CN86104141A - The preparation method of polyacrylic esters containing medicine of slow release formulation - Google Patents
The preparation method of polyacrylic esters containing medicine of slow release formulation Download PDFInfo
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- CN86104141A CN86104141A CN86104141.0A CN86104141A CN86104141A CN 86104141 A CN86104141 A CN 86104141A CN 86104141 A CN86104141 A CN 86104141A CN 86104141 A CN86104141 A CN 86104141A
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- interpolymer
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Abstract
A kind of polyacrylate(s) that contains, the medicament slow release preparation methods, be in prior preparation method, to add to the great carbohydrate of water solubility with irradiation to cause the replacement novel method of chemical trigger monomer in the past, make product become mesh-structured, and initiator and the harmful influence of promotor that may be residual when reducing chemical process and causing.This novel material can be widely used in osteopathy such as osteomyelitis, big area abscess, soft tissue infection, and through the clinical use of various big hospital, operation obtains top grade and reaches more than 90%, and good level reaches 100%.
Description
The invention relates to the preparation method who contains polyacrylic esters containing medicine of slow release formulation, specifically be by the polyacrylate(s) powder, emulsified monomer (methyl methacrylate), oxide compound, salt, carbohydrate, medicine cause under certain irradiation dose, make monomer activation back generate the novel method that contains mesh-structured polyacrylic esters containing medicine of slow release formulation.
As everyone knows, acrylic polymer has good Bc, is widely used as dental material always.Buchholg in 1970 and Engolbiecht join gentamicin in the bone cement, and the prosthese treatment operation that is used for whole coxa substitution and infection is succeedd.When but the heeling-in of bone cement need be performed the operation under the operative failure situation for the second time, the bone cement that residues in the bone chamber was difficult to remove, and often influences mechanical effect.
2511122 German patent specification that on August 6th, 1977 announced are pointed out to add Nacl, KBr, NaBr, Kcl as filler in a kind of gentamicin bone cement, can increase the burst size and the concentration of gentamicin.The desired protection interests of this patent are: add the 25mg dibenzoyl peroxide in the 4.75 gram acrylic ester copolymerization body powder, the Ursol D and the 66ppm hydroquinone solution that contain 2 parts of weight percents in the gentamicin sulphate of 250mg purified KBr, 103mg and the 2.5ml monomer also can add 0.5g Zno
2Or BaSo
4
Owing to added Nacl or KBr in the prescription, can make drug release concentration improve several times, this may be included in salt in the material and cause uneven surface after water-soluble, increased contact surface, even having formed surface hole, the medicine that makes part be in the close state of envelope has an opportunity to discharge with extraneous the contact.
The medicament slow release material that gets by above-mentioned patent system, be immersed in the distilled water, through 2 hours, 6 hours, the next day after get its soak solution, observe its medicine (garamycin sulfate) release conditions, test is according to two 537 pages of described methods of Pharmacopoeia of People's Republic of China " nineteen eighty-three version ", make the color reaction of garamycin sulfate with triketohydrindene hydrate, find that reaction is not obvious, this kind Yao Wu Chuan material burst size is described seldom.
Activation by the described method monomer whose of above-mentioned patent methyl methacrylate simultaneously must add superoxide such as benzoyl peroxide etc., promotor phenyl amines and derivative thereof.Though dosage is few, and chemical reaction has taken place, can not get rid of residue in addition.These residues of not participating in reaction are known from experience the generation adverse influence to the people.
The objective of the invention is to make filler by adding carbohydrate, its solubleness in human body is improved, it is mesh-structured that polymethyl acrylate class medicament slow release material is generated, and increases the medicine amount of depositing in and improve release concentration.The present invention simultaneously adopts irradiation to cause to replace chemistry to cause.Can get rid of above-mentioned two kinds of chemical substances like this and may produce injurious effects human body.
Manufacture method of the present invention is to be main raw material with esters of acrylic acid polymer or interpolymer.As methyl methacrylate and butyl acrylate interpolymer, after being ground into fine powder and the blend of filler medicine and.Filler has oxide compound such as zinc oxide, zirconium white, calcium phosphate, barium sulfate etc.; Salt has KBr, NaBr, Kcl, Naci etc.; Carbohydrate has sucrose and glucose etc.; Medicine has garamycin sulfate etc.Each component is composed as follows:
100 parts in interpolymer powder
10～20 parts of oxide compounds
15～20 parts of salts
20～30 parts of carbohydrates
5～8 parts of medicines
The mixed at normal temperatures evenly back of above-mentioned each component is stand-by.
The preparation of emulsified monomer is that methyl methacrylate and sterilized water emulsification in the presence of the dispersion agent emulsifying agent form.
The ratio of monomer and sterilized water is:
100 parts of monomers
10～40 parts of sterilized waters
In order to make emulsified monomer have activity, before emulsification, must carry out irradiation to monomer earlier and cause, the irradiation amount of initiator is 9 * 10
5～1.44 * 10
7La Te.
Before the polyreaction, that the interpolymer for preparing and filler powder and emulsified monomer is mixed.Can be pressed into bead chain shape with mould, also can be made into other shape, then at normal temperatures or under 40～80 ℃, carry out polymerization, in 3 hours, finish polymerization at 20 minutes.
The present invention has following advantage:
1. consider salt in water solubleness less than the candy height, so the present invention is except adding salt, carbohydrate such as sucrose and glucose etc. have also been added, exist with solid under these material normal circumstancess, solubleness is big especially when meeting water, add the medicament slow release material that contains garamycin sulfate that makes behind the carbohydrate, it is immersed in the distilled water, through 2 hours, 6 hours, the next day after get its soak solution again and survey its level of response with the triketohydrindene hydrate color reaction, find soak solution and react much fierce than the medicament slow release material that does not add carbohydrate.This just fully shows that drug release concentration of the present invention is much higher than Deutsches Reichs-Patent.
2. the present invention is not when adding medicine, made bone cement, as be made into a bowl dish shape, polymerizing curable is placed in the water and soaks a couple of days, being filled with water with it then places on the shelf, can find that there is " sweating " phenomenon on its surface, and the bottom has little water droplet to count the spot speed drippage with per minute, this proves also and has formed mesh-structuredly that and communicate with each other in the inside and outside.
The bone cement that the present invention makes soaks in deionized water, changes every day and soaks water, takes out oven dry after seven days, does not oppose than test in soaking exemplar, and through Shanghai photomicrography that Testing Technology Study is done, photo is seen attached Fig. 1 and 2.(the 1st, without the mesh-structured material Photomicrograph before soaking; The 2nd, the Photomicrograph of the mesh-structured material in immersion two weeks back in the water.) can find also that from photo the obtained medicament slow release material internal of the present invention exists many holes, and these holes structure of mesh that almost has been the formation that communicates with each other.
3. another big advantage of the present invention is to cause with irradiation to replace peroxide initiator and phenyl amines and derivative thereof to do promotor, and having got rid of above-mentioned chemical substance residue may be to the disadvantageous effect of human body generation.Bacteria test:
The medicament slow release material of the present invention's preparation, the garamycin sulfate that discharges has very high sterilizing ability, Long March hospital of the No2. University of Medical Sciences of Chinese People's Liberation Army bacterial classification chamber, be placed in the culture dish of the agar that contains activated staphylococcus aureus, discovery has the obvious sterilization effect, obviously occurs aseptic circle around it.
Animal experiment:
The medicament slow release material that the Chinese People's Liberation Army the 193rd army hospital makes the present invention, be implanted in the dog femoral medullary space and test, through several dog test-results, find heeling-in after several days dog just can stand, life is normal, well-grown, and inflammation does not appear in wound circumference, taking-up discovery implant material combines closely with dog limb osseous tissue and is as good as after half a year, and the hole on slow-release material surface is connected with cell.Clinical trial:
Heilongjiang Provincial Hospital's orthopaedics is measured the concentration of the gentamicin that produces in the blood, proves that time of releasing is long, and more stable.Burst size generally remains between 0.45～0.6 μ g/ml, even also be like this after 90 days.
The medicament slow release material of the present invention's preparation has purposes widely, can be used for osteomyelitis, big area abscess, soft tissue infection etc.Orthopaedics clinical application through more than ten hospitals such as Zhongshan affiliated hospital of shanghai medical university, Shanghai Changning District central hospital, Heilongjiang Provincial Hospital, Bangfu City No.2 People's Hospital, Liaoyang City hospital, second the People's Hospitals, Xinxiang, Henan, nearly hundred routine surgery information analyses, effect is remarkable, curative ratio is all more than 90%, and good level reaches 100%.Carry out 19 person-times of clinical applications as Liaoyang City institute of traditional Chinese medicine, Liaoyang City the 19 hospital of Engineering Bureau etc., acute osteomyelitis 4 examples wherein, internal fixation operation postoperative infection 6 examples, open fracture spouts and infects 9 examples, the longest implantation more than 60 day.Analyze above-mentioned 19 routine effects, top grade 14 examples wherein, good level 5 examples, good level accounts for 100%.
Except that adding the medicine, also can add the slow-release material that other material such as spices, agricultural chemicals etc. can make other purposes with the slow-release material of method of the present invention preparation.
Embodiment one:
1. the interpolymer powder mixes is formed
The PMMA(polymethylmethacrylate) 575 part
ZrO
258 parts
The GT(garamycin sulfate) 40 part
53 parts of glucose
Ca
3(PO
4)
274 parts
2.MMA(methyl methacrylate) 1.8 * 10
6Irradiation under the La Te.
Emulsified monomer is formed:
160 parts of monomer M MA
Sterilized water (H
2O) 33 parts
The ratio of interpolymer powdered mixture and emulsified monomer is 1: 2.
Polymerization temperature is 40～60 ℃, and polymerization time is 3 hours.
Embodiment two:
1. the interpolymer powdered mixture is formed:
575 parts of PMMA
ZrO
258 parts
40 parts of GT
53 parts of sucrose
Ca
3(PO
4)
274 parts
2. monomer M MA is 1.44 * 10
7Irradiation under the La Te.
Emulsified monomer is formed:
54 parts of monomer M MA
11 parts of sterilized waters
The ratio of interpolymer mix powder and emulsified monomer is 2: 1.
Polymerization temperature is 60～70 ℃, and polymerization time is 2 hours.
Embodiment three:
1. the comonomer powdered mixture is formed:
100 parts of PMMA
BaSO
410 parts
7 parts of GT
9 parts of sucrose
Ca
3(PO
4)
24 parts
4 parts of Nacl
2. monomer M MA is 1.44 * 10
7Irradiation under the La Te.
Emulsified monomer is formed:
54 parts of monomer M MA
11 parts of sterilized waters
The ratio of interpolymer powdered mixture and emulsified monomer is 1: 3.
Polymerization temperature is 70～80 ℃, and the time is 2 hours.
Embodiment four:
1. the comonomer powdered mixture is formed:
50 parts of PMMA
ZrO
25 parts
3.5 parts of GT
8 parts of glucose
Ca
3(PO
4)
210 parts
2. monomer M MA is 7.2 * 10
6Irradiation under the La Te.
Emulsified monomer is formed:
148 parts of monomer M MA
30 parts of sterilized waters
Emulsified monomer is 1: 3 with the ratio of multipolymer powdered mixture.
Solidification value is under 60～70 ℃, and the time is 3 hours.
Claims (3)
1, a kind of polyacrylate(s) such as methyl methacrylate and butyl acrylate interpolymer powder, medical slow-release material preparation method of oxide filler such as zirconium white, calcium phosphate, barium sulfate, zinc oxide, salt such as Potassium Bromide, Sodium Bromide, Repone K, medicine, emulsified monomer, peroxide initiator, promotor phenyl amines and derivative thereof of containing.It is characterized in that having added in the interpolymer powder water-soluble extremely excellent carbohydrate such as sucrose, glucose etc.The activation of monomer whose is to cause with irradiation, and the polyacrylic esters containing medicine of slow release formulation that is aggregated into has mesh-structured.
2, polyacrylic ester medicament slow release preparation methods as claimed in claim 1 is characterized in that
The ratio of interpolymer powder each component is:
15～20 parts of 10～20 parts of salts of 100 parts of oxide compounds of interpolymer
5～8 parts of 20～30 parts of medicines of carbohydrate
Emulsified monomer, methyl methacrylate with the ratio of sterilized water are:
10～40 parts of 100 parts of sterilized waters of methyl methacrylate
The ratio of interpolymer powdered mixture and emulsified monomer: 3: 1～1: 3
3, the preparation method of polyacrylic esters containing medicine of slow release formulation as claimed in claim 1 or 2 is characterized in that:
(1) monomer irradiation amount of initiator is 9 * 10
5～1.44 * 10
7La Te
(2) after the emulsified monomer after interpolymer powdered mixture and the activation mixes, at normal temperatures or 40～80 ℃ of following polymerizations 20 minutes to 3 hours, goods can become bead chain shape also to can be made into other shape.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 86104141 CN1011288B (en) | 1986-12-25 | 1986-12-25 | Process for manufacturing polyacrylic esters containing medicine of slow release formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 86104141 CN1011288B (en) | 1986-12-25 | 1986-12-25 | Process for manufacturing polyacrylic esters containing medicine of slow release formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN86104141A true CN86104141A (en) | 1988-07-13 |
| CN1011288B CN1011288B (en) | 1991-01-23 |
Family
ID=4802364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 86104141 Expired CN1011288B (en) | 1986-12-25 | 1986-12-25 | Process for manufacturing polyacrylic esters containing medicine of slow release formulation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1011288B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101332311B (en) * | 2007-06-29 | 2012-01-11 | 北京天助畅运医疗技术股份有限公司 | Drug-loaded mesh grid with slow-release function, production method and use thereof |
-
1986
- 1986-12-25 CN CN 86104141 patent/CN1011288B/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101332311B (en) * | 2007-06-29 | 2012-01-11 | 北京天助畅运医疗技术股份有限公司 | Drug-loaded mesh grid with slow-release function, production method and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1011288B (en) | 1991-01-23 |
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