CN101439021A - Compound diclofenac sodium, methopterin flexible lipidosome and preparation method thereof - Google Patents
Compound diclofenac sodium, methopterin flexible lipidosome and preparation method thereof Download PDFInfo
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- CN101439021A CN101439021A CNA2007101684709A CN200710168470A CN101439021A CN 101439021 A CN101439021 A CN 101439021A CN A2007101684709 A CNA2007101684709 A CN A2007101684709A CN 200710168470 A CN200710168470 A CN 200710168470A CN 101439021 A CN101439021 A CN 101439021A
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- methotrexate
- methopterin
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- diclofenac
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Abstract
The invention provides compound diclofenac sodium, a methotrexate flexible liposome and a preparation method. The invention has the components of diclofenac ranged from 0.5 g to 3.8 g, methotrexate ranged from 0.01 g to 2.0 g, phospholipid ranged from 0.5 g to 8.0 g, sodium cholate ranged from 0.5 g to 3.0 g, a latent solvent ranged from 5.0 g to 20.0 g and the remainder which is phosphate buffer (pH is equal to 7.2). After being heated, dissolved, mixed and stirred, the components can be filtered through ultrasonic treatment with 5 min to 10 min. The flexible liposome can be directly used for skin affected part of a human body, has the actions of analgesia and therapy on rheumatic arthritis, rheumatoid arthritis, various non-articular inflammations, skin cancer, breast cancer, ovarian cancer and osteosarcoma, and overcomes the problem that the prior identical drug is needed to be orally taken to be easy to stimulate intestines and stomach or have the toxic side effect. The invention has the advantages of rapid effect, favorable percutaneous absorption and convenient use.
Description
Technical field
The present invention relates to a kind of externally applied anti-inflammation analgesia and flexible lipidosome that improves immunologic function and preparation method thereof, relate to a kind of compound diclofenac natrium, methopterin flexible lipidosome and preparation method thereof specifically.
Background technology
At present, at the clinical treatment rheumatoid arthritis, osteoarthritis, the scorching various soft tissue injurys of tetanic property marrow post, lupus erythematosus, toothache, dysmenorrhea and cancer, postoperative pain and suppress cell proliferation by antiinflammatory action and treat acute leukemia, chorionic epithelioma, malignant mole, diseases such as osteosarcoma adopt diclofenac sodium and methotrexate medicine more, be injection but these two kinds of medicines have gone on the market, tablet and suppository, after by oral or injection, very easily cause untoward reaction and side effect, occur feeling sick as gastrointestinal side effect, vomiting, stomachache, diarrhoea; Liver function injury comprises that jaundice, alaninyl are pass on and moves enzyme, alkaline phosphatase, Y-glutamyl transpeptidase etc. and increase; The low phenomenon of curative effect can appear in life-time service, and may cause acute interstitial pneumonia or hepatic insufficiency, infringement renal function or sexual function etc.
Summary of the invention
It is principal agent with diclofenac sodium, methotrexate that one of purpose of the present invention is to provide a kind of, with lecithin, sodium cholate is the film material, with the phosphate buffer is solvent, the compound diclofenac natrium effective, that toxicity is low, methopterin flexible lipidosome, can be directly used in the affected part of human body skin, have significant analgesia and therapeutical effect.
The present invention includes diclofenac sodium, methotrexate and sodium cholate, its concrete component is: diclofenac sodium 0.5～3.8 gram, methotrexate 0.01～2.0 gram, phosphatidase 10 .5～8.0 grams, sodium cholate 0.5～3.0 gram, cosolvent 5.0～20.0 grams, phosphate buffer surplus.
Described phospholipid is to incubate phospholipid, cephalin, soybean phospholipid or synthetic phospholipid.
Described latent solvent Liu is dehydrated alcohol or glycerol.
The pH value of described phosphate buffer is 7.2.
Another object of the present invention is to provide a kind of method for preparing above-mentioned flexible lipidosome: its concrete scheme is: after getting phospholipid, sodium cholate, cosolvent component, heating for dissolving, adding diclofenac sodium, methotrexate, phosphate buffer stir fast, supersound process 5-10 minutes, with 0.45 μ m filtering with microporous membrane, promptly get flexible lipidosome.
In the technical solution of the present invention: diclofenac sodium and methotrexate are analgesia and antiphlogistic medicine main body, phospholipid is the main film material that constitutes liposome, it is the basic substance that forms the liposome bilayer, and itself also has very important physical function, formed artificial membrane is easily by the body digest and decompose, the adding of sodium cholate can change the composition of immobilized artificial membrane, make of the see through ability enhancing of the lipoid collective of formation to skin, more medicine can be brought in the body, and the adding of cosolvent, increased the dissolubility of medicine in carrier, more favourable human body is to the absorption of medicine.
Can directly act on the affected part of human body skin during the clinical use of the present invention, characteristic in conjunction with transdermal administration, can give full play to the characteristic of diclofenac sodium and two kinds of medicines of methotrexate, have anti-inflammatory analgesic and improve the immunologic function remarkable efficacy, overcome many shortcomings that existing diclofenac sodium and methotrexate oral medicine cause side effect and untoward reaction easily.
The present invention has following effect through test:
1, transdermal test in vitro test
Corium Mus is loaded on the Franz diffusion cell, and stratum corneum side is to supply chamber, and skin corium is coated the horny layer surface towards accepting the pond with the present invention, and filtrate is adopted the high effective liquid chromatography for measuring sample concentration, the results are shown in subordinate list:
By above-mentioned subordinate list as seen, diclofenac sodium of the present invention, methotrexate compound recipe flexible lipidosome transdermal are functional.
2, clinical observation on the therapeutic effect
A, case select this test according to Americanism damp disease association rheumatoid arthritis criteria for classification in 1987, select to meet patient's 44 examples of rheumatoid arthritis (rhematoid arthritis, R A) diagnostic criteria, be divided into treatment at random and organize 24 examples, male's 9 examples, women's 15 examples, 23～70 years old age.Year mean age (61 ± 9.7).Matched group 20 examples, male's 7 examples, women's 13 examples, 19～70 years old age, year mean age (52 ± 8.8).Two groups of courses of disease 2 months～350 months.All not selected to drug allergy person, anemia of pregnant woman and women breast-feeding their children.
B, Therapeutic Method treatment group external diclofenac sodium flexible lipidosome gel, each an amount of (it is about 0.5～1.0g) to look joint each joint medication of size, directly embrocates the affected part, tid.Matched group is worn fragrant sheet, each 75mg.Two groups were for 4 weeks is a course of treatment, stop using during the treatment other Therapeutic Method and medicine, and observe its symptom and sign and curative effect, the record result.
C, curative effect judging standard write down stiff time in morning, arthralgia index with reference to " rheumatoid arthritis diagnosis guide (draft) " diagnostic criteria according to two groups of patient treatments front and back during the 4th week, the articular pain number, arthroncus number, the function of joint index evaluation curative effects such as degree, degree of fatigue of being obstructed.Promptly be divided into produce effects: clinical symptoms and sign and lab index are improved more than 70% after the course of treatment; Effectively: clinical symptoms and sign and lab index improve 50%～70%; Little effect: clinical symptoms and sign and lab index improve 20%～50%; Invalid: clinical symptoms and sign and lab index are improved below 20%.With micro-and effective calculating total effective rate.
24 examples are organized in D, therapeutic outcome treatment, produce effects 10 examples (42%), effective 10 examples (42%), little effect 3 examples (12%), invalid 1 example (4%), total effective rate 83%.Matched group 20 examples, produce effects 9 examples (45%), effective 7 examples (35%), little effect 3 examples (15%), invalid 1 example (5%), total effective rate 80%.Two groups of total effective rates are through x
2Check has significant difference (P＜0.05).
The specific embodiment
The following stated embodiment understands the present invention in detail.In the following embodiments, be population unit all with 100 grams.
Embodiment 1:
Get incubate phosphatidase 10 .7 gram, sodium cholate 1.8 grams, dehydrated alcohol 10 gram heating for dissolving after, adding diclofenac sodium 0.8 gram, methotrexate 0.02 gram, pH value are 7.2 phosphate buffer 86.68 grams, stir fast, ultrasonic Treatment 6 minutes, adopt 0.45 μ m filtering with microporous membrane, promptly get flexible lipidosome..
Embodiment 2:
After getting cephalin 1.5 grams, sodium cholate 0.6 gram, glycerol 11 gram heating for dissolving, adding diclofenac sodium 2 grams, methotrexate 1.2 grams, pH value are 7.2 phosphate buffer 81.7 grams, stirring fast, ultrasonic Treatment 8 minutes, adopt 0.45 μ m filtering with microporous membrane, promptly get flexible lipidosome..
Embodiment 3:
After getting soybean phospholipid 7.5 grams, sodium cholate 3 grams, dehydrated alcohol 15 gram heating for dissolving, adding diclofenac sodium 2.5 grams, methotrexate 0.09 gram, pH value are 7.2 phosphate buffer 68.91 grams, stir fast, ultrasonic Treatment 5 minutes, adopt 0.45 μ m filtering with microporous membrane, promptly get flexible lipidosome..
Embodiment 4:
After getting synthetic phospholipid 3.2 grams, sodium cholate 1.6 grams, glycerol 6 gram heating for dissolving, adding diclofenac sodium 1.4 grams, methotrexate 1.6 grams, pH value are 7.2 phosphate buffer 82.2 grams, stir fast, ultrasonic Treatment 10 minutes, adopt 0.45 μ m filtering with microporous membrane, promptly get flexible lipidosome..
Embodiment 5:
After getting soybean phospholipid 6.2 grams, sodium cholate 0.9 gram, dehydrated alcohol 6 gram heating for dissolving, adding diclofenac sodium 0.6 gram, methotrexate 0.7 gram, pH value are 7.2 phosphate buffer 80.6 grams, stir fast, ultrasonic Treatment 9 minutes, adopt 0.45 μ m filtering with microporous membrane, promptly get flexible lipidosome..
Embodiment 6:
Get incubate phosphatidase 12 .1 gram, cholic acid 2.2 grams, glycerol 19 gram heating for dissolving after, adding diclofenac sodium 3.6 grams, methotrexate 1.8 grams, pH value are 7.2 phosphate buffer 65.3 grams, stirring fast, ultrasonic Treatment 7 minutes, adopt 0.45 μ m filtering with microporous membrane, promptly get flexible lipidosome..
Claims (5)
1, a kind of compound diclofenac natrium, methopterin flexible lipidosome comprise diclofenac sodium, methotrexate and sodium cholate, it is characterized in that: the component in described per 100 gram flexible lipidosomes is:
Diclofenac sodium 0.5～3.8 gram
Methotrexate 0.01～2.0 gram
Phosphatidase 10 .5～8.0 grams
Sodium cholate 0.5～3.0 gram
Cosolvent 5.0～20.0 grams
Phosphate buffer (pH is 7.2) surplus.
2, a kind of compound diclofenac natrium according to claim 1, methopterin flexible lipidosome is characterized in that: described phospholipid is to incubate phospholipid, cephalin, soybean phospholipid or synthetic phospholipid.
3, a kind of compound diclofenac natrium according to claim 1, methopterin flexible lipidosome is characterized in that: described cosolvent is dehydrated alcohol or glycerol.
4, a kind of compound diclofenac natrium according to claim 1, methopterin flexible lipidosome is characterized in that: the pH value of described phosphate buffer is 7.2.
5, a kind of preparation method that is used for claim 1 compound diclofenac natrium, methopterin flexible lipidosome, it is characterized in that: after getting phospholipid, sodium cholate, cosolvent component, heating for dissolving, adding diclofenac sodium, methotrexate, phosphate buffer stir fast, supersound process 5-10 minutes, use the 0.45mn filtering with microporous membrane, promptly get flexible lipidosome.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101684709A CN101439021A (en) | 2007-11-20 | 2007-11-20 | Compound diclofenac sodium, methopterin flexible lipidosome and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101684709A CN101439021A (en) | 2007-11-20 | 2007-11-20 | Compound diclofenac sodium, methopterin flexible lipidosome and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN101439021A true CN101439021A (en) | 2009-05-27 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2007101684709A Pending CN101439021A (en) | 2007-11-20 | 2007-11-20 | Compound diclofenac sodium, methopterin flexible lipidosome and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102600079A (en) * | 2012-03-19 | 2012-07-25 | 吉林大学 | Nystatin flexible liposome as well as gel and preparation method of nystatin flexible liposome |
-
2007
- 2007-11-20 CN CNA2007101684709A patent/CN101439021A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102600079A (en) * | 2012-03-19 | 2012-07-25 | 吉林大学 | Nystatin flexible liposome as well as gel and preparation method of nystatin flexible liposome |
| CN102600079B (en) * | 2012-03-19 | 2013-11-13 | 吉林大学 | Nystatin flexible liposome as well as gel and preparation method of nystatin flexible liposome |
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Open date: 20090527 |