CN101495143A - Pharmaceutical preparation for the treatment of obesity, diabetes and diseases associated with impaired glucose tolerance - Google Patents
Pharmaceutical preparation for the treatment of obesity, diabetes and diseases associated with impaired glucose tolerance Download PDFInfo
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- CN101495143A CN101495143A CNA2007800282985A CN200780028298A CN101495143A CN 101495143 A CN101495143 A CN 101495143A CN A2007800282985 A CNA2007800282985 A CN A2007800282985A CN 200780028298 A CN200780028298 A CN 200780028298A CN 101495143 A CN101495143 A CN 101495143A
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- 235000020824 obesity Nutrition 0.000 title claims abstract description 11
- 208000002705 Glucose Intolerance Diseases 0.000 title claims abstract description 10
- 201000009104 prediabetes syndrome Diseases 0.000 title claims abstract description 10
- 239000000825 pharmaceutical preparation Substances 0.000 title description 2
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The pharmaceutical formulations of the invention comprise antibodies to the beta-subunit of the activated insulin receptor, produced by repeated serial dilutions and external action according to homeopathic techniques. The process of the present invention for the preparation of solid pharmaceutical formulations for the oral treatment of obesity, diabetes and other diseases associated with impaired glucose tolerance comprises mixing an effective amount of a carrier with pharmaceutically acceptable additives and drying at a temperature equal to or less than 35 ℃, followed by granulation of the mixture obtained by direct dry compression, wherein the carrier is sprayed in a fluidized layer with an aqueous-alcoholic dilution of an antibody to the beta-subunit of the activated insulin receptor produced by combining repeated serial dilutions such that the antibody concentration is reduced and external effects according to homeopathic techniques are produced.
Description
Technical field
The present invention relates to field of medicaments and can be used for effective treatment and prevention of obesity, diabetes and the other diseases relevant with impaired glucose tolerance.
Background technology
Based on existing knowledge, the medicinal drug (medicament) that is used for the treatment of obesity, diabetes and the other diseases relevant with impaired glucose tolerance be known (for example, referring to Register of MedicinalDrugs of Russia " Encyclopedia of the Drugs ", 14
ThEdition, Moscow, Registerof Medicinal Drugs (RMD), 2006, pp.223-226.pp.329-332, P.510, P.731).
Yet, use these medicines not supply the steadying hand, particularly owing to toleration to them; In addition, it may follow side effect.
The method that obtains the oral form of medical solid also is known, and it comprises suppresses (RU 2203054C2, A61K9/20,2003) with the dry powder component that comprises active substance and pharmacy acceptable additive.
Yet these class methods are not suitable for making the medicinal drug that comprises antibody because its with the preparation of the liquid dosage form that is used to inject and for bioavailability is provided through parenteral.
Summary of the invention
The present invention relates to be used to develop effective medicine based on antibody, this medicine is used for oral medication obesity, diabetes and the other diseases relevant with impaired glucose tolerance and has no side effect, and the method for producing described medicine with solid dosage forms.
The solution of this task guaranteed by following true institute, i.e. the oral drugs that the present invention is used for the treatment of diabetes and the other diseases treatment relevant with impaired glucose tolerance comprise the antibody of the Insulin receptor INSR β-subunit of the activated form that obtains by multiple serial dilution with according to the external action of homeopathic therapeutic method's technology.
This medicinal drug (medicament) comprises monoclonal antibody, polyclonal antibody, recombinant antibodies, immune antibody or the natural antibody of the Insulin receptor INSR β-subunit of activated form.
In addition, this medicinal drug comprises the mixture of the different homeopathic therapeutic method's dilutions of Insulin receptor INSR β-subunit antibody of activated form.
The solution of this task is also guaranteed by following true institute, it is the production method that the present invention is used for the treatment of the Peroral solid dosage form form of diabetes and the other diseases relevant with impaired glucose tolerance, comprise that carrier with effective dose mixes with the pharmacy acceptable additive and this mixture is granulated subsequently by direct dry-pressing, wherein said carrier is poured in the fluid bed by the pure water diluent mixing of combination activated form insulin β-subunit antibody, wherein said activated form insulin β-subunit antibody is by multiple serial dilution being reduced antibody concentration and obtain according to the external action of homeopathic therapeutic method's technology, and at the temperature drying that is no more than 35 ℃.
Lactose with 150-250 μ M particle diameter is used as the carrier of this method that obtains described solid medicinal form.
Experiment confirm oral administration and by multiple serial dilution with mainly according to the medicinal drug of the Insulin receptor INSR β subunit antibody of the external action preparation of homeopathic therapeutic method's technology, provide the physiological processes that Insulin receptor INSR β-subunit is mediated especially to the regulating action of the specific impaired glucose metabolism of obesity, diabetes or the like, this treatment of guaranteeing the present patent application medicinal drug is renderd a service.
Medicinal drug prepared in accordance with the present invention is the novel medicine based on antibody, it is characterized in that specific pharmacological activity, efficient; Have no side effect, ecological purity and low cost.
The specific embodiment
Prepare this medicinal drug with following method.
Be no less than 3 amino acid residues insulin human receptor β-subunit (No.P06213 among the protein sequence Swissprot data base,
Http:// www.ncbi.hlm.nih.gov/entrez/viewer.fcgi? db=protein﹠amp; Val=33112647) fragment, especially C-terminal fragment amino acid/11 366-1382 (GGKKNGRILTLPRSNPS) as the immunogen of laboratory animal immunity to produce the polyclone immune antibody or to be used for hybridoma technology to produce recombinant monoclonal and polyclonal antibody.Antibody by the affinitive layer purification acquisition.The mixture of different fragments can be used as immunogen.
The immunity and monoclonal antibody method for example at the book Immunologicalmethods that edits by G.Frimel, Moscow, Medicina, 1987, describe among the pp.9-33.
The method that natural antibody produces is described in the book " Natural antibodies to low-molecularcompounds " M.A.Myagkova, Moscow, MGUL, 2001 (ISBN 5-8135-0058-8), pp.70-114.
The method that recombinant antibodies produces is described in Laffly E., in the paper of Sodoyer R., and Hum.Antibodies.Monoclonal and recombinant antibodies 30 years after.2005-14 volume .1-2 phase .pp.33-55.
Isolated antibody for example is generally mechanical treatment according to hahnemannian reinforcement technique (referring to Homeopathic medicinaldrugs.Guidelines on description and manufacturing.V.Shvabe through continuous and multiple dilution-its concentration of reduction and with what it carried out the outside, Moscow, 1967, pp.12-38; Or G.Keller, Homeopathy, Moscow, Medicina, 2000, part 1, pp.37-40).Initial substance (antibody) serial dilution by 1 part of volume is in the neutral flux-distilled water and/or 70% ethanol of 9 parts of volumes (being used for ten times D dilution) or 99 parts of volumes (being used for the C dilution of Radix Achyranthis Bidentatae) or 999 parts of volumes (being used for thousand times dilution), and to the every part of diluent that is obtained carry out repeatedly vertical oscillation and container that every part of diluent utilization is subsequently separated substantially until realizing desired dilution, reduce and carry out stable concentration.
Ultrasonic, electromagnetism or other physical effect are used in the external treatment in the concentration reduction process.
Can utilize the mixture of different homeopathic therapeutic method's diluents for the therapeutical effect that improves medicine.
The water that obtains or the diluent of alcoholic solution form can be used as the preparation that oral administration enters the liquid dosage form of (with the drop form) in the body or is used for Peroral solid dosage form form subsequently.
In the Huttlin Pilotlab type fluid bed that for example Huttlin GmbH makes, produce the stage of the solid dosage forms that is used for oral medication, pour in fluid bed according to the prepared neutral substance granule-lactose with 150-250 μ M particle diameter of aforementioned techniques (lactose (milk sugar)), it uses the pure water diluent (preferred Radix Achyranthis Bidentatae dilution) of the Insulin receptor INSR β-subunit antibody of activated form and carries out drying being no more than under 35 ℃ the temperature simultaneously.
" saturated " lactose of the preparation of amount of calculation is loaded into to mix thinks highly of and mix with microcrystalline Cellulose that 10.0-15.0 quality % with total Weight Loaded gives." unsaturated " lactose is added in the mixture (to reduce price and the concentration by reducing tablet Chinese materia medica material but do not reduce treatment to render a service and be convenient to a little and accelerate technological process if desired: the pure water of antibody activation type dilutes) with the 30-80 quality % of total Weight Loaded and magnesium stearate is the 0.8-1.2 quality % of total Weight Loaded subsequently, and with they even stirrings.
The uniform drying mixture that obtains is provided to the granulation machine, and for example tablet-compacting Korsch-XL400 forms the tablet of about 150-500mg to utilize direct dry pressing.
Embodiment 1.
Patient K, 62 years old, three grades of obesities (Body Mass Index 36) suffered from insulin-dependent/non-dependent diabetes for a long time.He absorbs hypoglycemic medicine (last month, the dosage with 10mg/ days absorbed glibenclamide).Under the background that glibenclamide is taken in, hypoglycemia periodically takes place, and the patient complains headache, dizzy etc.The multi-clone rabbit antibody of glibenclamide and Insulin receptor INSR β-subunit (mixture of homeopathic therapeutic method's diluent C12+C30+C200) is united with twice oral each 5 dosed administration every day.Do not register hypoglycemic case, glucose tolerance normalization during the 4-week treatment.The patient stops to absorb glibenclamide after the treatment of 1 first quarter moon, and glucose level is within normal range.Body Mass Index is reduced to 33.Recommend the pharmacotherapy of continuation based on antibody.
Embodiment 2.
Patient M, 46 years old, complaint was easy to fatigue.Check and show that it is the secondary obesity.Recommend: with 1-every day of homeopathic therapeutic method's diluent C30 " saturated " of antibody-Insulin receptor INSR β-subunit monoclonal antibody of strengthening three times.6-week, drug administration caused losing weight 7% and the improvement of natural tolerance.
Embodiment 3.
Patient K, 36 years old, complaint insomnia, food intake increasing, dyspnea.Check and show three grades of obesities, Body Mass Index 41kg/m
2Absorption comprises each 2 of twice of medicine-every day of the tablet form of Insulin receptor INSR β-subunit antibody (mixture of homeopathic therapeutic method's diluent C12+C30+C200)-make appetite normalization and reduction BMI to 36kg/m in 4 weeks
2
Embodiment 4.
Patient D 43 years old, stands a series of Bariatrics.Complain invalid Diet Therapy.5-week with every day 4 each dosed administrations of 1 comprise the medicine of Insulin receptor INSR β-subunit antibody of homeopathic therapeutic method's diluent C200, make and reduce weight in patients 10%.
Embodiment 5.
Suffering from streptozotocin-inductive diabetes far is the antidiabetic drug activity that research comprises the pharmaceutical aqueous solution of activated form Insulin receptor INSR β-subunit rabbit polyclonal antibody (mixture of homeopathic therapeutic method's diluent C12+C30+C200) in the hybridization male rat model.With the dosage intragastric administration medicine of every rat 2.5mL/kg 50 days.Insulin (through subcutaneous Actrapid HM, 12 units/kd/ days) and glibenclamide (MP Biomedical was with oral 8mg/kg/ days dosage) are as control drug.The result shows that this medicine surpasses a kind of remarkable activity of control drug.At the 7th day of treatment, blood and urine glucose level significantly reduced glucose tolerance normalization.Almost reach normal value the 14th day these parameters.Whole 50 days of drug effect continued treatment.Insulin and glibenclamide administration provide above-mentioned parameter antidiabetic drug effect in various degree; Yet action intensity is obviously lower than the animal groups of accepting Insulin receptor INSR β-subunit antibody activated form.
Embodiment 6.
Patient M 15 years old, is diagnosed as type i diabetes, disease persistent period-7 year.Because following recommendation is carried out in the reduction that insulin treatment is renderd a service (long-term insulin medicament): 1 of activated form insulin human receptor β-subunit monoclonal murine antibody (mixture of homeopathic therapeutic method's diluent C12+C30+C200)-Orally dissolving 2 times/day.After the 2-week treatment, insulin treatment is renderd a service and is significantly improved; Because insulin dose was reduced to 0.3 unit/kg/ days from 0.5 unit/kg/ days.Further (3 middle of the month), the highest reduction of insulin dose reached 0.1 unit/kg/ days.
Embodiment 7.
Patient S, 53 years old, BMI 30, suffered from insulin-dependent/non-dependent diabetes 8 years, presented the diabetic foot syndrome.The excision in the past in 1 year of right lower limb big toe.The patient complains and cuts off on the right lower limb in toe zone ulcer do not fully recover (1.5 months).The designated rabbit polyclonal antibody (mixture of homeopathic therapeutic method's diluent D6+C30+C50) of patient with 1 dosage every day (this tablet must be dissolved in the oral cavity) end user's Insulin receptor INSR β-subunit.The process of registration ulcer recovery from illness after three weeks, insulin resistance reduces.Patient's ingestion of drugs 3 months, it causes the stable of glucohemia.Notice that the significant body weight of patient reduces (IMT is reduced to 28).
Embodiment 8.
Patient Z 72 years old, complains the insulin-dependent/non-dependent diabetes of inferior compensatory.Recommendation is with oral 1, the recombinant human antibody of insulin human receptor β-subunit among homeopathic therapeutic method's diluent C30 of 3 times/day dosage.Hyperglycemia reduces after 7 days, glucose level normalization after two weeks, and the health toleration improves.
Embodiment 9.
Patient D 8 years old, worked to be diagnosed as type i diabetes in 5 years old.The disease process fast development.Under the situation that allows blood glucose 20mmol/l, this patient accepts the biosynthetic human insulin of 30 units/sky dosage.Recommend the absorption of the Insulin receptor INSR β-subunit C-terminal fragment multi-clone rabbit antibody (mixture of homeopathic therapeutic method's diluent C12+C30+C200) of 22 times/day (tablet must be dissolved in the oral cavity) dosage; With the identical dosage insulin that continues medication.Blood glucose is reduced to 15.5mmol/l in the treatment in 3 days; Glucose level normalization and maintenance are stable in the treatment of 2 weeks.The improvement that is realized makes that insulin dose is reduced to 10 unit/skies and becomes possibility in initial back 3 months of treatment.Recommend it to continue treatment.
Embodiment 10
Patient A, 51 years old.Endocrine doctor observes it for a long time for suffering from the mistake compensatory type i diabetes of nephropathy, neuropathy, skin lesion and retinopathy sign.Except that insulin treatment, be its administration very low dose Insulin receptor INSR β-subunit sheep polyclonal antibody (mixture of homeopathic therapeutic method's diluent C12+C30+C200) with 13 times/day dosage (tablet must be dissolved in the oral cavity).Skin pruritus and albuminuria (from 0.4g/L to 0.1g/L) significantly reduce after two weeks, and the skin ulcer on the lower limb is almost fully recovered.Notice the conventional condition improvement of this patient, dyspnea reduces, and work capacity improves.Recommend to prolong this treatment to reduce the dosage of injection of insulin.
Claims (5)
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| RU2006119655/15A RU2438707C2 (en) | 2006-06-06 | 2006-06-06 | Medication for per oral treatment of diabetes mellitus and other diseases accompanied by disturbance of tolerance to glucose, and method of obtaining hard drug form for per oral therapy of diabetes mellitus and other diseases, accompanied by disturbance of tolerance to glucose |
| RU2006119655 | 2006-06-06 | ||
| RU2006119658 | 2006-06-06 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103119061A (en) * | 2010-07-21 | 2013-05-22 | 奥列格·伊里奇·爱泼斯坦 | Ways to treat attention deficit hyperactivity disorder |
| CN103118707A (en) * | 2010-07-21 | 2013-05-22 | 奥列格·伊里奇·爱泼斯坦 | Composite pharmaceutical composition and method for treating diabetes and metabolic disorders |
| CN103124742A (en) * | 2010-07-15 | 2013-05-29 | 奥列格·伊里奇·爱泼斯坦 | Pharmaceutical compositions and methods of treatment |
| CN103282384A (en) * | 2010-07-15 | 2013-09-04 | 奥列格·伊里奇·爱泼斯坦 | Compound pharmaceutical composition and method for treating genitourinary system disorders |
| US9308275B2 (en) | 2010-07-15 | 2016-04-12 | Oleg Iliich Epshtein | Method of increasing the effect of an activated-potentiated form of an antibody |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2013111962A (en) | 2013-03-18 | 2014-09-27 | Олег Ильич Эпштейн | METHOD FOR DETERMINING THE EXPRESSION OF MODIFICATION ACTIVITY ASSOCIATED WITH A CARRIER |
| RU2013111961A (en) | 2013-03-18 | 2014-09-27 | Олег Ильич Эпштейн | METHOD FOR DETERMINING THE EXPRESSION OF MODIFICATION ACTIVITY ASSOCIATED WITH A CARRIER |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU1812595A (en) * | 1994-02-28 | 1995-09-11 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Cell lines for the identification of substances affecting insulin receptor mediated signal transduction |
| US5861266A (en) * | 1994-02-28 | 1999-01-19 | New York University | Treatment of diabetes mellitus and insulin receptor signal transduction |
| RU2205025C1 (en) * | 2001-12-26 | 2003-05-27 | Гольдберг Евгений Данилович | Method of correction of immune response and medicinal agent |
| RU2199345C1 (en) * | 2001-12-26 | 2003-02-27 | Эпштейн Олег Ильич | Medicinal agent and method of regulation of carbohydrate and lipid metabolism |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103124742A (en) * | 2010-07-15 | 2013-05-29 | 奥列格·伊里奇·爱泼斯坦 | Pharmaceutical compositions and methods of treatment |
| CN103282384A (en) * | 2010-07-15 | 2013-09-04 | 奥列格·伊里奇·爱泼斯坦 | Compound pharmaceutical composition and method for treating genitourinary system disorders |
| US8865163B2 (en) | 2010-07-15 | 2014-10-21 | Oleg I. Epshtein | Pharmaceutical compositions and methods of treatment |
| US9308275B2 (en) | 2010-07-15 | 2016-04-12 | Oleg Iliich Epshtein | Method of increasing the effect of an activated-potentiated form of an antibody |
| CN103119061A (en) * | 2010-07-21 | 2013-05-22 | 奥列格·伊里奇·爱泼斯坦 | Ways to treat attention deficit hyperactivity disorder |
| CN103118707A (en) * | 2010-07-21 | 2013-05-22 | 奥列格·伊里奇·爱泼斯坦 | Composite pharmaceutical composition and method for treating diabetes and metabolic disorders |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2006119655A (en) | 2007-12-27 |
| UA98621C2 (en) | 2012-06-11 |
| RU2438707C2 (en) | 2012-01-10 |
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