresponding detection results are shown in fig. 2 and 3, and it can be seen from fig. 2 that with respect to the model group, C 60 Suspension treatment groups were able to reduce joint scores in rheumatoid arthritis mice, as can be seen from figure 3, C 60 The suspension treatment group can obviously relieve the swelling condition of the paw of the mice with rheumatoid arthritis, which proves that C 60 Suspension treatment can reduce joint swelling of mice and inhibit the incidence of rheumatoid arthritis.
Example 5: c (C) 60 Suspension for inhibiting inflammatory effects of joint in mice with rheumatoid arthritis
Animal model: selecting 7-8 week old DBA/1 male mice, and randomizingIs divided into 3 groups corresponding to the normal group, the model group and C 60 Suspension treatment group.
Collagen adjuvant emulsion preparation: under the aseptic condition, a 1ml syringe is used for sucking bovine type II collagen with the concentration of 2mg/ml, another 1ml syringe is used for sucking the same amount of adjuvant, and two syringes are used for pushing and pulling back and forth to ensure that the bovine type II collagen and the adjuvant are fully and evenly mixed until the liquid is milky.
Normal group: the tail root of day 1 was injected with 200 microliters of saline, and 200 microliters of saline was infused daily from day 28 until the end of the experiment on day 48.
Model group: the tail root of day 1 was injected with 200 microliters of bovine type II collagen adjuvant emulsion and 200 microliters of physiological saline was infused daily from day 28 until the end of the experiment at day 48.
C 60 Suspension treatment group: the tail root of day 1 was injected with 200 microliters of bovine type II collagen adjuvant emulsion, 200 microliters of 4mg/ml C60 suspension per day from day 28 and the experiment ended.
Mice were first cultured for 1 week to adapt to laboratory conditions, and after the mice had stabilized, they were grouped according to their body weight, as day 1 of the experiment, mice were rheumatoid arthritis modelling and treatment, and other groups remained identical as described in experimental grouping. After drawing the material, the hind limb knee joint of the mouse is cut into slices through paraffin embedding and hematoxylin-eosin (HE) staining is carried out to observe the inflammation condition at the joint.
The corresponding detection results are shown in FIG. 4, from which it can be seen that inflammatory cells are accumulated in large amounts at joints of mice in the model group, the inflammatory infiltration is severe, and C 60 The suspension treatment group can obviously relieve inflammatory cell infiltration of the mice with rheumatoid arthritis and inhibit inflammatory infiltration degree.
Example 6: c (C) 60 Effect of suspension in relieving joint cartilage and bone injury in mice with rheumatoid arthritis
Animal model: DBA/1 male mice 7-8 weeks old were selected and randomly divided into 3 groups corresponding to the normal, model and C60 suspension treatment groups, respectively.
Collagen adjuvant emulsion preparation: under the aseptic condition, a 1ml syringe is used for sucking bovine type II collagen with the concentration of 2mg/ml, another 1ml syringe is used for sucking the same amount of adjuvant, and two syringes are used for pushing and pulling back and forth to ensure that the bovine type II collagen and the adjuvant are fully and evenly mixed until the liquid is milky.
Normal group: the tail root of day 1 was injected with 200 microliters of saline, and 200 microliters of saline was infused daily from day 28 until the end of the experiment on day 48.
Model group: the tail root of day 1 was injected with 200 microliters of bovine type II collagen adjuvant emulsion and 200 microliters of physiological saline was infused daily from day 28 until the end of the experiment at day 48.
C 60 Suspension treatment group: the tail root of day 1 was injected with 200 microliters of bovine type II collagen adjuvant emulsion, 200 microliters of 4mg/ml C60 suspension per day from day 28 and the experiment ended.
Mice were first cultured for 1 week to adapt to laboratory conditions, and after the mice had stabilized, they were grouped according to their body weight, as day 1 of the experiment, mice were rheumatoid arthritis modelling and treatment, and other groups remained identical as described in experimental grouping. After the materials are taken, the knee joints of the hind limbs of the mice are cut by paraffin embedding and are subjected to safranine and fast green staining, wherein basophilic cartilage tissues are combined with basic dye safranine to be red, and acidophilic bone tissues are combined with acid dye fast green to be green or blue, so that the damage condition of the articular cartilage and bones of the mice can be observed. In addition, the number of osteoclasts at the joint was observed by performing a tartrate-resistant acid phosphatase (Trap) staining, which reddish-colored the osteoclasts to show the distribution and number of osteoclasts.
The corresponding detection results are shown in fig. 5 and 6, and it can be seen from fig. 5 that the articular cartilage and bone of the mice in the model group are damaged in large area, and the bone is corroded seriously, C 60 The suspension treatment group can significantly reduce the damage and absence of articular cartilage and bones of the mice with rheumatoid arthritis. As can be seen from FIG. 6, the model group mice contained a large number of osteoclasts in their joints, whereas C 60 The suspension treatment group can remarkably reduce the number of osteoclast at joint of mice with rheumatoid arthritis, inhibit the generation and aggregation of osteoclast, thereby reducing the number of the cellsDestruction of cartilage and bone.
The foregoing descriptions of specific exemplary embodiments of the present invention are 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 the specific principles of the invention and its practical application to thereby enable one skilled in the art to make and utilize the invention in various exemplary embodiments and with various 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 (3)
1. The application of the fullerene structure in preparing a pharmaceutical composition for treating rheumatoid arthritis is characterized in that the pharmaceutical composition is an oral suspension,
the fullerene structure is water insoluble fullerene,
the fullerene is C 60 ,
The oral suspension is prepared from fullerene C 60 Uniformly mixing the solid powder and auxiliary materials containing microcrystalline cellulose, copovidone and glyceryl behenate, and pressing into tablets by a tablet press; dissolving tablet with ultrapure water to give C with concentration of 4mg/ml 60 A suspension.
2. The use according to claim 1, wherein the fullerene structure has an average particle size of 1 to 1000nm.
3. The use according to claim 2, wherein the fullerene structure has an average particle size of 1 to 200nm.
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