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WO2001030373A1 - Composition polypeptidique - Google Patents

Composition polypeptidique Download PDF

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Publication number
WO2001030373A1
WO2001030373A1 PCT/RU2000/000427 RU0000427W WO0130373A1 WO 2001030373 A1 WO2001030373 A1 WO 2001030373A1 RU 0000427 W RU0000427 W RU 0000427W WO 0130373 A1 WO0130373 A1 WO 0130373A1
Authority
WO
WIPO (PCT)
Prior art keywords
mass
polypeptide
insulin
composition
concentration
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/RU2000/000427
Other languages
English (en)
Russian (ru)
Other versions
WO2001030373A8 (fr
Inventor
Nikolai Alfredovich Plate
Lev Ivanovich Valuev
Gennady Alexeevich Sytov
Mariya Viktorovna Uliyanova
Ljudmila Vitalievna Vanchugova
Ljudmila Konstantinovna Staroseltseva
Elena Iliinichna Shakhmatova
Nataliya Pavlovna Prutskova
Jury Viktorovich Natochin
Vladimir Alexandrovich Knyazhev
Jay Henis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institut Neftekhimicheskogo Sinteza Imeni Avto Pchieva Rossiiskoi Akademii Nauk (inkhs Ran)
Institut Neftekhimicheskogo Sinteza Imeni A V Topchieva
Original Assignee
Institut Neftekhimicheskogo Sinteza Imeni Avto Pchieva Rossiiskoi Akademii Nauk (inkhs Ran)
Institut Neftekhimicheskogo Sinteza Imeni A V Topchieva
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from RU99122655/14A external-priority patent/RU2171687C2/ru
Application filed by Institut Neftekhimicheskogo Sinteza Imeni Avto Pchieva Rossiiskoi Akademii Nauk (inkhs Ran), Institut Neftekhimicheskogo Sinteza Imeni A V Topchieva filed Critical Institut Neftekhimicheskogo Sinteza Imeni Avto Pchieva Rossiiskoi Akademii Nauk (inkhs Ran)
Priority to IL14935500A priority Critical patent/IL149355A0/xx
Priority to DE10085144T priority patent/DE10085144T1/de
Priority to AU13162/01A priority patent/AU1316201A/en
Publication of WO2001030373A1 publication Critical patent/WO2001030373A1/fr
Publication of WO2001030373A8 publication Critical patent/WO2001030373A8/fr
Priority to DK200200624A priority patent/DK200200624A/da
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/27—Growth hormone [GH], i.e. somatotropin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A61K38/56—Protease inhibitors from plants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A61K38/57—Protease inhibitors from animals; from humans

Definitions

  • the invention is subject to the field of medicine, biochemistry and biotechnology, and it is the personalized medicine used in medicine for the treatment of by-drug
  • the gastric fluid in the process of digestion passes into the duodenal ulcer, where it mixes with bile and the gastric gland.
  • the pharmaceutical products contained in the pan-therapeutic system trypsin and other hydrolyze the reaction with amine-derived substances.
  • the normal conditions of the protein are almost completely extended to Their constituent amino acids, which are then rapidly absorbed in the intestine. It is possible that some hydraulic processes (for example, in the case of illnesses) are fully completed at an intestinal rate. [. The biology of man. Russia, intersect ⁇ , 1993. p. 284-297].
  • a known polypeptide compound consisting of (% wt.) 0.001 - 0.5 polypeptides, as a rule uses insulin, 1, 0-30.0 polimerpa. modified inhibition of industrial enzymes, and 70-98 water [Patent of the Russian Federation Ya ⁇ ”2066551. ⁇ I ⁇ 61 ⁇ 38/28, BI . ⁇ . 29, 1996].
  • First use of this combination reduces the glucose level at 53% of the time when the initial insulin dose is 10 units / kg.
  • ⁇ es ⁇ the purpose ⁇ bes ⁇ echeniya v ⁇ zm ⁇ zhn ⁇ s ⁇ i ⁇ e ⁇ aln ⁇ g ⁇ ⁇ imeneniya ⁇ m ⁇ zitsii her ⁇ yvayu ⁇ zhelud ⁇ chn ⁇ - ⁇ ezis ⁇ en ⁇ n ⁇ y ⁇ b ⁇ l ⁇ ch ⁇ y, ⁇ aya not ⁇ as ⁇ v ⁇ yae ⁇ sya in zhelud ⁇ e, n ⁇ ⁇ as ⁇ v ⁇ yae ⁇ sya in ⁇ n ⁇ m ⁇ ishechni ⁇ e with vysv ⁇ b ⁇ zhdeniem ⁇ m ⁇ zitsii and s ⁇ de ⁇ zhascheg ⁇ sya it ⁇ li ⁇ e ⁇ ida.
  • the disadvantage of this combination is the complexity of its use (inability to perform gastric-impaired treatment) and a low incidence of infection.
  • the maximum decrease in the concentration of glucose at home after the introduction of a com- pensation is 47% of the original level.
  • the com- pact contains insulin, and in the capacity of inhibitors of enzymes, it inhibits the metabolism of soy.
  • the company uses it by distributing it in a physiological process (0.9% recovery of sodium chloride) to achieve a percentage increase of 0.0%. (5 mg per 10 ml) with the subsequent introduction of 1 ml of the solution is not immediately available in the intestine of the livestock.
  • the indicated product may also contain a protective polimer, antioxidant, inhibitory enzyme and non-organic salt.
  • the disadvantage of this device is the inability to use it inappropriately for the administration of a drug.
  • the composition of the product does not ensure the protection of the constituent in it from the harmful effect of the acidic environment of the stomach. Therefore, before the oral administration of the product, the patient is introduced to the body for complete neutralization of the acid of the stomach. And although the physical activity is known to be relatively high (for example, the rapid introduction of 10 units of insulin into the body with diabetes has a high incidence of fatal illness)
  • the company uses it in its use in water or in a physiological process to achieve a concentration of the substance
  • the combination may additionally contain the known compounds, which accelerate the absorption process, by a factor of 10 to 5, more than.
  • Example 1 The composition contains 15 mg of insulin (3.0% of the mass), 0.1 mg (0.02
  • a pan-therapeutic inhibitor of trypsin 470 mg (94% of the mass) of citric acid and 14.9 mg (2.98% of the mass) of lactose.
  • the molecular mass of insulin is 6500.
  • the composition is dissolved in 100 ml of physiological solution of insulin concentration equal to 0.015% of the mass) and 6.7 ml
  • the resulting solution (25 units of insulin) transfers the drug to the patient. Samples are at risk of testing and after 30, 60, 90, 120 and 150 minutes after the introduction of the drug. The results are presented in table 1.
  • the composition contains 10 mg of insulin (2.0% of the mass), 0.1 mg (0.02% of the mass) of soybean inhibitor of trypsin, 1.0 mg (0.2% of the mass) of citric acid and 488.9 mg (97, 78% of the mass) of carboxymethyl cellulose.
  • the composition is dissolved in 100 ml of a physiological solution (insulin concentration is equal to 0.01% of the mass) and 10 ml of the obtained solution (25 units of insulin) is converted. The results are presented in table 1.
  • the composition contains 10.98 mg of insulin (42.23% of the mass), 0.01 mg (0.04% of the mass) of ovomucoid from the protein of ducks, 15 mg (57.69% of the mass) of citric acid and 0.01 mg (0 , 04% of the mass) of polyvinylpyrrolide.
  • composition is distributed in 100 ml of physiological solution (concentration of insulin is equal to 0.011% of the mass) and 9.1 ml of the obtained solution (25 units of insulin) is converted.
  • concentration of insulin is equal to 0.011% of the mass
  • 9.1 ml of the obtained solution 25 units of insulin
  • composition contains 14.5 mg of insulin (15.3% of the mass), 0.2 mg
  • the composition contains 20.5 mg of insulin (97% of the mass), 0.17 mg (0.8% of the mass) of ovomucoid from the protein of duck eggs, 0.4 mg (2.0% of the mass) of citric acid and 0.04 mg ( 0.2% of the mass) of the lactose.
  • the composition is distributed in 100 ml of physiological solution (concentration of insulin is equal to 0.0205% of the mass) and 4.9 ml of the resulting solution (25 units of insulin) are converted. The results are presented in table 1.
  • Table 1 The effect of the administration of a live substance containing 1 mg of insulin in the composition of the claimed composition to the concentration of glucose in the body.
  • Whites are placed in the cage-pens for the removal of urine and within 120 minutes, the excretion of urine in the urinary tract is registered. Without the introduction of an internal load, crusts excrete 0.4 ⁇ 0.04 ml of urine per 100 g of body weight in 120 minutes. 15 and at the end of the meal, 5 ml of water per 100 g of body weight are injected into the stomach with a probe. In 120 minutes, these flavors excrete 4.42 ⁇ 0.19 ml of urine per 100 g of body weight.
  • composition contains 0.004 mg (95% of the mass) of desmopressin - polypeptide (molecular weight of 1069), which decreases the excretion of milk, 0.000042 mg (1% of the mass) of carbohydrate protein of eggs, 0.000042 mg (1%) 00013 (3% of the mass) of sugar.
  • the mixture is dissolved in 100 ml of water (the concentration of desmopressin is equal to 0.000004% of the mass) and this solution is injected into the stomach of 11 ml and the mass is 5 ml per 100 g. 120 For 120 minutes, the separation of blood from the body is 1.1 1 ⁇ 0.41 ml of urine per 100 g of body weight, that is, it will be reduced 4 times after the introduction of the drug.
  • Example 12 The composition contains 0.04 mg (93% of the mass) of desmessess,
  • the concentration is increased in 100 ml of water (concentration
  • the dispersion is equal to 0.00004%> mass) and the tests are carried out at 9th and at 7th level. For 120 minutes, the discharge at the moment is completely suppressed.
  • Example 13 The composition contains 10 mg of glucose (80%> mass), 1.25 mg of inhibitor of trypsin from soya (10% of the mass), 0.2 mg of citric acid (1.6% of the mass) and 1.05 mg of polyvinylpyridine , 4% of the mass).
  • the molecular weight of the glucone is equal to 3500.
  • the composition is dissolved in 100 ml of water (the concentration of glucogen is equal to 0.01% of the mass) and 10 ml of the solution is discharged.
  • the concentration of glucose in the blood is measured after 5, 10, 20, 30 and 60 minutes. The results are shown in table 2.
  • the composition contains 100 mg of glucagon (98% by weight), 1, 02 mg of inhibitor of trypsin from soy (1% of the mass), 0.51 mg of citric acid (0.5%> mass) and 0.51 mg of polyvinylpyrrolide (0.5%> )
  • the solution is dissolved in 100 ml of water (concentration of glucone is equal to 0.1% of the mass) and 1 ml of solution is added to the solution.
  • concentration of glucone is equal to 0.1% of the mass
  • 1 ml of solution is added to the solution. The results are shown in table 2.
  • the composition contains 15.0 mg (80% of the mass) of the growth hormone (protein with a molecular weight of 21,000), 1.58 mg (8.4%> of the mass) of ovomucoid from the protein of the utensils of eggs, 1.3 mg (6.9% of the mass) Acidic Acid and 0.88 mg (4.7% of the mass) of polyvinylpyrrolidine.
  • the composition is distributed in 100 ml of a physiological solution (concentration of the group is equal to 0.015 mass) and 6.7 ml of an increased volume (1 mg of the unit). The results are presented in table 3.
  • Example 16 The composition contains 15.0 mg (80%> mass) of the growth medium, 1.58 mg (8.4% of the mass) of the pancreatic acid inhibitor, 0.88 mg (4.7 mass) of citric acid and 1.3 mg (6.9%> mass) of lactose.
  • the composition is dissolved in 100 ml of a physiological solution (concentration of the group is equal to 0.015%> of the mass) and 6.7 ml of the obtained product is in bulk (1 mg) The results are presented in table 3.
  • the composition contains 100 mg (98% of the mass) of the growth hormone, 0.51 mg (0.5%> of the mass) of utukuida from the protein of the utensils of eggs, 0.51 mg (0.5% of the mass) of the acid and 1.0 mg (1 mg) , 0%> mass) of polyvinylpyrrolide.
  • the composition is dissolved in 100 ml of a physiological solution (concentration of the growth group is equal to 0.1%> mass) and 1.0 ml of the obtained product (1 mg of the group)
  • Table 3 Dependence of the growth rate of the hormone in the area at the time of administration after the administration of a 1 mg growth hormone.
  • the preparation for example, 1, additionally contains 150 mg of sodium lauryl sulfate.
  • the results of the test of this combination are given in table 4.
  • EXAMPLE 19 The preparation for example 1 additionally contains 750 mg of sodium lauryl sulfate. The test results of this arrangement are shown in Table 4. 14
  • the claimed invention ensures that there is no need for mass treatment of masses of up to 1000 to 21000 for industrial use.
  • polypeptides are located in a native state, which ensures their inherent physical activity.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Zoology (AREA)
  • Endocrinology (AREA)
  • Botany (AREA)
  • Diabetes (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention relève de la médecine et concerne notamment une composition polypeptidique destinée à soigner les malades par l'administration pérorale dans leur organisme de préparations médicinales polypeptidiques. La composition polypeptidique de l'invention comprend en tant que composant actif un polypeptide ayant un poids moléculaire entre 1000 et 21000, un inhibiteur de ferments protéolytiques tel qu'un inhibiteur de trypsine à base de soja, un inhibiteur pancréatique de trypsine, une aprotinine, une ovomucoïde à base du blanc d'oeuf d'oiseaux et un acide organique et une charge inerte pharmacologiquement acceptables, avec le rapport suivant des composants (en % en poids): polypeptide 1,0-95,0; inhibiteur de ferments protéolytiques 0,02 10,0; acide organique 1,0 - 94,0; charge inerte le reste. Pour augmenter l'efficacité de cette composition, on peut y inclure des substances connues qui facilitent la pénétration des polypeptides à travers la membrane des muqueuses.
PCT/RU2000/000427 1999-10-28 2000-10-27 Composition polypeptidique Ceased WO2001030373A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
IL14935500A IL149355A0 (en) 1999-10-28 2000-10-27 Polypeptide corporation
DE10085144T DE10085144T1 (de) 1999-10-28 2000-10-27 Polypeptidkomposition
AU13162/01A AU1316201A (en) 1999-10-28 2000-10-27 Polypeptide composition
DK200200624A DK200200624A (da) 1999-10-28 2002-04-25 Polypeptid-præparat

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU99122655 1999-10-28
RU99122655/14A RU2171687C2 (ru) 1999-10-28 Полипептидная композиция

Publications (2)

Publication Number Publication Date
WO2001030373A1 true WO2001030373A1 (fr) 2001-05-03
WO2001030373A8 WO2001030373A8 (fr) 2002-02-07

Family

ID=20226315

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU2000/000427 Ceased WO2001030373A1 (fr) 1999-10-28 2000-10-27 Composition polypeptidique

Country Status (6)

Country Link
AU (1) AU1316201A (fr)
DE (1) DE10085144T1 (fr)
DK (1) DK200200624A (fr)
IL (1) IL149355A0 (fr)
WO (1) WO2001030373A1 (fr)
YU (1) YU31902A (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020506882A (ja) * 2017-01-27 2020-03-05 マイクロファーム・リミテッドＭｉｃｒｏｐｈａｒｍ Ｌｉｍｉｔｅｄ 炎症性障害の治療療法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU94010369A (ru) * 1994-03-23 1996-08-10 Институт нефтехимического синтеза им. А.В.Топчиева РАН Способ получения производных инсулина
WO1996036352A1 (fr) * 1995-05-16 1996-11-21 Pankaj Modi Formulations liquides pour produits pharmaceutiques proteiniques comprenant au moins deux agents d'amelioration de l'absorption
WO1998011912A1 (fr) * 1996-09-20 1998-03-26 Neurobiological Technologies, Inc. Formulations pharmaceutiques du facteur de liberation de la corticotropine possedant une meilleure stabilite sous forme liquide
RU2126264C1 (ru) * 1993-04-07 1999-02-20 Скиос Инк. Фармацевтическая композиция
RU2136306C1 (ru) * 1994-05-04 1999-09-10 Санофи Стабилизированная протеинсодержащая лиофилизированная композиция

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2126264C1 (ru) * 1993-04-07 1999-02-20 Скиос Инк. Фармацевтическая композиция
RU94010369A (ru) * 1994-03-23 1996-08-10 Институт нефтехимического синтеза им. А.В.Топчиева РАН Способ получения производных инсулина
RU2136306C1 (ru) * 1994-05-04 1999-09-10 Санофи Стабилизированная протеинсодержащая лиофилизированная композиция
WO1996036352A1 (fr) * 1995-05-16 1996-11-21 Pankaj Modi Formulations liquides pour produits pharmaceutiques proteiniques comprenant au moins deux agents d'amelioration de l'absorption
WO1998011912A1 (fr) * 1996-09-20 1998-03-26 Neurobiological Technologies, Inc. Formulations pharmaceutiques du facteur de liberation de la corticotropine possedant une meilleure stabilite sous forme liquide

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020506882A (ja) * 2017-01-27 2020-03-05 マイクロファーム・リミテッドＭｉｃｒｏｐｈａｒｍ Ｌｉｍｉｔｅｄ 炎症性障害の治療療法
US11098114B2 (en) 2017-01-27 2021-08-24 Micropharm Limited Ovine derived human TNFα polyclonal antibody composition for oral administration
JP6997785B2 (ja) 2017-01-27 2022-02-04 マイクロファーム・リミテッド 炎症性障害の治療療法

Also Published As

Publication number Publication date
WO2001030373A8 (fr) 2002-02-07
YU31902A (sh) 2004-12-31
AU1316201A (en) 2001-05-08
IL149355A0 (en) 2002-11-10
DE10085144T1 (de) 2003-04-24
DK200200624A (da) 2002-06-21

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