CN101453987A - Use of polymeric materials with other substances for improved performance - Google Patents
Use of polymeric materials with other substances for improved performance Download PDFInfo
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Abstract
Methods of enabling or improving the ability of a hydrogel to swell in the stomach of an animal and/or increasing the amount of time said hydrogel remains swollen in the stomach are described herein. In one embodiment, a polymer is administered in combination with one or more pH modifying agents which raise and maintain the pH of the micro environment of the polymer and/or the stomach in order inducing swelling in the polymer. The polymer can be a homopolymer, a copolymer, or a polymer blend or composite. In one embodiment, the polymer is a superabsorbent polymer (''SAP''). The polymers can also be administered with one or more active agents, such as appetite suppressants. The pH modifying agent and/or the active agent can be administered simultaneously with the polymer in the same dosage form, simultaneously with the polymer in separate dosage forms, or sequentially. The compositions are formulated for oral administration. The formulation can include drugs for delivery to the stomach, such as antibiotics, or the hydrogel can be used as filler, for example, for obesity control. The formulation an also be used to enhance gastric retention, for example, for controlled drug delivery. Methods of delivering a drug are also described herein, along with medicaments for carrying out the methods of the present invention.
Description
Related application
60/787,396 the benefit of priority that the application requires the U.S. Provisional Patent Application series number of submitting on March 28th, 2,006 60/786,615 and submitted on March 30th, 2006, both all are incorporated herein by reference in full at this.
Invention field
The present invention is to use the pH dependent polymers by causing suitable stomach pH value and by further uniting this polymer of use with causing other pharmacology and the surgical means that lose weight, causing the method field that loses weight and treat gastrointestinal disorder disease via machinery and physiology's mode.
Background of invention
The public keeps healthy and makes great efforts and the existing antiadipositas drug increased popularity of controlling obesity not as yet.This deficiency disorder active level plentiful owing to the food that is accompanied by the movement of population from the rural area to the city and that reduce in industrialized country becomes more and more popular.Fat being defined as roughly is the too much body fat that surpasses the required degree of keeping fit.
Fat relevant with the M ﹠ M that improves.The fat risk that the illeffects of health is comprised the cardiovascular disease and the raising of relevant hypertension, diabetes and hyperlipidemia.The millions of people is fat clinically, and considers fat illeffects to health, can benefit from treatment.In addition, although many people are not fat clinically, can improve its health and wellbeing by losing weight.
Fat pathogeny is multifactorial and comprises component and the gene and the psychological impact of control, fat stores mechanism, caloric intake and the consumption of feed behavior.Similarly, Fei Pang treatment is normally multifactorial.Unfortunately, generally speaking, fat stores mechanism and effect gene are not easy treatment.In addition, the control of feed behavior and psychological impact require long-term treatment.In addition, although the component of caloric intake and consumption is medicable, many obese individuals are resisted maybe can not participate in the activity that significantly improves its energy expenditure.Therefore, the control energy picked-up is the fat method of attractive treatment.
Various medicines and medicament categories are known to be fat-reducing and antiadipositas drug.These medicines are by the medicament that influences biological pathway, as 1) central nervous system's medicament of affect the nerves mediator or neural ion path; 2) leptin (leptin)/insulin/central nervous system's path medicament; 3) gastrointestinal-nervous pathway medicament; 4) can improve the medicament (" selectivity " β-3 stimulants/agonist, Uncoupling Proteins homologue and thryoid receptor agonist) of rest metabolic rate; With 5) other more various medicament formation.But these inhibitor do not produce usually as the true satiety that is come by " expiring " stomach band and/or they and cause unacceptable side effect, as anxiety and superfunction, and may have disadvantageous side effect.
Amphetamine (dextro-amphetamine) has been used as fat-reducing and antiadipositas drug, but may cause unacceptable tachycardia and hypertension.They also have high abuse potential.Other sympathomimetic nerve adrenergic agent comprises that Duromine, benzphetamine, phendimetrazine, Mazindol and diethylpropion may have disadvantageous cardiovascular side effects, and their treatment application only is short-term (12 week).In 2000, the appetite suppressant phenylpropanolamine was removed from American market owing to unacceptable risk of stroke (especially in the adult female).Other appetrol also have disadvantageous side effect as orlistat and sibutramine.For example, the use of orlistat causes usually and comprises flatulence, oiliness feces, the just rough sledding of urgency or fecal incontinence and stomachache, is not particularly observing among the patient of the low fat diet of recommending.In addition, recommend to replenish every day multivitamin with the absorption that prevents contingent in theory fatsoluble vitamin (A, D, E and K) when the life-time service impaired may.The use of sibutramine may improve blood pressure and heart rate, and its use is incompatible in the patient of not controlled hypertension, CHD, arrhythmia, congestive heart failure or apoplexy.
Be as known in the art and lose weight with Bariatric and realization and to link together as the satiety of appetite inhibiting means.For example, people's such as Acharya U.S. Patent No. 5,336,486 has been described by fill the false satiety that stomach causes with a large amount of digestible Plant fiber.But, to take in a large amount of fiber requirement patients and discharge a large amount of fibers, this may cause gastrointestinal upset.Some can not bear so high fibre weight for other reasons.In order to alleviate the discomfort that is caused by the full abdomen that makes the Plant fiber be higher than normal value the time of staying, the easy digestion product that has a lower calorific value by interpolation improves the diet prescription based on the Plant fiber.U.S. Patent No. 5,063,073 referring to Kratochvil; People's such as people's such as Christensen 5,654,028 and Grace 6,426,077.People's such as Wounderlich United States Patent(USP) Nos. 5,405,616 and 6,103,269 have described the material that is made of gelatin or collagen hydrolysate, one or more active agents and one or more excipient (being plasticizer, odorant etc.).This material with solution or form of suspension manufacturing and lyophilizing subsequently to obtain solid material.This solid material can be with powder, tablet or capsule form administration.When exsiccant polymeric material contacted with the aqueous medium of stomach, it is swelling in a few minutes at first, and dissolving subsequently produces the solution that does not disturb the gastrointestinal tract emptying.
The lower calories prod that is used for controlling body weight can use the collagen biopolymer, obtains as soluble collagen, gelatin or collagen hydrolysate.Referring to United States Patent(USP) Nos. 5,100,688,5,211,976,5,219,599,5,665,234,5,665,419.As EYI-Essentially Yours Industries, " the Dietary Supplement-CALORAD that Inc.-USA produces
" and so on commodity be used to lose weight control and as the muscular irritation agent, and the auxiliary agent used of osteoporosis auxiliary agent and arthritis treatment.
But, these medicines and material none for the user safe enough gratifying obesity control means are provided or cause the means that lose weight.
Absorbing material to water and aqueous medium (fluid that comprises human secretory) is known in the document.These materials normally polymer-matrix and with powder, granule, microgranule or fibers form manufacturing.When contacting with aqueous medium, these polymeric materials are swelling by liquid phase being sucked its structure, but is not dissolving." hydrogel " is the polymeric material with suction and swelling ability.If water absorption rate is greater than 20 gram water/gram dry polymers, this material is known as " super absorbent polymer " (SAP).These materials swelling under one's belt can cause satiety (promptly full stomach).Be as known in the art and be used for the treatment of obesity and/or caused and lose weight as the satiety of appetite inhibiting means.
Polymeric hydrogel also has been used for controlled drug delivery, especially for slow release and/or delayed release dosage system.In medicinal usage, medicine is dispersed in the polymeric material usually.Drug release rate depends on the speed that medicine spreads and/or the degradation rate of polymeric material from hydrogel.One of oral common use two class hydrogels of medicine: a) discharge those and b of medicine under one's belt) in small intestinal or other position such as oral cavity, duodenum etc., discharge those of medicine.The purposes that hydrogel utilizes " full abdomen " principle to be used for the active agent controlled release has been described in people's such as Johnson U.S. Patent No. 3,574,820; 4,264,493 of Battista; People's such as Caldwell 4,758,436; 5,614,223 of Sipos; 6,319,510 of Yates; People's such as Flashner-Barak 6,476,006 and Zuckerman 6,485,710 in.
The stomach secretion that generates gastric juices, it is the aqueous medium that contains water, hydrochloric acid, pepsin and mucus (polysaccharide biogel).This medium has the pH value of 1-3 and contains the pepsin proteolytic enzyme.Compare with stomach, intestinal secretion goes out the more complicated aqueous medium of chemical composition.Its pH value with 5-9 is feature and is demonstrating the biological degradability enzymatic activity aspect protein and the polysaccharide.Estimate the hydrogel play a role under one's belt must (1) in acidic aqueous media swelling and keep its volume to reach being enough to causing treatment and be correlated with time of effectiveness; (2) once realizing the removal easily of its function, to avoid intestinal or gastropore to block and to avoid generation that toxic byproduct is arranged.
Unfortunately, the many hydrogels that can be used for therapeutic use (comprise and losing weight and Bariatric) not swelling or difference ground swelling in the acid ph value of stomach.People such as Park confirm that the swelling ratio of poly-(acrylamide-be total to-acrylic acid) depends on the pH value of medium.Under about 5 pH value, hydrogel shows maximum swelling.By between 1.2 to 7.5, changing PH values, poly-(acrylamide-altogether-acrylic acid) shows repeatedly swelling and contraction, and (people such as Park, J Biomater Sci Polym Ed. at a good pace take place in big approximate number minute in the change of swelling ratio, 11 (12), 1371-80 (2000)).People such as Peppas have described the copolymer of methacrylic acid (MAA) and 2-methacryloxyethyl glucoside (MEG), have pH dependency swelling, swelling wherein take place and the transformation between the state of caving under pH5.Be higher than under 5 the pH value, the swelling ratio of hydrogel improves people such as (, J.Biomater.Sci.Polymer Edn, the 13rd volume, No.11,1271-1281 page or leaf (2002)) Peppas.
People's such as Ron US5,876,741 have described the hydroxypropyl cellulose crosslinked with adipic acid (HPC) hydrogel, its show in pH＜5.0 time have minimum response and at pH have the swelling curve of remarkable response 5.0 time.The crosslinked HPC hydrogel of this and adipic acid shows the result of near ideal, and wherein the water absorption rate under pH＜5.0 is 0, time medium swelling in 5＜pH＜7, and at pH〉surpass 20 times of swellings 7 time.
Need be under the low acidity of stomach the swelling of initiated polymerization hydrogel to treat the method for fat and other stomach deficiency disorder.
Therefore the purpose of this invention is to provide employing machinery and physiology mode causes satiety and reduces appetite to treat method fat and other stomach deficiency disorder.
Summary of the invention
On the one hand, the present invention relates to realize or improve hydrogel in the animal stomach the swelling ability and/or increase the method that described hydrogel keeps swollen time quantum under one's belt, comprise to animal giving with one or more raisings and keeping the water-swellable polymer of material associating of the microenvironment pH value of polymer and/or stomach.In other embodiments, polymer is a super absorbent polymer.In other embodiments, polymer is selected from homopolymer, copolymer, polymer blend, cross linked polymer, polymer composites and combination thereof.In other embodiments, polymer is a polymer composites.
In other embodiments, one or more materials that change pH value are selected from buffer agent, H
2Blocker, proton pump inhibitor, antacid, protein, nutrition bland (nutritionalshakes) and combination thereof.In other embodiments, buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.In other embodiments, the H2 blocker is selected from Altramet, ranitidine, famotidine, nizatidine and combination thereof.In other embodiments, proton pump inhibitor is selected from omeprazole, lansoprazole, esomeprazole, pantoprazole, Lei Beila frustrates and make up.In other embodiments, antacid is selected from aluminium hydroxide, magnesium hydroxide, aluminium carbonate, calcium carbonate and brucite.
In other embodiments, polymer further comprises one or more pharmaceutically acceptable excipient, is selected from plasticizer, diluent, binding agent, lubricant, coloring agent, stabilizing agent, surface-active agents, spice, antiseptic, antioxidant, buffer agent and combination thereof.In other embodiments, this buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
In other embodiments, polymer is with one or more therapeutic active agents, diagnostic reagent or the administration of prophylactic activity reagent.In other embodiments, this reagent is selected from analgesic, the antibiotic medicine, antipyretic, antidepressants, antiepileptic medicine (altiepileptics), hydryllin, antimigraine, anti-muscarine medicine, antianxiety drugs (anxioltyics), tranquilizer, sleeping pill, psychosis, bronchodilator, antasthmatic, cardiovascular drug, corticosteroids, dopaminergic, electrolytes, gastrointestinal drug, muscle relaxant, nutrient, vitamin, parasympathomimetic agent, stimulant, anorexigenic, appetite suppressant, antiadipositas drug, anti-narcolepsy medicine (anti-narcoleptics) and combination thereof.In other embodiments, this reagent is appetite suppressant or antiadipositas drug.In other embodiments, appetite suppressant or antiadipositas drug are selected from Sibutramine hydrochloride, orlistat, Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.
In other embodiments, prepare described polymer and be used for oral administration.In other embodiments, preparaton is selected from tablet, capsule, syrup, solution, suspension, powder, stick (bars) and bland (shakes).
In other embodiments, the material of the microenvironment pH value of raising polymer and/or stomach and polymer are with same dosage form administration simultaneously.In other embodiments, the material of the microenvironment pH value of raising polymer and/or stomach and polymer are with different dosage form administration simultaneously.In other embodiments, improve material administration before or after polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 24 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 2 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 6 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.
In other embodiments, method of the present invention further comprises the material that gives to cause hydrogel degraded, dispersion and/or contraction after hydrogel stays for some time under one's belt.In other embodiments, the administration after polymeric drug delivery of this material.In other embodiments, this material is used to reduce the microenvironment pH value of polymer and/or stomach.In other embodiments, this material is an organic acid.In other embodiments, this material is an acidic beverages, as orange juice or coca cola.In other embodiments, this material is a protein.In other embodiments, this protein is enzyme.In other embodiments, this enzyme is selected from pepsin, pancreatin and combination thereof.
In other embodiments, the surgical operation of polymer and material and obesity is co-administered.In other embodiments, the surgical operation of treatment of obesity is selected from gastric banding, gastric bypass, built-in gastric qi ball, the electricity irritation of implantable gastric stimulator stomach function regulating.
In other embodiments, the water-swellable preparaton is the optional bland form that comprises vitamin, mineral or nutriment, and it effectively improves stomach pH value with the swelling, the complementary diets nutrition that strengthen polymer or cause satiety and lose weight.
In other embodiments, animal is primates, cattle, sheep, horse, pig, birds, rodent, felid or Canis animals.In other embodiments, animal is human.
On the other hand, the present invention relates to method, comprise to animal comprising the water-swellable polymer of medicine and the material of the microenvironment pH value of one or more raising polymer and/or animal stomach to the defeated drug delivery of animal.In other embodiments, medicine discharges from polymer in the slow release mode.In other embodiments, medicine is selected from therapeutic active agents, diagnostic reagent and prophylactic activity reagent.In other embodiments, this reagent is selected from analgesic, antibiotic medicine, antipyretic, antidepressants, antiepileptic medicine, hydryllin, antimigraine, anti-muscarine medicine, antianxiety drugs, tranquilizer, sleeping pill, psychosis, bronchodilator, antasthmatic, cardiovascular drug, corticosteroids, dopaminergic, electrolytes, gastrointestinal drug, muscle relaxant, nutrient, vitamin, parasympathomimetic agent, stimulant, anorexigenic, appetite suppressant, antiadipositas drug, anti-narcolepsy medicine and combination thereof.In other embodiments, this reagent is appetite suppressant or antiadipositas drug.In other embodiments, appetite suppressant or antiadipositas drug are selected from Sibutramine hydrochloride, orlistat, Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.
In other embodiments, polymer is a super absorbent polymer.In other embodiments, polymer is selected from homopolymer, copolymer, polymer blend, cross linked polymer, polymer composites and combination thereof.In other embodiments, polymer is a polymer composites.
In other embodiments, one or more materials that change pH value are selected from buffer agent, H
2Blocker, proton pump inhibitor, antacid, protein, nutrition bland and combination thereof.In other embodiments, buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.In other embodiments, H
2Blocker is selected from Altramet, ranitidine, famotidine, nizatidine and combination thereof.In other embodiments, proton pump inhibitor is selected from omeprazole, lansoprazole, esomeprazole, pantoprazole, Lei Beila frustrates and make up.In other embodiments, antacid is selected from aluminium hydroxide, magnesium hydroxide, aluminium carbonate, calcium carbonate and brucite.
In other embodiments, polymer further comprises one or more pharmaceutically acceptable excipient, is selected from plasticizer, diluent, binding agent, lubricant, coloring agent, stabilizing agent, surface-active agents, spice, antiseptic, antioxidant, buffer agent and combination thereof.In other embodiments, buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
In other embodiments, prepare described polymer and be used for oral administration.In other embodiments, this preparaton is selected from tablet, capsule, syrup, solution, suspension, powder, stick and bland.
In other embodiments, the material of the microenvironment pH value of raising polymer and/or stomach and polymer are with same dosage form administration simultaneously.In other embodiments, the material of the microenvironment pH value of raising polymer and/or stomach and polymer are with different dosage form administration simultaneously.In other embodiments, improve material administration before or after polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 24 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 2 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 6 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.
In other embodiments, method of the present invention further comprises the material that gives to cause hydrogel degraded, dispersion and/or contraction after hydrogel stays for some time under one's belt.In other embodiments, the administration after polymeric drug delivery of this material.In other embodiments, this material is used to reduce the microenvironment pH value of polymer and/or stomach.In other embodiments, this material is an organic acid.In other embodiments, this material is an acidic beverages, as orange juice or coca cola.In other embodiments, this material is a protein.In other embodiments, this protein is enzyme.In other embodiments, this enzyme is selected from pepsin, pancreatin and combination thereof.
In other embodiments, the surgical operation of polymer and material and obesity is co-administered.In other embodiments, the surgical operation of treatment of obesity is selected from gastric banding, gastric bypass, built-in gastric qi ball, the electricity irritation of implantable gastric stimulator stomach function regulating.
In other embodiments, the water-swellable preparaton is the optional bland form that comprises vitamin, mineral or nutriment, and it effectively improves stomach pH value with the swelling, the complementary diets nutrition that strengthen polymer or cause satiety and lose weight.
In other embodiments, animal is primates, cattle, sheep, horse, pig, birds, rodent, felid or Canis animals.In other embodiments, animal is human.
In other embodiments, method of the present invention is used for the treatment of obesity, cause and lose weight and/or improve gastric retention.
On the other hand, the present invention relates to realize or improve hydrogel in the animal stomach the swelling ability and/or increase the medicament that described hydrogel keeps swollen time quantum under one's belt, it comprises with one or more raisings and keeps the water-swellable polymer of material associating of the microenvironment pH value of polymer and/or stomach.In other embodiments, polymer is a super absorbent polymer.In other embodiments, polymer is selected from homopolymer, copolymer, polymer blend, polymer composites and combination thereof.In other embodiments, polymer is a polymer composites.
In other embodiments, one or more materials that change pH value are selected from buffer agent, H
2Blocker, proton pump inhibitor, antacid, protein, nutrition bland and combination thereof.In other embodiments, buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.In other embodiments, the H2 blocker is selected from Altramet, ranitidine, famotidine, nizatidine and combination thereof.In other embodiments, proton pump inhibitor is selected from omeprazole, lansoprazole, esomeprazole, pantoprazole, Lei Beila frustrates and make up.In other embodiments, antacid is selected from aluminium hydroxide, magnesium hydroxide, aluminium carbonate, calcium carbonate and brucite.
In other embodiments, this medicament further comprises one or more pharmaceutically acceptable excipient, is selected from plasticizer, diluent, binding agent, lubricant, coloring agent, stabilizing agent, surface-active agents, spice, antiseptic, antioxidant, buffer agent and combination thereof.In other embodiments, buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
In other embodiments, this medicament further comprises one or more therapeutic active agents, diagnostic reagent or prophylactic activity reagent.In other embodiments, this reagent is selected from analgesic, antibiotic medicine, antipyretic, antidepressants, antiepileptic medicine, hydryllin, antimigraine, anti-muscarine medicine, antianxiety drugs, tranquilizer, sleeping pill, psychosis, bronchodilator, antasthmatic, cardiovascular drug, corticosteroids, dopaminergic, electrolytes, gastrointestinal drug, muscle relaxant, nutrient, vitamin, parasympathomimetic agent, stimulant, anorexigenic, appetite suppressant, antiadipositas drug, anti-narcolepsy medicine and combination thereof.In other embodiments, this reagent is appetite suppressant or antiadipositas drug.In other embodiments, appetite suppressant or antiadipositas drug are selected from Sibutramine hydrochloride, orlistat, Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.
In other embodiments, prepare described medicament and be used for oral administration.In other embodiments, this preparaton is selected from tablet, capsule, syrup, solution, suspension, powder, stick and bland.
In other embodiments, the material and the polymer that improve the microenvironment pH value of polymer and/or stomach are same dosage form.In other embodiments, the material and the polymer that improve the microenvironment pH value of polymer and/or stomach are different dosage form.
In other embodiments, medicament of the present invention further is included in the material that causes depolymerization, dispersion and/or contraction after polymer stays for some time under one's belt.In other embodiments, this material is used to reduce the microenvironment pH value of polymer and/or stomach.In other embodiments, this material is an organic acid.In other embodiments, this material is an acidic beverages, as orange juice or coca cola.In other embodiments, this material is a protein.
In other embodiments, this medicament is the optional bland form that comprises vitamin, mineral or nutriment, and it effectively improves stomach pH value with the swelling, the complementary diets nutrition that strengthen polymer or cause satiety and lose weight.
On the other hand, the present invention relates to fail the medicament that drug delivery is used, comprise the water-swellable polymer that contains medicine and improve the material of the microenvironment pH value of polymer and/or animal stomach with one or more to animal.In other embodiments, this medicine discharges from polymer in the slow release mode.In other embodiments, this medicine is selected from therapeutic active agents, diagnostic reagent and prophylactic activity reagent.In other embodiments, this reagent is selected from analgesic, antibiotic medicine, antipyretic, antidepressants, antiepileptic medicine, hydryllin, antimigraine, anti-muscarine medicine, antianxiety drugs, tranquilizer, sleeping pill, psychosis, bronchodilator, antasthmatic, cardiovascular drug, corticosteroids, dopaminergic, electrolytes, gastrointestinal drug, muscle relaxant, nutrient, vitamin, parasympathomimetic agent, stimulant, anorexigenic, appetite suppressant, antiadipositas drug, anti-narcolepsy medicine and combination thereof.In other embodiments, this reagent is appetite suppressant or antiadipositas drug.In other embodiments, appetite suppressant or antiadipositas drug are selected from Sibutramine hydrochloride, orlistat, Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.
In other embodiments, polymer is a super absorbent polymer.In other embodiments, polymer is selected from homopolymer, copolymer, polymer blend, cross linked polymer, polymer composites and combination thereof.In other embodiments, polymer is a polymer composites.
In other embodiments, one or more materials that change pH value are selected from buffer agent, H2 blocker, proton pump inhibitor, antacid, protein, nutrition bland and combination thereof.In other embodiments, buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.In other embodiments, the H2 blocker is selected from Altramet, ranitidine, famotidine, nizatidine and combination thereof.In other embodiments, proton pump inhibitor is selected from omeprazole, lansoprazole, esomeprazole, pantoprazole, Lei Beila frustrates and make up.In other embodiments, antacid is selected from aluminium hydroxide, magnesium hydroxide, aluminium carbonate, calcium carbonate and brucite.
In other embodiments, polymer further comprises one or more pharmaceutically acceptable excipient, is selected from plasticizer, diluent, binding agent, lubricant, coloring agent, stabilizing agent, surface-active agents, spice, antiseptic, antioxidant, buffer agent and combination thereof.In other embodiments, buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
In other embodiments, prepare described polymer and be used for oral administration.In other embodiments, this preparaton is selected from tablet, capsule, syrup, solution, suspension, powder, stick and bland.
In other embodiments, the material of the microenvironment pH value of raising polymer and/or stomach and polymer are with same dosage form administration simultaneously.In other embodiments, the material of the microenvironment pH value of raising polymer and/or stomach and polymer are with different dosage form administration simultaneously.In other embodiments, improve material administration before or after polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 24 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 2 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.In other embodiments, improve material administration in 6 hours of polymeric drug delivery of the microenvironment pH value of polymer and/or stomach.
In other embodiments, medicament of the present invention further is included in the material that causes the hydrogel degraded after hydrogel stays for some time under one's belt, disperses and/or shrink.In other embodiments, the administration after polymeric drug delivery of this material.In other embodiments, this material is used to reduce the microenvironment pH value of polymer and/or stomach.In other embodiments, this material is an organic acid.In other embodiments, this material is an acidic beverages, as orange juice or coca cola.In other embodiments, this material is a protein.In other embodiments, this protein is enzyme.In other embodiments, this enzyme is selected from pepsin, pancreatin and combination thereof.
In other embodiments, the surgical operation of this medicament and obesity is co-administered.In other embodiments, the surgical operation of treatment of obesity is selected from gastric banding, gastric bypass, built-in gastric qi ball, the electricity irritation of implantable gastric stimulator stomach function regulating.
In other embodiments, the water-swellable preparaton is the optional bland form that comprises vitamin, mineral or nutriment, and it effectively improves stomach pH value with the swelling, the complementary diets nutrition that strengthen polymer or cause satiety and lose weight.
In other embodiments, animal is primates, cattle, sheep, horse, pig, birds, rodent, felid or Canis animals.In other embodiments, animal is human.
According to following description and claim, these embodiments of the present invention, other embodiment and their key element and feature are apparent.
Detailed Description Of The Invention
I. definition
Term " polymer " composite used herein " be meant the macromolecular material that constitutes by two or more polymer chains, wherein polymer chain is via noncovalent interaction, as interactions such as Van der Waals force, hydrogen bonding, ionic interactions.Composite has the three-dimensional network type macromolecular conformation by multiple key type stabilisation.
Term used herein " polymer blend " is meant the uniform mixture of the macroscopic view of two or more different polymer.
II. hydrogel and realization and/or improve the method for swelling behavior
This paper has described by containing polymer and one or more raisings and keeping polymer and/or the microenvironment pH value of stomach and increase the compositions that polymer keeps the pH value regulator of swollen time under one's belt and realize and/or improve hydrogel swollen method in animal or human's class stomach.
A. polymer
Polymer can be homopolymer, copolymer, cross linked polymer, polymer blend or polymer composites.In one embodiment, polymer is a super absorbent polymer.The suitable polymers that can form hydrogel includes but not limited to synthetic or natural polymer.The example of synthetic polymer comprises polyacrylic acid and polymethacrylic acid polymer, cellulose derivative, as hydroxypropyl cellulose, and polyethylene glycol polymer, copolymer and block copolymer and other water-swellable, biocompatible polymer.The example of natural polymer comprises collagen, hyaluronic acid, gelatin, albumin, polysaccharide and derivant thereof.Natural polymer also can be an isolating type from each plant material such as Herba Plantaginis.
Structurally, the water absorbent polymer material is three-dimensional macromolecular conformation.They are by the several method manufacturing: a) by monomer synthetic (cross-linked polymeric); B) by polymer and reagent and additive in polymerization synthetic (grafting and cross-linked polymeric); C) by polymer and non-polymeric auxiliary agent synthetic (cross linked polymer); D) synthesize (by reactive polymer-polymer mutual coupling come crosslinked) by polymer synthetic (cross linked polymer of no auxiliary agent) with e) by polymer with the energy.Generation that used raw material and technology are the hydrogel key property in synthetic and the principal element in the range of application thereof.
Exist dose known amounts be used for obtain to have three-dimensional polymer structure and have the method for the high-purity absorbent material of aqueous medium of potential use at medicine and/or medical field: a) chemical method: the mutual complexation of ion and/or coordination (is the U.S. Patent No. 4 of Widra, 570,629 and people's such as Band U.S. Patent No. 5,153,174); With oligomer with the reactive group that contains two keys or ring or reactive polymer crosslinked (being people's such as people's such as Franzblau U.S. Patent No. 5,489,261 and Doillon U.S. Patent No. 5,863,984); Crosslinked under radiation (be people's such as Kuamz U.S. Patent No. RE33,997; The U.S. Patent No. 4,264,155 of Miyata; U.S. Patent No. 5,948,429 with people such as Bell); And b) physical method: with microwave crosslinked (being people's such as Reichman United States Patent(USP) Nos. 5,859,077 and 6,168,762); Lyophilizing (be people such as people's such as Williams United States Patent(USP) Nos. 5,676,967 and McGregor 5,869,080); With the dehydrogenation heat cross-linking (be people's such as Berg U.S. Patent No. 4,837,285; People's such as Akhtar U.S. Patent No. 4,950,485; U.S. Patent No. 4,971,954 with people such as Brodsky).
The dehydrogenation heat cross-linking is the same with other physical method that is used for obtaining three dimensional structure have been eliminated and may change the poisonous effect risk that (novel covalent bond, ionic bond or coordinate bond wherein occurring) produces by the reaction secondary product or in the energy state of the contingent product of activation of some chemical methods.In addition, compare with lyophilizing or via microwave is crosslinked, the dehydrogenation heat cross-linking provides more probabilities (that is, Scotchford C.A., the Cascone.G.D. that regulates the architectural characteristic of gained three-dimensional network, OwnesS., Gusti P., ＂ Osteoblast responses of collagen-PVA bioartificial polymers invitro:the effects of cross-linking method and collagen content ＂, Biomaterials 19,1-11,1998; Giunchedi P., Genta I., Conti B., MuzzarelliR.A.A., Conti B., Biomaterials 19,157-161,1998).But, do not have high absorbent capacity based on the hydrogel of the collagen biopolymer that obtains by the dehydrogenation heat cross-linking.
B.pH value regulator
Polymeric material can with one or more pH value regulator co-administereds to improve and to keep the microenvironment pH value of polymer and/or stomach.Suitable pH value regulator comprises buffer agent, proton pump inhibitor, H2 blocker and antacid.The example of these pH value regulators is described below.Compositions can be served as the stomach packing material, its swelling and produce satiety when hydration.The pH value regulator can with polymer with same dosage form administration simultaneously, with polymer administration simultaneously in the dosage form of separating, or administration in succession.If the administration in succession of pH value regulator and polymer composition, then the pH value regulator preferably in 24 hours of polymer composition administration, more preferably in 12 hours, most preferably administration in 6 hours.
The i buffer agent
Suitable pH buffer agent includes but not limited to ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
The ii proton pump inhibitor
Suitable proton pump inhibitor includes but not limited to omeprazole
Omeprazole with the bicarbonate associating
Lansoprazole
Esomeprazole
Pantoprazole
Frustrate with Lei Beila
Iii H
2Blocker
Appropriate H
2Blocker includes but not limited to Altramet
Ranitidine
Famotidine
Famotidine with calcium carbonate and magnesium hydroxide associating
Complete) and nizatidine
The iv antacid
Suitable OTC (over-the-counter) antacid includes but not limited to aluminium hydroxide
Magnesium hydroxide (Milk of
Aluminium hydroxide with the magnesium hydroxide associating
Basaljel
Calcium carbonate
Rich calcareous
And brucite
C. active agent
Compositions also can be used for controlled defeated the passing of one or more therapeutic active agents, diagnostic reagent or preventive.The rate of release of active agent depends on the speed that active agent spreads and the degradation rate of polymer composites from hydrogel.
Exemplary agents comprises analgesic, anti-inflammatory agent, anthelmintic, anti-arrhythmic, antibacterial, antiviral agent, antihypertensive, anticoagulant, antidepressants, antidiabetic drug, antuepileptic, antifungal, antigout drug, antimalarial drug, antimigraine, anti-muscarine medicine, antineoplastic agent, erection disturbance improves medicine, immunosuppressant, protozoacide, the antithyroidin medicine, antianxiety drugs, tranquilizer, sleeping pill, Antipsychotic drug,-blocker, cardiac inotropic drug, corticosteroids, diuretic, antiparkinsonism drug, gastrointestinal agent, histamine H 1 and bisfentidine, keratolytic, fat regulation medicine, anti-anginal drug, nutrient, opioid analgesics, sex hormones, analeptic, muscle relaxant, ALENDRONATE FOSAMAX, antiadipositas drug, cognitive enhancer, resinferatoxin, nutritional oil, anti-benign prostatauxe medicine, essential fatty acid, non-essential fatty acid, vitamin, mineral, appetite suppressant and composition thereof.
In one embodiment, polymer composition and appetite suppressant administering drug combinations.Appetite suppressant can administration before or after the polymer composition administration.Perhaps, appetite suppressant can with polymer composition administration simultaneously.Suitable appetite suppressant includes but not limited to Meridia (can available from the Sibutramine hydrochloride of Abbott Laboratories), Xenical (can available from the orlistat of Roche USA), Acomplia (Rimonabant, by the Sanofi-Aventis exploitation and wait for the FDA approval), Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.Polymer composition also can with the surgical intervention of treatment of obesity, co-administered as gastric banding, gastric bypass, built-in gastric qi ball, implantable gastric stimulator (waiting for the U.S. approval) stomach function regulating electricity irritation (waiting for the U.S. approval).
D. other excipient
Polymer composites as herein described can be prepared controlled release to treat various gastrointestinal disorder diseases and one or more active agents are provided with one or more pharmaceutically acceptable excipient.Suitable excipient comprises pH value regulator, plasticizer, coloring agent, spice, antiseptic, antioxidant, surface-active agents, dispersant, fluidizer, diluent, binding agent and combination thereof.
E nutrition bland
Bland comprises any beverage that contains food additive.Food additive includes but not limited to flavouring agent, vitamin, mineral and buffer agent.In one embodiment, polymer composition is with bland form or the bland administering drug combinations taken with the patient.The bland that contains vitamin, mineral, optional nutriment can play the effect of the nutrient that the patient is provided can not absorbs because the dining amount reduces.Bland can contain the protein of one or more and polymer composition co-administered.As known in the art is that protein can improve and keep the pH value of stomach.Bland can contain and improves stomach pH value so that polymers swell and bring into play the buffer agent of therapeutic effect.This class buffer agent can include but not limited to ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.Bland can contain any combination of vitamin, mineral and buffer agent.The known initiation satiety of many blands, thus lose weight (Slim for example
Polymer can with promoting the bland coupling that has advantageous effect aspect the satiety.Polymer can with commercially available bland coupling to improve stomach pH value and/or essential nutrients that the patient lacks because of the dining amount reduces and/or the satiety effect that produces raising be provided.Commercially available bland includes but not limited to Slim
Protein Meal Chocolate Shake (protein meals chocolate bland), Optimum Nutrition Complete Protein Diet MealShake Mix (best nutritional complete protein go on a diet meals bland mixture), Walker DietLow Carb Shake (pedestrian go on a diet low-carbon (LC) bland), Walker
FiberCombinations (fiber combinations), Diet Lean Low Carb Shakes (the weight reducing low-carbon (LC) bland of going on a diet),
Diet Lean-Low Carb Dieter ' s Shake (weight reducing of going on a diet-low-carbon (LC) diet keeper's bland), DIET SHAKE VANILLA
NUTRITIONALS (nutriment), OxeSlim Diet Shake (bland of going on a diet) 2Go, Protein Drink Mix by
The protein beverage mixture), Formula 1 Nutritional Shake Mix by
Prescription 1 nutrition bland mixture), Basic Organics Pat ' s Diet Shake (basic organic yellow oil clot go on a diet bland), UNIVERSA L
Specialized Protein for Dieting (special type go on a diet protein), Meal Replacement Protein Shake by SportPharma (meals of SportPharma substitute the protein bland),
Whey ProteinShake
The whey protein bland),
For Women NutritionShake (the woman nutrition bland of eating for right to life), Chocolate (chocolate),
Soy Protein Powder Natural (crude soya bean egg albumen powder),
RtdShake (bland),
NITRO-Tech RTDs,
Slim Shake (weight reducing bland),
Soy Protein Shake (soybean protein bland),
Sport (sports drink),
Lite (light beverage), Protein Diet by Optimum (optimization protein food), Power Shake (powder mixes beverage),
Meal Replacement Protein Shake (meals substitute the protein bland), NRG Protein Booster (protein fortifier), Nature ' s
KetoslimShake (bland),
Shakes (bland),
All OnePowder (one powder), Total Soy French Vanilla (full Semen sojae atricolor french vanilla), BalanceTotal Balance Drink Mix (balanced complete balanced beverage mix), Pro V60 Straw, Slim﹠amp; Trim Vanilla Cream (slender and well-balanced Rhizoma et radix valerianae butter), Scitec Nutrition Protein (nutrient protein) Delite,
Meal Replacement (dietary substitute),
High Protein Complete Balanced Nutrition Drink (the complete balanced nutritious beverage of high protein).
III. medication
The common oral administration of polymer composition.Suitable peroral dosage form comprises medicament, capsule, capsule sheet, powder, syrup, solution, suspension and bland.In one embodiment, polymer composition is suppressed formation tablet with optional with one or more pH value regulators and/or one or more active agents with one or more excipient.The suitable excipient that is used to prepare tablet comprises binding agent, antiseptic, antioxidant, fluidizer, spice, coloring agent and combination thereof.
In one embodiment, polymeric encapsulate is in hard or Perle.The capsule inserts contains polymer and chooses any one kind of them or multiple pH value regulator and/or active agent.Inserts also can contain one or more excipient.Suitable excipient includes but not limited to plasticizer, crystallization inhibitor, wetting agent, extender filler (bulk filling agent), solubilizing agent, bioavailability reinforcing agent, solvent and combination thereof.In case hydrogel stops appropriate time (thereby appetite-suppressing and/or discharge one or more active agents) under one's belt, can make polymer composition degraded, dispersion or ablation to alleviate satiety and/or to avoid uncomfortable and/or the infringement patient.In one embodiment, improve the material of microenvironment acidity of polymer and/or stomach so that polymer shrinks (by reducing pH value).Suitable material includes but not limited to organic acid, as citric acid and phosphonate.Comprise proteinic polymer for part, enzyme such as pepsin or pancreatin are suitable materials.
Unless indicate separately, all technology used herein and scientific terminology all have the identical meanings of technical staff's common sense of disclosure field that the present invention belongs to.The publication that this paper enumerates and their cited materials are incorporated herein by reference especially.One skilled in the art will realize that or can only use normal experiment to conclude many counterparts of specific embodiments of the present invention as herein described.This class counterpart is intended being included in the following claim.
IV. body build-in test
Under different experimental conditions, give the laboratory rat polymeric material of the present invention, PMSF-1 (referring to the embodiment 1 in the embodiment part) by oral tube feed.PMSF-1 is according to U.S. Patent No. 6,833,488 and PCT publication application No.WO2005/084724A1 in the program preparation that provides, both all are incorporated herein by reference in full at this.Animal is sacrificed, excise their stomach and analyze gastric content.Do not notice acute poisoning or behavior change in the animal behind oral tube feed PMSF-1.After rat is sacrificed, in rat stomach, do not observe macroscopic (gross) histopathology.In rat stomach, observe PMSF-1 element (device),, notice that the time of staying increases for the animal of premedication H2 blocker or the animal of after this element (device) administration, taking food.
The main purpose of this research is the PMSF-1 time of staying of understanding in the rat stomach of oral tube feed PMSF-1 under three kinds of different experimental conditions, 1) when animal is not taken food behind picked-up PMSF-1; 2) when before oral tube feed polymer, giving the H2 blocker of animal raising stomach pH value; With 3) when allowing animal behind oral tube feed PMSF-1 polymer, to take food.Use the range estimation and the quantized combination of gastric content to reach a conclusion.Compare with the animal that does not receive the H2 blocker, the animal of premedication H2 blocker put in observing time obviously has more substantial PMSF-1 in its stomach.For example, behind oral tube feed PMSF-1 90 minutes, from the rat stomach of premedication H2 blocker, reclaim 27% of original PMSF-1, in contrast to this, in the time of 90 minutes, never receive in the rat of H2 blocker and do not reclaim PMSF-1.In addition, the food of verified raising stomach pH value also causes PMSF-1 to keep the swelling longer time, and this is consistent with the observed result of use H2 blocker.
The secondary objective of this research is whether the oral tube feed of measuring the PMSF-1 material produces any macroscopic toxicology or tangible GI pathology.In animal, do not observe emergency toxicology.In addition, defecate and denseness are normal, show normal GI function.The histopathological examination of stomach does not disclose any significantly unusual.
Embodiment
Embodiment 1
The gastric content that gives rat behind the polymeric material is observed
Have in each the comfortable Velaz T4 cage of Wistar rat of listed feature in the table 1 and under the Routine Test Lab condition, raise.Room temperature is that 20-24 ℃ and relative humidity are 30-70%.Fluorescent lamp provides every day about 12 hours illumination.Feedstuff and water container are changed weekly and are sterilized at least once.Use Lignocel (Velaz Ltd., Czech Republic) as the pad grass.
Used Wistar rat in table 1. pilot system
| Species and strain | The Wistar rat |
| Quality | Conventional |
| Age during defeated passing | 6-9 week |
| Body weight during administration | The 200-300 gram |
| The group number | 3 |
| Every group number of rats | 2 |
| The animal sum | 6 |
In domestication and research process with the granular muroid feedstuff of standard (NOE H4, Racio Breclav, CzechRepublic) any nutrition purposes, especially for feeding animals with monitoring quality (annual minimum 2 times analyze possible poisonous substance and microbial contaminations).Any water (annual minimum 2 possible poisonous substance and microbial contaminations of analysis) of supply in domestication and research process with monitoring quality.Rat is marked with picric acid solution and tamed 5 days.Experimental design and grouping are listed in respectively in table 2 and 3.
Table 2. experimental design
| Program | Date |
| The research beginning | The 1st day |
| Domestication | 5 days |
| Experimental section begins | Before 30 days |
| Physical examination | Before 31 days |
| The test piece administration begins | The 1st day |
| Dosed administration | The administration of gavage single oral |
| Postmortem at interval | 30,90 minutes |
| Body weight | Before the administration |
| The expectation of experimental section finishes | The 1st day |
Table 3. grouping
| Group # | Rat | Test |
| 1 | F1，F2 | Premedication H 2Blocker |
| 2 | F3，F4 | No forerunner's administration |
| 3 | F5，F6 | Feed is arranged |
All rats are overnight fasting all.First group of rat is at preceding 4 hours premedication H of administration
2Blocker
(10 milligrams of famotidines, Johnson; JohnsonMerck ConsumerPharmaceuticals, 1 capsule/rat).Second group does not have premedication and mustn't take food behind oral tube feed PMSF-1.The 3rd group does not have premedication, but allows to take food behind oral tube feed PMSF-1.
The PMSF-1 powder is mixed so that this material swelling with the ratio of tap water with 640 milligrams of PMSF-1/50 ml waters.Give rat 5 milliliters of swollen PMSF-1 by oral tube feed.(this rat is weighed immediately behind oral tube feed PMSF-1 and stays in the dark until postmortem for F5, F6) food to give rat in the 3rd group.Measure and write down the 3rd group food consumption.Perform an autopsy on sb according to table 4.
Table 4. postmortem stomach function regulating is at interval observed
| Animal number | H2 blocker premedication | The postmortem interval (minute) |
| F1 | Be | 90 |
| F2 | Be | 105 |
| F3 | Not | 30 |
| F4 | Not | 90 |
| F5 | Not | 70 |
| F6 | Not | 50 |
Use ether with rat euthanasia, the stomach of excision animal is also being tightened the stomach outlet in case stopping leak after leaking is weighed stomach.Then, cleaning stomach and gastric content weighed and estimate.Behind oral tube feed PMSF-1, observe any poisoning signal of rat, comprise vomiting, diarrhoea, energy and behavior change.Write down the 3rd group food consumption.The results are shown in the table 5 of the actual time of PMSF-1 administration, postmortem phase and gastric content inspection.
Table 5. stomach observed result
| Animal number | The H2 blocker | The PMSF-1 that uses (milliliter) | Food consumption (gram) | PMSF-1+food (gram) | The postmortem interval (minute) | Gastric content (gram) * | Residual content (%) |
| F1 | + | 5.00 | 0.00 | 5.00 | 90 | 1.34 | 27％ |
| F2 | + | 5.00 | 0.00 | 5.00 | 105 | 0.48 | 10％ |
| F3 | - | 5.00 | 0.00 | 5.00 | 30 | 4.08 | 82％ |
| F4 | - | 5.00 | 0.00 | 5.00 | 90 | 0.00 | 0％ |
| F5 | - | 5.00 | 2.70 | 7.70 | 70 | 6.87 | 89％ |
| F6 | - | 5.00 | 0.50 | 5.50 | 50 | 4.05 | 74％ |
*F1-F4 only comprises swollen PMSF-1.
F5 and F6 comprise the mixture of PMSF-1 and food, because the two can not separate.
The above results shows that the H2-blocker has increased PMSF-1 and kept swollen total time to measure in the animal stomach.In addition, the food of known raising stomach pH value also causes PMSF-1 to keep the swelling longer time and PMSF-1 is mixed with food.Therefore the result who obtains with food further shows, when with the PMSF-1 coupling, no matter is that the pharmacological or the reagent of trophism can improve the performance of PMSF-1 in gastric environment in nature.
Claims (136)
1. realize or improve hydrogel in the animal stomach the swelling ability and/or increase the method that described hydrogel keeps swollen time quantum under one's belt, comprise to animal giving with one or more raisings and keeping the water-swellable polymer of material associating of the microenvironment pH value of polymer and/or stomach.
2. the process of claim 1 wherein that described polymer is a super absorbent polymer.
3. the process of claim 1 wherein that described polymer is selected from homopolymer, copolymer, polymer blend, cross linked polymer, polymer composites and combination thereof.
4. the method for claim 3, wherein said polymer is a polymer composites.
5. the process of claim 1 wherein that the described material that one or more change pH value is selected from buffer agent, H
2Blocker, proton pump inhibitor, antacid, protein, nutrition bland and combination thereof.
6. the method for claim 5, wherein said buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
7. the method for claim 5, wherein said H
2Blocker is selected from Altramet, ranitidine, famotidine, nizatidine and combination thereof.
8. the method for claim 5, wherein said proton pump inhibitor is selected from omeprazole, lansoprazole, esomeprazole, pantoprazole, Lei Beila frustrates and make up.
9. the method for claim 5, wherein said antacid is selected from aluminium hydroxide, magnesium hydroxide, aluminium carbonate, calcium carbonate and brucite.
10. the method for claim 1, wherein said polymer further comprises one or more pharmaceutically acceptable excipient, is selected from plasticizer, diluent, binding agent, lubricant, coloring agent, stabilizing agent, surface-active agents, spice, antiseptic, antioxidant, buffer agent and combination thereof.
11. the method for claim 10, wherein said buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
12. the process of claim 1 wherein that described polymer is with one or more therapeutic active agents, diagnostic reagent or the administration of prophylactic activity reagent.
13. the method for claim 12, wherein said reagent are selected from analgesic, antibiotic medicine, antipyretic, antidepressants, antiepileptic medicine, hydryllin, antimigraine, anti-muscarine medicine, antianxiety drugs, tranquilizer, sleeping pill, psychosis, bronchodilator, antasthmatic, cardiovascular drug, corticosteroids, dopaminergic, electrolytes, gastrointestinal drug, muscle relaxant, nutrient, vitamin, parasympathomimetic agent, stimulant, anorexigenic, appetite suppressant, antiadipositas drug, anti-narcolepsy medicine and combination thereof.
14. the method for claim 12, wherein said reagent are appetite suppressant or antiadipositas drug.
15. the method for claim 14, wherein said appetite suppressant or antiadipositas drug are selected from Sibutramine hydrochloride, orlistat, Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.
16. the process of claim 1 wherein that the described polymer of preparation is used for oral administration.
17. the method for claim 16, wherein said preparaton are selected from tablet, capsule sheet, capsule, syrup, solution, suspension, powder, stick and bland.
18. the process of claim 1 wherein that material and the described polymer of the microenvironment pH value that improves polymer and/or stomach is with same dosage form while administration.
19. the process of claim 1 wherein that material and the described polymer of the microenvironment pH value that improves polymer and/or stomach is with different dosage form while administration.
20. the process of claim 1 wherein material administration before or after described polymeric drug delivery of the microenvironment pH value that improves polymer and/or stomach.
21. the method for claim 20, the material administration in 24 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
22. the method for claim 20, the material administration in 2 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
23. the method for claim 20, the material administration in 6 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
24. the method for claim 1 further comprises the material that gives to cause hydrogel degraded, dispersion and/or contraction after hydrogel stays for some time under one's belt.
25. the method for claim 24, the administration after polymeric drug delivery of wherein said material.
26. the method for claim 24, wherein said material are used to reduce the microenvironment pH value of polymer and/or stomach.
27. the method for claim 26, wherein said material is an organic acid.
28. the method for claim 26, wherein said material is an acidic beverages.
29. the method for claim 24, wherein said material is a protein.
30. the method for claim 29, wherein said protein is enzyme.
31. the method for claim 30, wherein said enzyme is selected from pepsin, pancreatin and combination thereof.
32. the process of claim 1 wherein that the surgical operation of described polymer and material and obesity is co-administered.
33. the method for claim 32, wherein the surgical operation of treatment of obesity is selected from gastric banding, gastric bypass, built-in gastric qi ball, the electricity irritation of implantable gastric stimulator stomach function regulating.
34. the method for claim 17, wherein said water-swellable preparaton is the optional bland form that comprises vitamin, mineral or nutriment, and it effectively improves stomach pH value with the swelling, the complementary diets nutrition that strengthen described polymer or cause satiety and lose weight.
35. the process of claim 1 wherein that described animal is primates, cattle, sheep, horse, pig, birds, rodent, felid or Canis animals.
36. the process of claim 1 wherein that described animal is human.
37., comprise to animal comprising the water-swellable polymer of medicine and the material of the microenvironment pH value of one or more raising polymer and/or animal stomach to the method for the defeated drug delivery of animal.
38. the method for claim 37, wherein said medicine discharges from polymer in the slow release mode.
39. the method for claim 37, wherein said medicine are selected from therapeutic active agents, diagnostic reagent or prophylactic activity reagent.
40. the method for claim 39, wherein said reagent are selected from analgesic, antibiotic medicine, antipyretic, antidepressants, antiepileptic medicine, hydryllin, antimigraine, anti-muscarine medicine, antianxiety drugs, tranquilizer, sleeping pill, psychosis, bronchodilator, antasthmatic, cardiovascular drug, corticosteroids, dopaminergic, electrolytes, gastrointestinal drug, muscle relaxant, nutrient, vitamin, parasympathomimetic agent, stimulant, anorexigenic, appetite suppressant, antiadipositas drug, anti-narcolepsy medicine and combination thereof.
41. the method for claim 39, wherein said reagent are appetite suppressant or antiadipositas drug.
42. the method for claim 41, wherein said appetite suppressant or antiadipositas drug are selected from Sibutramine hydrochloride, orlistat, Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.
43. the method for claim 37, wherein said polymer is a super absorbent polymer.
44. the method for claim 37, wherein said polymer is selected from homopolymer, copolymer, polymer blend, cross linked polymer, polymer composites and combination thereof.
45. the method for claim 44, wherein said polymer is a polymer composites.
46. the method for claim 37, the wherein said material that one or more change pH value is selected from buffer agent, H
2Blocker, proton pump inhibitor, antacid, protein, nutrition bland and combination thereof.
47. the method for claim 46, wherein said buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
48. the method for claim 46, wherein said H
2Blocker is selected from Altramet, ranitidine, famotidine, nizatidine and combination thereof.
49. the method for claim 46, wherein said proton pump inhibitor are selected from omeprazole, lansoprazole, esomeprazole, pantoprazole, Lei Beila frustrates and make up.
50. the method for claim 46, wherein said antacid is selected from aluminium hydroxide, magnesium hydroxide, aluminium carbonate, calcium carbonate and brucite.
51. the method for claim 37, wherein said polymer further comprises one or more pharmaceutically acceptable excipient, is selected from plasticizer, diluent, binding agent, lubricant, coloring agent, stabilizing agent, surface-active agents, spice, antiseptic, antioxidant, buffer agent and combination thereof.
52. the method for claim 51, wherein said buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
53. the method for claim 37 is wherein prepared described polymer and is used for oral administration.
54. the method for claim 53, wherein said preparaton are selected from tablet, capsule sheet, capsule, syrup, solution, suspension, powder, stick and bland.
55. the method for claim 37 wherein improves the material of microenvironment pH value of polymer and/or stomach and described polymer with same dosage form administration simultaneously.
56. the method for claim 37 wherein improves the material of microenvironment pH value of polymer and/or stomach and described polymer with different dosage form administration simultaneously.
57. the method for claim 37, the material administration before or after described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
58. the method for claim 57, the material administration in 24 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
59. the method for claim 57, the material administration in 2 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
60. the method for claim 57, the material administration in 6 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
61. the method for claim 37 further comprises the material that gives to cause hydrogel degraded, dispersion and/or contraction after hydrogel stays for some time under one's belt.
62. the method for claim 61, the administration after polymeric drug delivery of wherein said material.
63. the method for claim 61, wherein said material are used to reduce the microenvironment pH value of polymer and/or stomach.
64. the method for claim 63, wherein said material is an organic acid.
65. the method for claim 63, wherein said material is an acidic beverages.
66. the method for claim 61, wherein said material is a protein.
67. the method for claim 66, wherein said protein is enzyme.
68. the method for claim 66, wherein said enzyme is selected from pepsin, pancreatin and combination thereof.
69. the method for claim 37, the surgical operation of wherein said polymer and material and obesity is co-administered.
70. the method for claim 69, wherein the surgical operation of treatment of obesity is selected from gastric banding, gastric bypass, built-in gastric qi ball, the electricity irritation of implantable gastric stimulator stomach function regulating.
71. the method for claim 54, wherein said water-swellable preparaton is the optional bland form that comprises vitamin, mineral or nutriment, and it effectively improves stomach pH value with the swelling, the complementary diets nutrition that strengthen this polymer or cause satiety and lose weight.
72. the method for claim 37, wherein said animal are primates, cattle, sheep, horse, pig, birds, rodent, felid or Canis animals.
73. the method for claim 37, wherein said animal are human.
74. each method of claim 1-73, wherein this method is used for the treatment of obesity, causes and lose weight and/or improve gastric retention.
75. realize or improve hydrogel in the animal stomach the swelling ability and/or increase the medicament that described hydrogel keeps swollen time quantum under one's belt, it comprises with one or more raisings and keeps the water-swellable polymer of material associating of the microenvironment pH value of polymer and/or stomach.
76. the medicament of claim 75, wherein said polymer is a super absorbent polymer.
77. the medicament of claim 75, wherein said polymer is selected from homopolymer, copolymer, polymer blend, polymer composites and combination thereof.
78. the medicament of claim 77, wherein said polymer is a polymer composites.
79. the medicament of claim 75, the wherein said material that one or more change pH value is selected from buffer agent, H
2Blocker, proton pump inhibitor, antacid, protein, nutrition bland and combination thereof.
80. the medicament of claim 79, wherein said buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
81. the medicament of claim 79, wherein said H
2Blocker is selected from Altramet, ranitidine, famotidine, nizatidine and combination thereof.
82. the medicament of claim 79, wherein said proton pump inhibitor are selected from omeprazole, lansoprazole, esomeprazole, pantoprazole, Lei Beila frustrates and make up.
83. the medicament of claim 79, wherein said antacid is selected from aluminium hydroxide, magnesium hydroxide, aluminium carbonate, calcium carbonate and brucite.
84. the medicament of claim 75, wherein this medicament further comprises one or more pharmaceutically acceptable excipient, is selected from plasticizer, diluent, binding agent, lubricant, coloring agent, stabilizing agent, surface-active agents, spice, antiseptic, antioxidant, buffer agent and combination thereof.
85. the medicament of claim 84, wherein said buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
86. the medicament of claim 75, wherein this medicament further comprises one or more therapeutic active agents, diagnostic reagent or prophylactic activity reagent.
87. the medicament of claim 86, wherein said reagent are selected from analgesic, antibiotic medicine, antipyretic, antidepressants, antiepileptic medicine, hydryllin, antimigraine, anti-muscarine medicine, antianxiety drugs, tranquilizer, sleeping pill, psychosis, bronchodilator, antasthmatic, cardiovascular drug, corticosteroids, dopaminergic, electrolytes, gastrointestinal drug, muscle relaxant, nutrient, vitamin, parasympathomimetic agent, stimulant, anorexigenic, appetite suppressant, antiadipositas drug, anti-narcolepsy medicine and combination thereof.
88. the medicament of claim 86, wherein said reagent are appetite suppressant or antiadipositas drug.
89. the medicament of claim 88, wherein said appetite suppressant or antiadipositas drug are selected from Sibutramine hydrochloride, orlistat, Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.
90. the medicament of claim 75 is wherein prepared this medicament and is used for oral administration.
91. the medicament of claim 90, wherein said preparaton are selected from tablet, capsule sheet, capsule, syrup, solution, suspension, powder, stick and bland.
92. the medicament of claim 75, the material and the described polymer that wherein improve the microenvironment pH value of polymer and/or stomach are same dosage form.
93. the medicament of claim 75, the material and the described polymer that wherein improve the microenvironment pH value of polymer and/or stomach are different dosage form.
94. the medicament of claim 75 further is included in the material that causes this depolymerization, dispersion and/or contraction after described polymer stays for some time under one's belt.
95. the medicament of claim 75, wherein said material are used to reduce the microenvironment pH value of polymer and/or stomach.
96. the medicament of claim 95, wherein said material is an organic acid.
97. the medicament of claim 95, wherein said material is an acidic beverages.
98. the medicament of claim 95, wherein said material is a protein.
99. the medicament of claim 75, wherein this medicament is the optional bland form that comprises vitamin, mineral or nutriment, and it effectively improves stomach pH value with the swelling, the complementary diets nutrition that strengthen described polymer or cause satiety and lose weight.
100. be used for medicament, comprise the water-swellable polymer that contains medicine and improve the material of the microenvironment pH value of polymer and/or animal stomach with one or more to the defeated drug delivery of animal.
101. the medicament of claim 100, wherein said medicine discharges from polymer in the slow release mode.
102. the medicament of claim 100, wherein said medicine are selected from therapeutic active agents, diagnostic reagent or prophylactic activity reagent.
103. the medicament of claim 102, wherein said reagent are selected from analgesic, antibiotic medicine, antipyretic, antidepressants, antiepileptic medicine, hydryllin, antimigraine, anti-muscarine medicine, antianxiety drugs, tranquilizer, sleeping pill, psychosis, bronchodilator, antasthmatic, cardiovascular drug, corticosteroids, dopaminergic, electrolytes, gastrointestinal drug, muscle relaxant, nutrient, vitamin, parasympathomimetic agent, stimulant, anorexigenic, appetite suppressant, antiadipositas drug, anti-narcolepsy medicine and combination thereof.
104. the medicament of claim 102, wherein said reagent are appetite suppressant or antiadipositas drug.
105. the medicament of claim 104, wherein said appetite suppressant or antiadipositas drug are selected from Sibutramine hydrochloride, orlistat, Rimonabant, benzphetamine, diethylpropion, Mazindol phendimetrazine, Duromine, amphetamine, fenfluramine, nalmefene and combination thereof.
106. the medicament of claim 100, wherein said polymer is a super absorbent polymer.
107. the medicament of claim 100, wherein said polymer is selected from homopolymer, copolymer, polymer blend, cross linked polymer, polymer composites and combination thereof.
108. the medicament of claim 107, wherein said polymer is a polymer composites.
109. the medicament of claim 100, the wherein said material that one or more change pH value is selected from buffer agent, H
2Blocker, proton pump inhibitor, antacid, protein, nutrition bland and combination thereof.
110. the medicament of claim 109, wherein said buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
111. the medicament of claim 109, wherein said H
2Blocker is selected from Altramet, ranitidine, famotidine, nizatidine and combination thereof.
112. the medicament of claim 109, wherein said proton pump inhibitor are selected from omeprazole, lansoprazole, esomeprazole, pantoprazole, Lei Beila frustrates and make up.
113. the medicament of claim 109, wherein said antacid is selected from aluminium hydroxide, magnesium hydroxide, aluminium carbonate, calcium carbonate and brucite.
114. the medicament of claim 100, wherein said polymer further comprises one or more pharmaceutically acceptable excipient, is selected from plasticizer, diluent, binding agent, lubricant, coloring agent, stabilizing agent, surface-active agents, spice, antiseptic, antioxidant, buffer agent and combination thereof.
115. the medicament of claim 114, wherein said buffer agent is selected from ammonium bicarbonate, ammonium carbonate, ammonium hydroxide, sodium bicarbonate, calcium carbonate, calcium hydroxide, magnesium carbonate, potassium bicarbonate, potassium carbonate, potassium hydroxide, sodium carbonate, sodium hydroxide and combination thereof.
116. the medicament of claim 100 is wherein prepared described polymer and is used for oral administration.
117. the medicament of claim 116, wherein said preparaton are selected from tablet, capsule sheet, capsule, syrup, solution, suspension, powder, stick and bland.
118. the medicament of claim 100 wherein improves the material of microenvironment pH value of polymer and/or stomach and described polymer with same dosage form administration simultaneously.
119. the medicament of claim 100 wherein improves the material of microenvironment pH value of polymer and/or stomach and described polymer with different dosage form administration simultaneously.
120. the medicament of claim 100, the material administration before or after described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
121. the medicament of claim 120, the material administration in 24 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
122. the medicament of claim 120, the material administration in 2 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
123. the medicament of claim 120, the material administration in 6 hours of described polymeric drug delivery that wherein improves the microenvironment pH value of polymer and/or stomach.
124. the medicament of claim 100 further is included in the material that causes the hydrogel degraded after hydrogel stays for some time under one's belt, disperses and/or shrink.
125. the medicament of claim 124, the administration after polymeric drug delivery of wherein said material.
126. the medicament of claim 124, wherein said material are used to reduce the microenvironment pH value of polymer and/or stomach.
127. the medicament of claim 126, wherein said material is an organic acid.
128. the medicament of claim 126, wherein said material is an acidic beverages.
129. the medicament of claim 124, wherein said material is a protein.
130. the medicament of claim 129, wherein said protein is enzyme.
131. the medicament of claim 130, wherein said enzyme is selected from pepsin, pancreatin and combination thereof.
132. the method for claim 100, the surgical operation of wherein said medicament and obesity is co-administered.
133. the medicament of claim 132, wherein the surgical operation of treatment of obesity is selected from gastric banding, gastric bypass, built-in gastric qi ball, the electricity irritation of implantable gastric stimulator stomach function regulating.
134. the medicament of claim 117, wherein said water-swellable preparaton is the optional bland form that comprises vitamin, mineral or nutriment, and it effectively improves stomach pH value with the swelling, the complementary diets nutrition that strengthen this polymer or cause satiety and lose weight.
135. the medicament of claim 100, wherein said animal are primates, cattle, sheep, horse, pig, birds, rodent, felid or Canis animals.
136. the medicament of claim 100, wherein said animal are human.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78661506P | 2006-03-28 | 2006-03-28 | |
| US60/786,615 | 2006-03-28 | ||
| US60/787,396 | 2006-03-30 |
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| Publication Number | Publication Date |
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| CN101453987A true CN101453987A (en) | 2009-06-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800197605A Pending CN101453987A (en) | 2006-03-28 | 2007-03-28 | Use of polymeric materials with other substances for improved performance |
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| CN (1) | CN101453987A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105476735A (en) * | 2016-01-20 | 2016-04-13 | 李新民 | Semipermeable membrane water suction weight-losing stomach balloon |
| CN105815363A (en) * | 2008-11-18 | 2016-08-03 | 万有限责任公司 | Methods and compositions for weight management and for improving glycemic control |
| CN107921666A (en) * | 2015-08-31 | 2018-04-17 | 金伯利-克拉克环球有限公司 | Improve the purity of the material from disposable absorbent article recycling |
-
2007
- 2007-03-28 CN CNA2007800197605A patent/CN101453987A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105815363A (en) * | 2008-11-18 | 2016-08-03 | 万有限责任公司 | Methods and compositions for weight management and for improving glycemic control |
| CN107921666A (en) * | 2015-08-31 | 2018-04-17 | 金伯利-克拉克环球有限公司 | Improve the purity of the material from disposable absorbent article recycling |
| US10493661B2 (en) | 2015-08-31 | 2019-12-03 | Kimberly-Clark Worldwide, Inc. | Improving the purity of materials recycled from disposable absorbent articles |
| CN107921666B (en) * | 2015-08-31 | 2020-12-18 | 金伯利-克拉克环球有限公司 | Improving purity of materials recycled from disposable absorbent articles |
| CN105476735A (en) * | 2016-01-20 | 2016-04-13 | 李新民 | Semipermeable membrane water suction weight-losing stomach balloon |
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Open date: 20090610 |