JPH02503205A - Crosslinked hydrophilic copolymers for medical and paramedical applications - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] This invention is suitable for medical and paramedical applications. With respect to products for use in the “Medical use” also includes “veterinary use” and “surgical use,” and “Nogura medical use” means “ It also includes "therapeutic", "dietary" and "life-sustaining foods".

The products mentioned above are mainly of the cross-linked alkaline acrylamide/acrylate type or consists of a hydrophilic copolymer of the cross-linked alkaline vinyl alcohol acrylate type. The following describes the preferred products acrylamide and Acrylic IJ). Copolymers with sodium acrylate and vinyl alcohol with sodium acrylate The present invention will now be described in more detail with respect to the copolymers.

Cross-linked copolymers of acrylamide and sodium acrylate are used in agriculture and adhesives It is well known for its applications in various fields such as industry, and is used as a powder in color photocopying. used. These have the property of gelling in aqueous media and are suitable for powder particle size measurement. According to this, it has the property of absorbing water hundreds of times its own volume. I have to.

All the large companies in the pharmaceutical and other chemical industries, such as Hoechst, Minnesota Mining, DuPont de Nemours Ricoh, Toshi Kogyo, Yasua... Associated with species copolymers.

The present invention is suitable for the use of such products in very diverse industrial fields, viz. Concerning applications in the broad medical and paramedical fields. These copolymers are , has “neutral” properties towards human and animal organisms, which makes this type of It becomes possible to use

The present invention mainly relates to the following basic groups: [wherein R,, R2, R,, R″1, R '2, R1, may be the same or different, and are a hydrogen atom or an atom having 1 to 3 carbon atoms. alkyl group, Me represents an alkali metal, and Z is OH or C　O　N　Hz A medical product characterized by comprising a crosslinked hydrophilic alkaline copolymer of and paramedical products.

Preferred products among the above are R+=Rt=Rs=R ' r-R', -R', -H, Z-CONH. with Me-Na. those of, i.e. , especially copolymers of acrylamide and sodium acrylate, such as: Or R　l−　R　t　−　R　2　−　R’　+　　　　R　　　t　= R's - H, Me = Na and Z-OHO, that is, especially This produces a copolymer of vinyl alcohol and sodium acrylate such as The material conveniently has a diameter in the dry state of 50 to 700 μm, preferably about 250 μm. It can be ground into a powder with an average particle size of . In this form, the product is produced in an aqueous medium. 500-7 of its own volume in the presence of body (water, serum, etc.) or hydrous-alcoholic medium It absorbs 00 times more water and turns into a gel. The process of gelation is maximal and final in aqueous media. It takes 0.5 to 5 minutes for the swelling to occur, so it is relatively quick. Wet powder is It has an average particle size of 450-6200 am, preferably about 3000 μm.

This powder is totally harmless to higher animals, especially mammals and humans. Ma The lethal dose determined for mice is 50 and for rats it is It exceeded 10 hearings per kg of weight. Rabbits that have not been touched or have been rubbed No inflammation was observed after 24 hours in either the chicken skin or the human skin. rabbit's No inflammation in the eyes (no inflammation in the vaginal lining in female dogs, no inflammation in red blood cells in rabbits, dogs, and humans). No hemolytic effects were observed, and no antigenic effects were observed in dogs. Other tests are conducted Described in the example.

The products can therefore be used in the various applications mentioned above.

The first use, which will be explained in detail below, is to reduce morbid hunger and obesity, for example by means of weight loss diets. It is probably of interest to dietitians, as it addresses the full spectrum of nutrition. Especially books The product according to the invention is preferably processed into pills, which are absorbed orally and swell in the stomach. fills the stomach and relieves hunger. As detailed in the Examples below, the product is not absorbed by living organisms and is therefore completely neutral to living organisms. fill the stomach Once the function of relieving hunger by eating food is activated, no changes occur in the intestines. It progresses without any problem and is excreted through natural channels.

In some cases, a very slight laxative effect is observed, which is of no use for the above-mentioned uses. This is a desirable characteristic.

Therefore, it can be incorporated into weight loss diets, in which case the majority of the food and correspondingly reduce the supply of calories or nutritional value. Ru.

In such applications, the products according to the invention are free from the necessities required for processing or for possible pharmaceutical forms. It is taken as is, without any other excipients.

Another use is to provide the products according to the invention with calculated amounts of nutrients necessary for the human organism. Fixes elements (proteins, lipids, glucides, vitamins, mineral salts, trace elements, etc.) The purpose of this food is to constitute a life-sustaining food, which is less appetizing than concentrates or pills. It is tempting and, as mentioned above, has the benefit of eliminating the feeling of hunger indicated by the stomach. exists.

Another important field of use of the products according to the invention is in the field of health care. Therefore Therefore, in the field of health care for health and hygiene, the products according to the invention are in common use. Processed in a suitable manner into bags of woven or non-woven material according to the formula to improve its absorbency. Can be used as a bandage or compress to benefit from its greater liquid absorption capacity. Wear. The same method can be used to make pull-out sheets, diapers for infants or incontinent adults. Ru. It can also be processed into sanitary napkins or pads using appropriate methods. In this case its absorbency will be highly valued.

In the medical field, products impregnated or impregnated with active substances with healing or scar-forming properties are used. Surgical poultices or dry or wet plastics can also be used in a suitable bag. Can be used as a star.

Especially in the medical field, if you are interested in allopathic medicine and homeopathy, you can use the present invention. The product is impregnated with the active substance and deposited on the surface of the organism or brought into the interior of the organism. can be done.

When taken orally, the product protects the intestinal mucosa as a gastric lining, causing gastritis, esophagitis, gastrointestinal Treats and relieves pain in intestinal ulcers, colitis, polyposis, polyps, etc. be able to.

In this same medical field, products according to the invention impregnated with active substances are used for internal topical administration. In this case, the copolymer does not degrade the active substance too quickly. protect the active substance from excess and allow the active substance to reach where it is supposed to act.

For external use, the product according to the invention impregnated with active substances can be applied locally by injection. or can be applied directly to the skin if the active substance acts as a transdermal agent. Wear.

(chemotherapy) or with radioactive elements (radiation therapy), internally or externally. This can also be done by passing it on to the department.

Another important application is when the product is used in the presence of liquid at the beginning of gelation. in the field of plastic surgery. After gelling, the product according to the invention has no effect on living organisms. It provides an excellent maintenance or filling material that is inert and virtually non-biodegradable.

Therefore, the product can be used in the treatment of wrinkles, breast ptosis or as a prosthesis or is used as a plastic insert by injection or incision.

The invention will be better understood with reference to the following non-limiting examples. , these examples demonstrate the non-hazardous nature of the products according to the invention and therefore the aforementioned properties. demonstrating remarkable ease of use in the field, especially in the field of dietetics and health care. It is.

Example 1 excretion through the digestive tract Due to the size of the water-swollen particles, it is highly unlikely that the particles will cross any obstruction in the intestinal wall. few.

To check this, five patients were pre-inflated in 250 d of mineral water. moistened IGETAGEL® copolymer at 10 doses per day. ．． 0 g was administered in two doses for 3 days. This copolymer is produced in Schier, Switzerland. - Available from OMAREX Company of Len ZentH.

Feces were collected for 5 days from day -. Wash this and use a 500m porous filter. Filtered. The collected materials were weighed together at the end of the observation, and the weight recovered was: The details of the five subjects are as follows.

1, 24.6g, 2. 26.3g, 3.　28.2g.

4, 25.1g, 5.　27.2gThe average value of the collected amount was 26.88g This amount, considering handling losses, means that almost all of the product is excreted. Indicates that the

Furthermore, microscopic examination of the particles, their shape and structure shows that they are original in shape and structure. Digestive pathway of 0 particles showed no difference from that, does not alter its properties and structure .

Example 2 Study of the susceptibility of copolymers to enzymes by contacting samples of copolymer particles with water. Maximum swelling was obtained. Disperse the gel with Vortex, so. oo.

A suspension of particles/d was prepared. A sample of this suspension was contacted with the enzymes described below.

Amylase 10.50.100 meq/d Trypsin 1O150 , 100 meq/Id Pepsin 1O150, 100 meq/d suspension The liquid was kept warm in a thermostat at 37°C for 4 hours. After incubation, the collected cells were counted. The number of cells was similar to that of the whole initial sample (49,250-50,015); Moreover, the weight after centrifugation was the same as that observed at the beginning of the experiment.

The water-swollen copolymer particles appeared to be unaffected by the enzyme used. It will be done. This result is consistent with the results regarding digestion and excretion.

Example 3 Antigenicity studies The purpose of this study is to determine the antigenic potential of copolymer particles. Therefore, Amounts of 2.0 g/day are administered for 5-20 days in the presence of water.

The following test was conducted after the start of the test and 4 days after the end.

1. Determine skin response after 20 minutes and 2 hours by puncture test with swollen material (immediate hypersensitivity).

λ Determine after 24 and 48 hours by patch test using swollen material (Cell-mediated hypersensitivity).

Tests were negative both immediately and delayed in all subjects. Therefore, Kopo Rimmer appears to be immunologically inactive.

Three of the 20 volunteer subjects during the study reported He complained of some heaviness in his stomach. However, there were no complaints of stomach pain or intestinal ulcers.

Finally, a slight laxative effect was observed in all spontaneous subjects.

Such an effect, if observed globally in a large number of subjects, may be due to dietary therapy. It should be noted that, on the contrary, they cannot be considered passive when it comes to weight loss. Living Physical hunger is eliminated and intestinal transit is facilitated.

Example 4 In vitro cell behavior research The behavior of immune competitive cells and phagocytic cells is analyzed on copolymer particles. some kind of grain Smaller diameter particles can probably cross the intestinal wall, so what happens to the particles? Therefore, it is useful to study the effects on immune function.

a) Cytotoxicity test Swollen particles with increased concentration (20,000 to 200,000) are used for allergic patients. A constant number of lymphomonocytes from individuals were added. RPM with 10% AB0 human serum Culture was performed in I medium. After 4 hours of culture, cells were treated with trypan blue. were mixed and the number of viable cells was determined within 10 minutes of contact.

The results are shown below as an average of 10 samples.

Raw concave dish Control 93% swollen particles 20.00095% Swelling particles 100.00088% Swelling particles 200.00092% b) Lymphocyte stimulation test Ten lymphomonocyte cultures were prepared, but the cells were from allergic patients. It was.

Culture was performed for 5 days in RPMI medium + 15% AB serum.

The cultures are: (phytohemagglutinin) 1 control loft of stimulated T-lymphocytes 1 lot using PHA midogin (lectin, vegetable meggin) 1 loft using Con-A (Concabalin A) stimulated 1978 ball Three types of lofts were cultured in parallel, with 5 swollen copolymer particles per 1 d of medium. Additional 0.000 sH-thymidine particles (1, Ouc/10' cell ), wash the cells and use a liquid scintillation counter (Venkman ) was used to measure isotope activity. The results are expressed in beats per minute. ) (bpm).

The results obtained are as follows.

-Fart + SE 1. Control 369 ± 171a, Control soil particles 375 ± 212, PHA 76.59 3 ± 7.2502a, PHA ten particles 74,781 ± 5 ．． 7203, Con-A 28.513 ± 1.78 03a, Con-A+ particles 29.557 ± 2.046 statistical The analysis (+ student test) is unified between 1 and 1a, 2 and 2a, 13 and 3a. No statistically significant difference.

Ultimately, at the concentrations used, copolymer particles inhibited lymphomonocyte cell division in vitro. Don't interfere.

C) Phagocytosis test Ficoll-1 sopaque with gradient end Isolated multinucleated cells from allergic patients were washed and the copo ratio was 115. 1 Five experiments were performed. The cell suspension was incubated at 37°C for 2 hours. Cell/particle binding Separation of the bodies was performed by sedimentation in a hypotonic aqueous medium.

Five hundred multinucleated cells were counted in each test and the presence of intracellular particles was determined.

No phagocytosis of particles was observed. Swollen particles are less likely to undergo phagocytosis Much larger than cells, however, a rosette shape was observed. That is, 4 to 8 A few multinucleated cells attached to the side of the particle, probably during an attempt at phagocytosis.

The same test was now performed using mononuclear cells isolated on glass plates. in this case Also, no phagocytosis was observed, but the same type of phagocytosis observed for multinucleated cells Some rosettes were present.

Phagocytes, multinucleated cells and mononuclear cells cannot eat vinyl/acrylic particles .

Example 5 poultice Igetagel® copolymer spheres marketed by Omarex A poultice with a size of 40 x 40 C1 and a thickness of 4 m was made by enclosing it in a non-woven envelope. However, the non-woven envelope may alternatively be covered with traditional gauze.

When these poultices are applied onto a wound, the absorbency of the poultice is comparable to that of traditional poultices. It performs significantly better than. In addition, they are used to treat wounds caused by external microorganisms. Acts significantly as a blocker against infection.

international search report EP 8900118 SA　26721 international search report

Claims (13)

[Claims] 1. Mainly the following basic groups: ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R1, R2, R3, R'1, R'2, R'3 are the same or different; It is often a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and Me is an alkali metal. and Z represents OH or CONH2 group] crosslinked hydrophilic alkaline copolymer A medical and paramedical product characterized in that it consists of: 2. The crosslinked hydrophilic copolymer has the following formula where Z=CONH2: ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ It is characterized by being a copolymer of acrylamide and sodium acrylate. 2. A product according to claim 1. 3. The following formula where the crosslinked hydrophilic copolymer is Z=OH: ▲The mathematical formula, chemical formula, table, etc. There is▼ It is characterized by being a copolymer of vinyl alcohol and sodium acrylate. A product according to claim 1. 4. The crosslinked hydrophilic copolymer has an average particle size in the dry state of 50 to 700 υm. 4. A product according to claim 1, 2 or 3, characterized in that it is in the form of a powder. 5. Cross-linked hydrophilic copolymers absorb 500 to 700 times their own volume of water in an aqueous environment. 4. A product as claimed in claim 2 or 3, characterized in that the product is gelatinized. 6. Diet for the treatment of obesity and morbid hunger or for weight loss characterized by being absorbed orally 2. A product according to claim 1 for dietary use. 7. 7. The product according to claim 6, characterized in that it has been processed into pills. 8. Used as a life-sustaining food characterized by containing nutrients and being absorbed orally A product according to claim 1. 9. Wrapped in cloth, diapers, napkins, pads, woven or non-woven bags A claim for use in health care characterized by being formed into a plaster or poultice. A product according to claim 1. 10. Claims characterized in that they contain active substances that have a healing or scar-forming effect The product according to Box 9. 11. Claims for medical or veterinary use characterized by the inclusion of active substances 1. Product according to 1. 12. Claims characterized in that they are processed for internal or external topical application. The product according to Box 11. 13. A maintenance or A product according to claim 1 for use in surgery as a filling material.