CN111035764B - Composition for treating rheumatoid arthritis and preparation method thereof - Google Patents
Composition for treating rheumatoid arthritis and preparation method thereof Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
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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]
Abstract
The invention discloses a pharmaceutical composition for treating rheumatoid arthritis, which is a preparation prepared from the following active ingredients: non-steroidal anti-inflammatory drugs, K (D) PT. The pharmaceutical composition can be prepared into oral preparations, and provides a more effective and safer treatment means for rheumatoid arthritis. The pharmacodynamic experiment proves that the pharmaceutical composition can reduce the dosage of the non-steroidal anti-inflammatory drug and reduce the side effect thereof under the condition of ensuring and even improving the curative effect, and provides a new safe and effective drug selection for patients.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a pharmaceutical composition for treating rheumatoid arthritis and a preparation method thereof.
Background
Rheumatoid Arthritis (RA) is a chronic autoimmune disease mainly characterized by inflammatory synovitis, the exact pathogenesis is unknown, and the disease is characterized by polyarticular, symmetrical and invasive joint inflammation of small joints of hands and feet, often accompanied by the involvement of external organs of joints, and also can cause joint deformity and function loss. The worldwide incidence of RA is 0.5% -1%, the incidence of RA in China is 0.32% -0.36%, 63% of patients can cause disability within 10 years of incidence, the survival quality of the patients is seriously affected, and the disease is a disease with high harm. Currently, examples of drugs for treating RA include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-controlling slow acting drugs (DMARDs), and biologies.
The non-steroidal anti-inflammatory drug is a first-line treatment drug for rheumatoid arthritis, and comprises ibuprofen, aspirin, diclofenac and the like. NSAIDs reduce the metabolism of arachidonic acid to prostaglandins by inhibiting cyclooxygenase, achieve the purpose of controlling joint pain, have the effects of anti-inflammation and pain relief, and are indispensable nonspecific symptomatic treatment drugs for treating RA. However, the irritation of these drugs to the gastrointestinal mucosa greatly limits the clinical application of these drugs, and thus, it is of great importance to the patient to reduce the therapeutic dose of the drugs for treating rheumatoid arthritis and to reduce or alleviate the side effects while maintaining or improving the therapeutic effect.
K (d) PT is a tripeptide, the C-terminal region of α MSH, a newly developed drug for the treatment of chronic bowel disease, which is not cytotoxic.
The inventor of the invention finds that the effect of K (D) PT on treating rheumatoid arthritis is not obvious, joint swelling is not obviously improved when the K (D) PT is used alone, but the K (D) PT has the effect of increasing the antirheumatic effect of non-steroidal anti-inflammatory drugs and improving the side effect of the non-steroidal anti-inflammatory drugs when the K (D) PT is used in combination with the non-steroidal anti-inflammatory drugs. The combined application of the non-steroidal anti-inflammatory drug and K (D) PT has good treatment effect on the rheumatoid arthritis.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for treating rheumatoid arthritis, which solves the problems of poor curative effect and adverse reaction of the existing medicines.
The invention provides a pharmaceutical composition for treating rheumatoid arthritis, which is a preparation prepared from the following raw material medicines: contains non-steroidal anti-inflammatory drug and K (D) PT.
The pharmaceutical composition is characterized in that the weight ratio of the non-steroidal anti-inflammatory drug to the K (D) PT is (0.1-30): 1.
The pharmaceutical composition as described above, in particular embodiments, is characterized by: the weight ratio of the non-steroidal anti-inflammatory drug to the K (D) PT is (0.3-20): 1.
Wherein the non-steroidal anti-inflammatory drug is selected from aspirin, acetaminophen, indomethacin, naproxen, naproxone, diclofenac, ibuprofen, nimesulide, rofecoxib and celecoxib.
The pharmaceutical composition of K (D) PT and the non-steroidal anti-inflammatory drug is an oral preparation.
Alternative dosage forms for oral administration of the pharmaceutical compositions of k (d) PT and non-steroidal anti-inflammatory drugs described in the present invention include, but are not limited to: tablet, granule, capsule, and solution.
The invention relates to a pharmaceutical composition of K (D) PT and a non-steroidal anti-inflammatory drug, and selected auxiliary materials comprise: starch, pregelatinized starch, starch slurry, dextrin, microcrystalline cellulose, vitamin E, hydroxypropyl methyl cellulose, low-substituted hydroxypropyl cellulose, calcium carboxymethyl cellulose, polyethylene glycol (PEG), sodium carboxymethyl cellulose, methyl cellulose, ethyl cellulose, mannitol, lactose, polyvinylpyrrolidone (PVP), cross-linked polyvinylpyrrolidone, magnesium stearate, talc, aerosil, sodium bicarbonate, sodium carbonate, and enteric coating powder.
Compared with the prior art, the pharmaceutical composition provided by the invention can effectively improve joint swelling caused by rheumatoid arthritis, reduce the dosage of the non-steroidal anti-inflammatory drug, reduce side effects, and increase the safety of medication and the compliance of patients.
Detailed Description
The present invention is described in further detail below with reference to specific examples so that those skilled in the art can further understand the present invention. The examples should not be construed as limiting the scope of protection.
EXAMPLE 1 preparation of tablets of Aspirin + K (D) PT
Prescription:
the preparation process comprises the following steps: sieving aspirin and K (D) PT with a 100-mesh sieve, sieving microcrystalline cellulose and low-substituted hydroxypropyl cellulose with a 80-mesh sieve, weighing aspirin and K (D) PT with the prescribed amount, uniformly mixing with the microcrystalline cellulose and the low-substituted hydroxypropyl cellulose, adding 8% hydroxypropyl methyl cellulose solution for granulation, drying at 40 ℃, sieving with a 16-mesh sieve for size stabilization, adding magnesium stearate with the prescribed amount into the dry granules for uniform mixing, mixing and pressing for 1000 tablets to obtain the aspirin-low-substituted hydroxypropyl cellulose tablet.
EXAMPLE 2 preparation of tablets of Aspirin + K (D) PT
Prescription:
the preparation process comprises the following steps: sieving aspirin and K (D) PT with a 100-mesh sieve, sieving carboxymethylcellulose calcium and low-substituted hydroxypropyl cellulose with a 80-mesh sieve, weighing aspirin and K (D) PT with the prescribed amount, uniformly mixing with microcrystalline cellulose and low-substituted hydroxypropyl cellulose, adding 8% hydroxypropyl methylcellulose solution for granulation, drying at 40 ℃, sieving with a 16-mesh sieve for granulation, adding magnesium stearate with the prescribed amount into the dry granules for uniform mixing, and pressing into 1000 tablets to obtain the aspirin and K (D) PT tablet.
EXAMPLE 3 preparation of Aspirin + K (D) PT capsules
Prescription:
the preparation process comprises the following steps: mixing aspirin, K (D) PT, and lactose at room temperature, adding 10% starch slurry to make soft mass, sieving with 18 mesh sieve to make wet granule, drying at 60 deg.C, sieving with 16 mesh sieve to make granule, and filling 1000 empty capsule shells with the granule.
EXAMPLE 4 tablet preparation of naproxen + K (D) PT
Prescription:
the preparation process comprises the following steps: sieving naproxen and K (D) PT with a 100-mesh sieve, sieving microcrystalline cellulose and low-substituted hydroxypropyl cellulose with a 80-mesh sieve, weighing naproxen and K (D) PT with the prescription amount, uniformly mixing with the microcrystalline cellulose and the low-substituted hydroxypropyl cellulose, adding 8% hydroxypropyl methyl cellulose solution for granulation, drying at 40 ℃, sieving with a 16-mesh sieve for size stabilization, adding stearic acid with the prescription amount into the dry granules for uniform mixing, mixing and pressing for 1000 tablets to obtain the tablet.
EXAMPLE 5 preparation of naproxen + K (D) PT capsules
Prescription:
the preparation process comprises the following steps: mixing naproxen, K (D) PT and lactose at room temperature, adding 10% starch slurry to prepare soft mass, sieving with 18 mesh sieve to prepare wet granules, drying at 60 deg.C, sieving with 16 mesh sieve to obtain dry granules, and filling the granules into 1000 empty capsule shells.
EXAMPLE 6 preparation of granules of celecoxib + K (D) PT
Prescription:
the preparation process comprises the following steps: sieving celecoxib and K (D) PT with 100 mesh sieve, mixing with lactose, carboxymethylcellulose calcium, and crospovidone, adding water, stirring, granulating, drying, sieving with 20 mesh sieve, adding magnesium stearate, sieving with 14 mesh sieve, granulating, drying at 60 deg.C, sieving with 14 mesh sieve, and granulating.
EXAMPLE 7 preparation of celecoxib + K (D) PT capsules
Prescription:
the preparation process comprises the following steps: mixing celecoxib, K (D) PT and lactose at room temperature, adding 10% starch slurry to prepare soft material, sieving with 18 mesh sieve to prepare wet granules, drying at 60 ℃, sieving dry granules with 16 mesh sieve to complete granules, and filling the granules into 1000 empty capsule shells to obtain the celecoxib-lactose-containing capsule.
EXAMPLE 8 preparation of tablets of diclofenac + K (D) PT
Prescription:
the preparation process comprises the following steps: sieving diclofenac and K (D) PT with 100 mesh sieve, mixing with lactose, ethyl cellulose and crospovidone, adding water, stirring, granulating, drying, sieving with 20 mesh sieve, adding magnesium stearate, sieving with 14 mesh sieve, granulating, drying at 60 deg.C, adding stearic acid, mixing, and tabletting to obtain 1000 tablets.
EXAMPLE 9 preparation of diclofenac + K (D) PT granules
Prescription:
diclofenac acid 1g
K(D)PT 0.8g
Dextrin 450g
The preparation process comprises the following steps: mixing diclofenac, K (D) PT and dextrin at room temperature, adding 40% ethanol to make soft mass, sieving with 10 mesh sieve to make wet granule, drying at 60 deg.C, sieving with 20 mesh sieve, and granulating.
Example 10 study of therapeutic Effect of the composition of the present invention on mouse with rheumatoid arthritis
1 materials of the experiment
1.1 drugs and reagents
Aspirin, naproxen tablets, celecoxib, diclofenac, complete Freund's adjuvant, an IL-l beta detection kit, an IL-6 detection kit and FITC-DT.
1.2 Experimental animals
SD rats, 8 weeks old, body weight 180-.
1.3 instruments
SA-YLS-7C toe volume measuring instrument and multifunctional fluorescent enzyme labeling instrument.
2. Experimental methods
2.1 establishment of rheumatoid arthritis model
The rat is placed in a self-made aluminum alloy glass molding box, the humidity in the box is controlled by an ultrasonic atomizer, ice blocks are increased, the environmental temperature in the box is controlled to be 6 +/-2 ℃, the humidity is 75% -95%, the wind power of an electric fan is set to be high-grade, and the time is continuous for 12 hours. All rats needing molding are placed in the wind, cold and wet environment for 20d (12h/d) (20: 00-8: 00). On day 21, the left hind paw was disinfected with 75% alcohol and then injected with Freund's complete adjuvant 0.15 mL/mouse. And 3d, the acute inflammatory swelling of the ankle part is observed for 24h, and red swelling or inflammatory nodules are observed in the forelimb or the contralateral limb or even the ear and the tail part after 48 h.
2.2 study of the Effect of different amounts of the composition on the anti-rheumatic Effect
The rats which are successfully molded are taken and raised in cages, 4 rats are raised in each cage, the room temperature is kept at about 21 ℃, and ventilation is good. The rheumatoid arthritis model rats were randomly grouped into 8 rats each for 16 weeks of intervention treatment. Another age-matched normal rat was used as a blank control group. The method comprises the following specific steps:
(1) a blank control group (group A), wherein the stomach is perfused with 10ml of normal saline;
(2) model control group (group B), 10ml normal saline lavage;
(3) k (D) PT group (group C), K (D) PT 1mg, dissolving in 10ml physiological saline, and intragastrically administering;
(4) aspirin group (group D), aspirin 14mg, dissolved in 10ml normal saline, and administered by intragastric administration;
(5) naproxen group (group E), naproxen 1.9mg, dissolved in 10ml normal saline, gavage;
(6) celecoxib group (F group), wherein 1.9mg of celecoxib is dissolved in 10ml of normal saline and is perfused into the stomach;
(7) diclofenac group (G group), diclofenac 0.25mg, dissolved in 10ml normal saline, and administered by intragastric administration;
(8) the group of example 1, the tablet of example 1 is 100mg, dissolved in 10ml of normal saline, and administered by gavage;
(9) example 2 group, example 2 tablet 100mg, dissolved in 10ml normal saline, and gavage;
(10) example 3 group, example 3 capsule 100mg, dissolved in 10ml normal saline, and perfused;
(11) example 5 group, example 5 Capsule 100mg, dissolved in 10ml normal saline for intragastric administration;
(12) example 6 group, example 6 granules 100mg, dissolved in 10ml of normal saline for intragastric administration;
(13) EXAMPLE 8 group, EXAMPLE 8 tablet 100mg, dissolved in 10ml of physiological saline for intragastric administration;
the drugs of the experimental groups except the control group are treated by the same volume of normal saline to prepare liquid for testing. Gavage administration was performed 1 time per day for 20 consecutive days. The left toe volume of each group of rats was measured using SA-YLS-7C toe volume measuring instrument, blood was taken and serum IL-l β and IL-6 were measured.
2.3 intestinal permeability test with FITC-DT
100g/L chloral hydrate (0.2 mL/rat) is subjected to intraperitoneal injection anesthesia, then 4-5 cm of small intestine is selected at a position 2cm away from the ileocecal part and two ends of the intestinal canal are ligated, and the condition that mesenteric blood flow is normal needs to be emphasized. 0.2mL of FITC-DT was injected into the ligated intestine using a skin test needle, the rat was incubated for 25min and then the liver was removed, the same weight of liver tissue was weighed and ground on ice using a homogenizer and diluted with 0.2g/mL of 5mL PBS buffer. Centrifuge at 1800r/min for 40 min. And (4) taking the supernatant, measuring fluorescence values (excitation wavelength of 480nm and emission wavelength of 530nm) by using a multifunctional fluorescence microplate reader, and carrying out data analysis and statistics.
2.4 statistical analysis
Statistical analysis of the experimental data with SPSS18.0 software as mean. + -. standard deviation
Representing, pairwise comparison between groups by t-test, P<0.05 indicates that the difference is statistically significant.
3. Results
3.1 Effect of different treatment methods on the degree of swelling of the joints of rats in rheumatoid arthritis model
The left toe volume of each group of rats was measured using SA-YLS-7C toe volume measuring instrument, and the average was taken 3 times. The results are shown in Table 1. Compared with the blank control group, the foot sole and the ankle of the rats in other groups have obvious acute inflammation and red swelling, and the volume of the foot sole is obviously increased (P is less than 0.01) compared with that of the rats in the blank group, thereby indicating that the molding is successful. Compared with the rats in the model group, the joint swelling degree of the rats in the K (D) PT group (group C) is not obviously changed (P is more than 0.05), the swelling degree of the rats in the other treatment groups is improved (P is less than 0.01), and the joint swelling degree of the rats in the treatment groups is not obviously changed (P is more than 0.05). And (4) prompting: the non-steroidal anti-inflammatory drug and K (D) PT are combined for use, so that the local swelling of RA rats can be effectively improved, and the volume value of foot soles is reduced.
TABLE 1 comparison of toe volumes of rats in each group
Note: compared with the blank control group (group A),aP<0.05，aaP<0.01; compared with the model control group (group B),bP<0.05，bbP<0.01; compared with the K (D) PT group (group C),cP<0.05，ccP<0.01; compared with the aspirin group (group D),dP<0.05，ddP<0.01; in comparison with the naproxen group (group E),eP<0.05，eeP<0.01; compared with the celecoxib group (group F),fP<0.05，ffP<0.01; compared with the diclofenac group (group G),gP<0.05，ggP<0.01。
3.2 measurement of levels of inflammatory factors in serum
Rat serum was taken to detect the influencing factors according to the kit instructions and the results are shown in table 2. Compared with the blank control group, the IL-l beta and IL-6 in the serum of rats in the rest groups are obviously increased (P < 0.05). Compared with rats in the model group (group B), the rats in the K (D) PT group (group C) have the tendency of down-regulating IL-l beta and IL-6 in the serum, but the down-regulation is not obvious (P is more than 0.05), and the IL-l beta and IL-6 in the serum of the rats in the other treatment groups are obviously reduced (P is less than 0.01); compared with aspirin group (group D), IL-l beta and IL-6 in rat serum of groups of example 1, example 2 and example 3 are all significantly reduced (P < 0.01); compared with the naproxen group (group E), the IL-l beta and IL-6 in the serum of rats in the group of example 5 are both significantly reduced (P < 0.01); compared with the celecoxib group (group F), IL-l beta and IL-6 in the serum of rats in the group 6 are obviously reduced (P < 0.01); both IL-l β and IL-6 were significantly reduced in the serum of rats of the example 8 group compared to the diclofenac group (group G) (P < 0.01). The results indicate that K (D) PT has no obvious down-regulation effect on IL-l beta and IL-6 inflammatory factors caused by rheumatoid arthritis, and the non-steroidal anti-inflammatory drug combined with K (D) PT for treating rheumatoid arthritis has obvious inhibition effect on IL-l beta and IL-6, and the anti-inflammatory effect is better than that of the non-steroidal anti-inflammatory drug used alone for treating.
TABLE 2 expression levels of inflammatory factors in the serum of rheumatoid arthritis rats
Note: compared with the blank control group (group A),AP<0.05，AAP<0.01; compared with the model control group (group B),BP<0.05，BBP<0.01; compared with the K (D) PT group (group C),CP<0.05，CCP<0.01; compared with the aspirin group (group D),DP<0.05，DDP<0.01; naproxen group(group E) comparison of the results,EP<0.05，EEP<0.01; in comparison with the celecoxib group (group F),FP<0.05，FFP<0.01; compared with the diclofenac group (group G),GP<0.05，GGP<0.01。
3.3 Effect of each treatment on rat intestinal mucosal permeability
FITC-DT is used as a detection probe for detecting permeability of intestinal mucosa. FITC-DT is a macromolecular fluorescent marker that can only penetrate blood vessels through mucosal lesions and be absorbed when the intestinal mucosal barrier is damaged. Therefore, the permeability change of the intestinal mucosa can be reflected by detecting Relative Fluorescence Units (RFU) of liver tissue, and the results are shown in Table 3. Compared with the blank control group (group A), the liver tissue FITC-DT content of the rats in the model control group (group B) is not significantly different (P >0.05), reflecting that the intestinal mucosa permeability is not significantly different. Compared with the model control group (group B), the liver tissues of rats in the treatment group aspirin group (group D), the naproxen group (group E), the celecoxib group (group F) and the diclofenac group (group G) have obviously increased FITC-DT content (P is less than 0.01), and the intestinal mucosa permeability of other groups is obviously increased. RFU values were significantly down-regulated in example 1, example 2, example 3, i.e. aspirin in combination with k (D) PT treatment group (P <0.01) compared to aspirin group (group D), and FITC-DT content was not significantly different (P >0.05) compared to model control group (group B); RFU values were significantly downregulated in the example 5 group, naproxen combined with k (d) PT treated group (P <0.01) compared to the naproxen group (group E) and there was no significant difference in FITC-DT content (P >0.05) compared to the model control group (group B); RFU values were significantly down-regulated (P <0.01) in the celecoxib-combined k (d) PT-treated group of example 6 compared to the celecoxib group (group F), and FITC-DT content was not significantly different (P >0.05) compared to the model control group (group B); compared with the diclofenac group (group G), the RFU value of the diclofenac and K (D) PT treatment group in the example 8 group is obviously reduced (P <0.01), and compared with the model control group (group B), the FITC-DT content is not obviously different (P > 0.05). The results suggest that the combination of the NSAID and K (D) PT treatment can effectively reduce the side effect of the NSAID on the intestinal tract
TABLE 3FITC-DT content in rat liver tissue
Note: compared with the blank control group (group A),1P<0.05，11P<0.01; compared with the model control group (group B),2P<0.05，22P<0.01; compared with the aspirin group (group D),3P<0.05，33P<0.01; in comparison with the naproxen group (group E),4P<0.05，44P<0.01; in comparison to celecoxib group 1 (group F),5P<0.05，55P<0.01; compared with the diclofenac group (group G),6P<0.05，66P<0.01。
the results show that the combination of the non-steroidal anti-inflammatory drug and the K (D) PT in the treatment of the rheumatoid arthritis can effectively improve the joint swelling caused by the rheumatoid arthritis, the inhibition on inflammatory factors is better than that of the non-steroidal anti-inflammatory drug which is used alone with effective dose, and simultaneously, the use dose of the non-steroidal anti-inflammatory drug can be reduced, the side effect is reduced, and the safety of medication and the compliance of patients are improved.
The above description of the embodiments is only for the purpose of assisting understanding of the method of the present invention and the core idea thereof, and should not be construed as limiting the present invention.
Claims (4)
1. A pharmaceutical composition for treating rheumatoid arthritis, said pharmaceutical composition comprising: non-steroidal anti-inflammatory drugs, k (d) PT; wherein the content of the first and second substances,
the weight ratio of the non-steroidal anti-inflammatory drug to the K (D) PT is (0.3-20): 1;
the non-steroidal anti-inflammatory drug is selected from aspirin, acetaminophen, indomethacin, naproxen, naproxone, diclofenac, ibuprofen, nimesulide, rofecoxib and celecoxib.
2. The pharmaceutical composition of claim 1, wherein: the pharmaceutical composition is an oral preparation.
3. The pharmaceutical composition of claim 2, wherein: the oral preparation is selected from one of tablets, granules, capsules and solutions.
4. The pharmaceutical composition of claim 2, wherein: the auxiliary materials of the oral preparation are selected from one or more of starch, pregelatinized starch, starch slurry, dextrin, microcrystalline cellulose, vitamin E, hydroxypropyl methyl cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose calcium, polyethylene glycol (PEG), sodium carboxymethyl cellulose, methyl cellulose, ethyl cellulose, mannitol, lactose, polyvinylpyrrolidone (PVP), cross-linked polyvinylpyrrolidone, magnesium stearate, talcum powder, superfine silica gel powder, sodium bicarbonate, sodium carbonate and enteric coating powder.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008052033A2 (en) * | 2006-10-25 | 2008-05-02 | Mcneil-Ppc, Inc. | Ibuprofen composition |
| CN101773465A (en) * | 2010-01-19 | 2010-07-14 | 南京泛太化工医药研究所 | Polymer micelle medicine carrying system using amino acid as stabilizing agent |
| WO2013041719A1 (en) * | 2011-09-23 | 2013-03-28 | Westfaelische Wilhelms-Universitaet Muenster | Tripeptide kdpt for antiapoptotic treatment |
| CN103585164A (en) * | 2013-11-08 | 2014-02-19 | 海南合瑞制药股份有限公司 | Celecoxib solid composition with increased dissolution rate, and preparation method and application thereof |
| CN104379177A (en) * | 2012-03-20 | 2015-02-25 | 赫里克斯生物医疗公司 | Short antimicrobial lipopeptides |
| CN105744945A (en) * | 2013-11-07 | 2016-07-06 | 奥古斯特沃尔夫博士有限两合公司-医药 | Storage stable lyophilized tripeptide formulations |
| CN106267209A (en) * | 2016-07-18 | 2017-01-04 | 苏州朗易生物医药研究有限公司 | Low dosage non-steroidal anti-inflammatory class pharmaceutical composition and preparation technology thereof |
-
2018
- 2018-10-14 CN CN201811193184.2A patent/CN111035764B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008052033A2 (en) * | 2006-10-25 | 2008-05-02 | Mcneil-Ppc, Inc. | Ibuprofen composition |
| CN101773465A (en) * | 2010-01-19 | 2010-07-14 | 南京泛太化工医药研究所 | Polymer micelle medicine carrying system using amino acid as stabilizing agent |
| WO2013041719A1 (en) * | 2011-09-23 | 2013-03-28 | Westfaelische Wilhelms-Universitaet Muenster | Tripeptide kdpt for antiapoptotic treatment |
| CN104379177A (en) * | 2012-03-20 | 2015-02-25 | 赫里克斯生物医疗公司 | Short antimicrobial lipopeptides |
| CN105744945A (en) * | 2013-11-07 | 2016-07-06 | 奥古斯特沃尔夫博士有限两合公司-医药 | Storage stable lyophilized tripeptide formulations |
| CN103585164A (en) * | 2013-11-08 | 2014-02-19 | 海南合瑞制药股份有限公司 | Celecoxib solid composition with increased dissolution rate, and preparation method and application thereof |
| CN106267209A (en) * | 2016-07-18 | 2017-01-04 | 苏州朗易生物医药研究有限公司 | Low dosage non-steroidal anti-inflammatory class pharmaceutical composition and preparation technology thereof |
Non-Patent Citations (1)
| Title |
|---|
| α-MSH related peptides: a new class of anti-inflammatory and immunomodulating drugs;Thomas A Luger等;《Annals of the rheumatic diseases》;20071130;第66卷;文章摘要部分 * |
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