前苏联专利SU1309901A3 Method of producing oxitetracycline therapeutic composition

专利PDF首页>>前苏联专利

专利附录

专利说明

权利要求

类似技术

同族专利

引用文献

法律状态

优先权

专利摘要:
1520197 Tetracycline compositions containing 2-pyrrolidone PFIZER INC 15 Dec 1976 [2 Jan 1976] 52394/76 Heading A5B A stabilised antibiotic composition comprises a solution of a chelated tetracyclin in aqueous 2-pyrrolidone, the tetracycline being selected from oxytetracycline, doxycycline, tetracycline, chlortetracycline, and the pharmaceutically acceptable acid addition salts thereof. The chelates may be those of magnesium and/or calcium. The solution may also contain 1-7% by weight of polyvinylpyrrolidone of average molecular weight of ca. 5,000 to 100,000.
公开号:SU1309901A3
申请号:SU762436954
申请日:1976-12-28
公开日:1987-05-07
发明作者:Валлесли Армстронг Вильям；Джаявантрай Десай Сорабхкумар
申请人:Пфайзер Инк (Фирма)；
IPC主号:

专利说明:

one . 1309 This invention relates to antibiotic compositions suitable for pharmacological use, In particular: this refers to aqueous solutions of oxytetracycline, doxncycline, tetracycline and chlortetracycline containing 2-pyrrolidone.
Example 1. Preparing a solution of composition, g / 100 ml: oxytetracycline (according to
with respect to the effectiveness of 927 gamma / mg Yu Sodium dehydrate for sulfoxylate for- plus 5% aging) 22.65; magnesium oxide 1,921; 2-pyrrolidone 40.00; magnesium formaldehyde sulfoxylate 0.44; 2-aminoethanol 0; ten; water up to 100 ml.
Maldehyde Magnesium produces a similar product.
Example 3. In accordance with the method of example 1, the obtained solution.
The 2-pyrrolidone was stirred to characterize the content of etherization with water, then the resulting solution was heated to about 15 ° C and the magnesium formaldehyde sulfoxylate was added and dissolved with stirring. Magnesium oxide was further added to the resulting solution and a slurry was formed. Further, slow addition of oxytetracycline was made by stirring, resulting in a clear solution. This solution was cooled to room temperature, and the pH value was adjusted to 8.5 pH units by adding 2-amino-ethanol. Then the solution was diluted with water to the required volume of 100 ml.
The indicated solution, containing 200 mg / ml of oxytetracycline (by activity), was characterized by a viscosity of 13.0 CST at 25 ° C.
The resistance of the tissue is acceptable and the blood levels are satisfactory after subcutaneous injections to the cattle.
Example5. In accordance with the method of example 1, the obtained solution.
Replacing 1 g of sulfoxylate with formaldehyde 40, characterized by the content of sodium oxytetra-dehydrate with sulfoxylate of formalracycline activity, 100 mg / ml.
magnesium dehydrate results in a similar product.
PRI mme R 2. Get the solution composition, g / 100 ml: oxytetracycline
.. (with respect to the effectiveness of 927 gamma / mg plus 5% aging; 22.65; magnesium oxide 1.921; 2-pyrrolidone 40.00; polyvinylpyrrolidone K-17
.5.00; magnesium formaldehyde sulfoxylate 0.44; 2-aminoethanol, 0.17; water up to 100 ml.
In accordance with this example, 2-pyrrolidone was agitated with water. Polyvinylpyrrolidone further; was added and stirring continued until dissolved. Further, the technique described in Example 1 was applied.
one
The resulting product, with an oxytetracycline activity of 200 mg / ml, had a viscosity of 23 hf at.
Firmness is acceptable and blood levels are satisfactory after subcutaneous and intramuscular injections to livestock.
Replacing 1 g of sodium formaldehyde sulfoxylate with a sulfoxylate
Maldehyde Magnesium produces a similar product.
Example 3. In accordance with the method of example 1, the obtained solution.
characterizing the content of oxytetra
0
five
cyclin activity 25 mg / ml, composition, g / 100 ml: oxytetracycline (relative to efficacy 927 gamma / mg plus 5% aging) 2.831; magnesium oxide 0.245; 2-pyrrolidone 10.00; formaldehyde sulfoxylate sodium 1.00; 2-aminoethanol, 0.012; water up to 100 ml.
The viscosity of the resulting solution of 2 HPS at.
Example4. In accordance with the procedure of Example I, a solution was obtained, characterized by a content of oxytetracycline activity 50 mg / ml, composition, g / 100 ml: oxytetracycline (relative to the effectiveness of 927 gamma / mg plus 5% aging) 5,662; magnesium oxide 0,490; 2-pyrrolidone 20; formaldehyde sulfoxylate sodium 1.00; 2-aminoethanol 0.065; water to) 00 ml.
The viscosity of the resulting 2.5 hfc solution at 25 s.
Example5. In accordance with the method of example 1, the obtained solution.
0 characterized by an oxytetracycline activity of 100 mg / ml.
five
0
five
composition, g / 100 ml: oxytetracycline (relative to the effectiveness of 927 gamma / mg plus 5% aging) 1 1, 325, magnesium oxide 0.48; 2-pyrrolidone 35.00; formaldehyde sulfoxylate sodium 1.00; water to 100 ml.
The viscosity of the resulting 3.0 hfc solution at.
Example In accordance with the procedure of Example 2, a solution was obtained, characterized by a content of oxytetracycline activity of 200 mg / ml, composition, g / 100 ml: oxytetracycline (relative to the effectiveness of 927 gamma / mg plus 5% aging) 22.65; magnesium oxide 1,421; 2-pyrrolidone 40.00; polyvinylpyrrolidone K-30 5.00;
Magnesium sulfoxylate formaldehyde 0.44; 2-aminoethanol 0.50; water up to 100 ml.
The viscosity of the resulting solution of 5 hfc at.
Example 7. In accordance with the method of example 2, a solution was obtained, characterized by an oxytetracycline content of 200 mg / ml, co Example II. In accordance with the method of Example 1, a solution was obtained, characterized by a content of oxetracycline activity of 350 mg / ml, composition g / 100 mp: oxytetracycline (relative to the effectiveness of 927 gamma / kg plus 5% aging) 39.597; magnesium oxide 3.43; 2-pyrrolidone 50.00; sodium formaldehyde sulfoxylate
stavat, g / 100 ml: oxytetric hydrochloride-water to 100 ml. The viscosity of semi-acyclic (with respect to the effective solution resulting from 200 STS 905 gamma / mg plus 5% aging) is 23.20; magnesium oxide 1,921; 2-pyrrolidone 40.00; polyvinylpyrrolidone K-17
5.00; Formaldehyde sulfoxylate by the method of Example 1; plant 0.44; 2-aminoethanol 3.84; a reservoir characterized by an okdo content of 100 ml. of tetracycline activity 400 mg / ml
The viscosity of the resulting composition g / 100 ml: oxytetracycline
at.
nj) HMep 12. According to
a solution of 45 sts at
ExampleB In accordance with 20. by the procedure of Example 2, a solution was obtained, characterized by an oxytetracycline activity of 200 mg / ml, composition, g / 100 ml: oxytetracycline (relative to the effectiveness of 927 gamma / mg plus 5% aging) 22.65; chloride mag (relative to efficiency 927 gamma / ml plus 5% aging J 45.30; magnesium oxide 3.92; 2-pyrrolidone 50.00; sodium formaldehyde sulfoxylate 1.00; water to 100 ml.
The viscosity of the resulting solution of 785 hfs at 25 C.
nor, hexahydrate 9,668; 2-pyrrolidone 40.00; polyvinylpyrrolidone K-17 5.00; magnesium formaldehyde sulfoxylate 0.44; 2-aminoethanol 0.88; water up to 100 ml.
The viscosity of the resulting 35 hfc solution at.
Example 9. In accordance with the method of example 1, a solution was obtained, characterized by a content of oxytetracycline activity of 200 mg / ml, composition, g / 100 ml: oxytetracycline (in relation to the effectiveness of 927 gamma / mg plus 5% aging) 22.65 magnesium acetate, tetragidrate 10.021; 2-pyrrolidone 40.00; formaldehyde sulfoxylate sodium 1.00; 2-amio-ethanol, 0.76; water up to 100 ml.
The viscosity of the resulting 33 hrs solution at.
EXAMPLE 50. In accordance with the procedure of Example 2, a solution was obtained, characterized by a 300 mg / ml content of hydroxytetracycline activity, of composition g / 100 ml: oxytetracycline (relative to
In this example, 2-pyrrolidone supplied with stirring with water, the solution thus obtained was heated to about and then sodium formaldehyde sulfoxylate was added and dissolved with stirring, addition of magnesium oxide and slurry formed with solution, slowly added to xycycline with stirring. Water. The native index was adjusted by means of concentrated hydrochloric acid. The resulting solution was cooled to room temperature, and further, the magnitude of water was 927 gamma / mg plus 5% aging) magnesium oxide 2.94; 2-pyrrolido 50.00; the native indicator is reduced to formaldehyde sulfoxylate sodium: 7.3 units. pH using concentrated 1.00; water up to 100 ml. Viscosity of semi-hydrochloric acid. This resulting CTC solution 70 was diluted to the desired
at.
9014
Example II In accordance with the method of Example 1, a solution was obtained, characterized by a content of oxetracycline activity of 350 mg / ml, composition g / 100 mp: oxytetracycline (relative to the effectiveness of 927 gamma / kg plus 5% aging) 39.597; magnesium oxide 3.43; 2-pyrrolidone 50.00; sodium formaldehyde sulfoxylate
resulting in a solution of 200 hfs
method of example 1 obtained rastpri.
nj) HMep 12. According to
(with respect to the effectiveness of 927 gamma / ml plus 5% aging J 45.30; magnesium oxide 3.92; 2-pyrrolidone 50.00; sodium formaldehyde sulfoxylate 1.00; water to 100 ml.
The viscosity of the resulting solution of 785 hfs at 25 C.
Example 13. A solution is obtained, characterized by a content of doxy- (Cyclic activity 100 mg / ml, composition, g / 100 ml: doxycycline (with respect to the effectiveness of 930 gamma / mg plus 5% aging) 11.29; magnesium oxide 1,921; 2- pyrrolidone 50.00; sodium formaldehyde sulfoxylate 1.00; concentrated hydrochloric acid in an amount sufficient to bring the pH value to 7.3 units; pH; water to 100 ml.
In this example, 2-pyrrolidone was agitated with water, the solution thus obtained was heated to approximately and then sodium formaldehyde sulfoxylate was added and dissolved with stirring, magnesia was added and sludge formation was added, and the xycline was slowly added with stirring. Water the native index was adjusted with concentrated hydrochloric acid. The resulting solution was cooled to room temperature, and then the value of water
0
five
native indicator brought to: 7.3 units. pH using concentrated hydrochloric acid. This solution was diluted to the desired
volume by adding water.
51309901 6
Solutions comparable with the above, ki 3,828; 2-pyrrolidone 30.00; sulpolucheny at values of 5.0 and 6.5 units. sodium formaldehyde phenylate 1.00;
pH, respectively.
Example 14. In accordance with
sufficient concentrated hydrochloric acid
using the procedure of Example 13, a solution was obtained, 5 to bring the value
Characterized by the content of doxycycline activity of 100 mg / ml, composition, g / 100 ml: doxycycline (in relation to the effectiveness of 930 gamma / mg plus 5% aging) 11.29; magnesium oxide 1,921; 2-pyrrolidone 40.00; sodium formaldehyde sulfoxylate 1.00; sufficient hydrochloric acid in an amount sufficient to bring the pH value to 7.2 pH units; water up to 100 ml.
A solution comparable to the above is also obtained by bringing the pH value to 5.2 units. pH
Example 15. In accordance with the procedure of Example 13, a solution was obtained with a content of doxycycline activity of 200 mg / ml, composition, g / 100 ml: doxycycline (with respect to the effectiveness of 930 gamma / mg plus 5% aging) 22.58; magnesium oxide 3,828; 2-pyrrolidone 50.00; sodium formaldehyde sulfoxylate 1.00; sufficient hydrochloric acid in an amount sufficient to bring the pH value to 7.2 units. pH; water to good
A solution comparable to this is also obtained by bringing the pH value to t 5.2 pp.
Example 16. In accordance with the procedure of Example 13, a solution was obtained with a content of doxycycline activity of 200 mg / ml, composition, g / 100 ml: doxycycline (relative to the effectiveness of 930 gamma / mg plus 5% aging) 22.581; magnesium oxide 3,828; 2-pyrrolidone 40.00; sodium formaldehyde sulfoxy lat 1.00; Concentrated hydrochloric acid in an amount sufficient to bring the pH value to 7.00 units. pH; water up to 100ml
Example 17. In accordance with the method of example 13, a solution was obtained, characterized by a content of doxycycline activity 200 mg / ml, composition, g / 100 ml; doxycycline (in relation to the effectiveness of 930 gamma / m plus 5% aging) 22.58; Magconcentric hydrochloric acid in sufficient quantity
up to 5.8 units pH; water up to 100 ml.
Example 18. A solution was obtained, characterized by a content of doxycycline activity of 200 mg / ml, composition, g / 100 ml: doxycycline (relative to the effectiveness of 930 gamma / mg plus 5% aging) 22.58; magnesium oxide 3,828; 2-pyrrolidone 40.00; sodium formaldehyde sulfoxylate 1.00; polyvinylpyrrolidone K-17 5.00; sufficient hydrochloric acid in an amount sufficient to bring the pH value to 6.6 pH units; water up to 100ml.
The 2-pyrrolidone was agitated with water and then polyvinylpyrrolidone was added and stirred until complete dissolution. Then the procedure of example 13 was repeated.
A solution comparable to this is obtained using 30 g of 2-pyrrolidone instead of 40 g.
Example 19. In accordance with the method of Example 13, a solution was obtained, characterized by a content of doxycycline activity of 100 mg / ml, composition
0
va, g / 100 ml: doxycycline hydrochloride (relative to the effectiveness of 850 gamma / mg plus 5% aging) 12,353; magnesium oxide 2.02; 2-pyrrolidone 60.00; sodium formaldehyde sulfoxylate IjOO; sufficient hydrochloric acid in an amount sufficient to bring the pH value to 7.2 unit pH} water to 100 ml.
Solutions comparable to these are also obtained by bringing the pH value to-6.5 and 5.0 units. pH, respectively.
Example number 20. In accordance with the procedure of Example 13, a solution was obtained, characterized by a content of doxycycline activity of 100 mg / ml,. composition, g / 100 ml: doxycycline (with respect to the effectiveness of 930 gamma / mg Plus 5% aging) 11.29; magnesium oxide 0.059; sulfoxylate formaldehyde
sodium 1.00; 2-pyrrolidone 70.00; an amount of concentrated hydrochloric acid sufficient for
bringing the pH value to 7.2 units. pH; "Ode to 100 ml
Solutions comparable to those obtained were also obtained by adjusting the pH to 6.5 and 5.2 units. pH, respectively.
Example 21. In accordance with the method of Example 13, a solution was obtained with a content of doxycycline activity of 10 mg / ml, composition g / 100 ml: doxycycline (with respect to the effectiveness of 930 gamma / mg plus 5% aging) 1,129; magnesium oxide: 0.206; 2-pyrrolidone 10.00; formaldehyde sulfoxylate sodium 1.00; sufficient hydrochloric acid in an amount sufficient to bring the pH value to 6.7 units. pH; water up to 100 ml.
A solution comparable to this is also prepared by adjusting the pH to 5 units. pH
Example 22. A solution was obtained, with a content of tetracycline hydrochloride with an activity of 100 mg / ml, composition, g / 100 ml: tetracycline (with respect to the effectiveness of tatracycline hydrochloride 955 gamma / mg plus 5% aging) 10.995; magnesium oxide 0.958; 2-pyrrolidone 70.00; formaldehyde sulfoxylate sodium 1.00; polyvinylpyrrolidone K-17 5.00; sufficient amount of mono-ethanolamine to bring the pH value to 8.5 units. pH; water up to 100 ml. In this example, 2-pyrrolidone was mixed with water and the resulting solution was heated to about 50 ° C, then sodium formaldehyde sulfoxylate was added and dissolved with stirring, addition of magnesium oxide and slurry formation with a solution, then slowly added tetracycline with stirring until a clear, clear solution is obtained. The resulting solution was cooled to room temperature, and then the pH value was adjusted to 8.5 units. pH using monoethanolamine. This solution was diluted to the required volume by adding water.
A solution comparable to that obtained was obtained using 60 g / 100 ml of 2-pyrrolidone instead of 70 g / 100 ml of 2-pyrrolidone.
fO
15
099018
Example 23. In accordance with the method of Example 22, a solution was obtained characterized by a content of tetracycline hydrochloride with an activity of 55 mg / ml, 5 composition, g / 100 ml: tetracycline (relative to the effectiveness of tetracycline hydrochloride 955 gamma / mg plus 5% aging) 5.496; magnesium oxide 0.479; 2-pyrrolidone 70.00; formaldehyde sulfoxylate sodium 1.00; polyvinylpyrrolidone K-15 5.00; sufficient monoethanolamine to bring the pH value to 8,, 5 units. pH; water up to 100 ml.
A solution comparable to this is also obtained by applying 50.00 g / 100 ml 2-pyrrolidone instead of 70.00 g / 100 ml.
Example 24. B according to
the method of example 22, the resulting solution,
characterized by a tetracycline hydrochloride content of 50 mg / ml
composition, g / 100 ml: tetracycline (according to the effectiveness of tetracycline. hydrochloride 955 gamma / mg plus 5% aging) 5.496; magnesium oxide 0.479; 2-pyrrolidone 60.00; sodium formaldehyde sulfoxylate 0.44; polyvinylpyrrolidone K-17 5.00; sufficient monoethanolamine to bring the pH value to 85 units. pH; water up to 100 ml.
Example 25. In accordance with the method of example 22, the resulting solution
5 characterized by the content of tetracycline hydrochloride with an activity of 100 mg / ml, the composition (except that polyvinylpyrrolidone was not used), g / 100 ml: tetracycline (by
0
0
0
five
with respect to the effectiveness of tetracycline hydrochloride 955 (gamma / mg plus 5% aging) 10.995; magnesium oxide 0.958; .2-pyrrolidone 60.00; sodium formaldehyde sulfoxylate 0.44; sufficient monoethanolamine to bring the pH value to 8.9 units. pH; water up to 100 ml.
A solution comparable to that indicated was obtained using 70.00 g / / 100 ml 2-pyrrolidone at pH 8.8 units.
Example 26. In accordance with the method of example 25, a solution was obtained characterized by a content of tetracycline hydrochloride with an activity of 50 mg / ml, composition, g / 100 ip: tetracycline (relative to the effectiveness of tetracycline hydrochloride 955 gamma / mg plus 5%
Aging) 5, A96; magnesium oxide 0.479; 2-pyrrolidone 60.00; sodium formaldehyde sulfoxylate 0.44; sufficient monoethanolamine to bring the pH value to 8.8 ppH; water up to 100 ml.
A solution comparable to that indicated was obtained using 70 g / 100 ml of 2 pyrrolidone with a pH of 8.7 pbw.
Example 27. In accordance with the procedure of Example 25, a solution was obtained, characterized by a tetracycline hydrochloride content of 100 mg / ml, composition, g / 100 ml: tetracycline hydrochloride (relative to the effectiveness of tetracycline hydrochloride 980 gamma / mg plus 5% aging) 10.714 ; magnesium oxide 0.939; 2-pyrrolidone 60.00; formaldehyde sulfoxylate sodium 1.00; sufficient monoethanolamine to bring the pH value to 8.5 units. pH; water up to 100 ml.
PRI me R 28. In accordance with the method of example 23, except that the pH value was regulated by concentrated hydrochloric acid, a solution was obtained, characterized by the content of tetracycline hydrochloride with an activity of 10 mg / ml, composition, g / 100 ml: tetracycline ( with respect to the effectiveness of tetracycline hydrochloride 955 (gamma / mg plus 5% aging) 1.099; magnesium oxide 0.096; 2-pyrrolidone 30.00; formaldehyde sulfoxylate sodium 1.00; sufficient hydrochloric acid in an amount sufficient to bring the pH value to 7.5 pH units; water up to 100ml.
Solutions comparable with the indicated ones were also obtained by bringing the pH value to 6.5 and 5.2 units. pH, respectively.
PRI me R 29. A solution was obtained, characterized by the content of chlortetracycline hydrochloride with activity, 100 mg / mp, composition, g / 100 ml: chlorotracycline hydrochloride (relative to the effectiveness of chlortetracycline hydrochloride 950 gamma / mg plus S % aging) 11,053; calcium chloride 4.96; 2-pyrrolidone 60.00; monothiogly cerin 1.00; monoethanolamine in sufficient quantity to bring
five
0
ranks of hydrogen index to 8, Ved. pH; water up to 100 ml.
In this example, 2-pyrrolidone was mixed with water, the resulting solution was heated to about and then monothioglycerol was added and dissolved with stirring, calcium chloride was added and slurry was formed with the solution, then slow addition of chloro-tetracycline hydrochloride was added with stirring, and the pH was raised using monoethanolamine to obtain a solution. The resulting solution was cooled to room temperature, and then the pH value was adjusted to 8.8 pH units with monoethanolamine. This solution was diluted to the desired volume by adding water.
Solutions comparable with the above were obtained at values of 8.0 and 9.5 units of pH, respectively.
Example 30. In accordance with the procedure of Example 29, a solution was obtained, characterized by a content of chlortetracycline hydrochloride with an activity of 100 mg / ml, composition, g / 100 ml: chlorotetracycline hydrochloride (in relation to the effect of chlortetracycline hydrochloride 950 gamma / mg plus 5% aging) 11,053; calcium chloride 9.921; 2-pyrrolidone 60.00; monothioglycerol 1.00; monoethanolamine in an amount of 5 sufficient to bring the pH value to 8.8 units. pH; water up to 100 ml.
Solutions comparable to this are also obtained by bringing the pH value to 8.0 and 9.5 units. pH, respectively.
PRI me R 31. A solution was obtained, characterized by a content of chlortetracycline hydrochloride with an activity of 50 mg / ml, composition, g / 100 ml: chlorotetracycline hydrochloride (relative to the effectiveness of chlortetracycline hydrochloride 950 gamma / mg plus 5% of aging) 5.527; calcium chloride 2.48; 2-pyrrolidone 50.00; polyvinylpyrrolidone 5.00; monothioglycerol 1.00; sufficient monoethanolamine to bring the pH value to 8.8 units. pH; water up to 100 ml.
The 2-pyrrolidone was stirred with water. Next, polyvinylpyrrolidone was added, and stirring was performed.
five
O
five
until dissolved. Then the procedure of Example 29 was repeated.
Solutions comparable to this are also obtained by bringing the pH value to 8.0 and 5.9.5 units. pH, respectively.
Example 32. In accordance with the method of Example 29, a solution was obtained, characterized by chlorotetracycline hydrochloride content of activity W 200 mg / ml, composition, g / 100 ml: chlorotetracycline hydrochloride (relative to the effectiveness of chlortetracycline hydrochloride 950 gamma / mg plus 5% Aging) 22,106; calcium chloride 9.92; 2- t5 to bring the hydrogen pyrrolidone value to 60.00; monothioglycerol index up to 8.8 pH units water to
the rank of hydrogen to 8.0 9.5 units. pH, respectively.
Example 34. In accordance with the procedure of Example 31, a solution was obtained characterized by a chlorteracyclin hydrochloride content of 100 mg / ml activity, composition, g / 100 ml: chlorine tetracycline hydrochloride (relative to the effectiveness of chlortetracycline hydrochloride 950 gamma / mg plus 5% of a hundred) 11.053 ; calcium chloride 4.96; 2-pyrrolidone 60.00; monothiogliceri 1.00; polyvinylpyrrolidone 5.00; sufficient amount of ethanolamine
1,00; sufficient monoethanolamine to bring the pH value to 8.8 units. pH; water up to 100 ml.
Solutions comparable to this are also obtained by bringing the pH value to 8.0 and 9.5 units. pH, respectively.
Example 33. In accordance with the procedure of Example 29, a solution was obtained with the content of chlortetracycline hydrochloride LLP activity mg / MD, composition, g / 100 ml: chlorotetracycline hydrochloride (relative to the effectiveness of chlortetracycline hydrochloride 950 gamma / mg plus 5% aging) 11, 05; calcium chloride 4.96; 2-pyrrbldon 70.00; monothioglycerol 1.00; monoethanolamine in an amount sufficient to bring the pH value to 8.8 pH units; water up to 100 ml. ,
Solutions comparable to the indicated ones are also obtained by finishing I.Gorn's editor.
Compiled by S. Svetlyshev
Tehred M. Khodanich Proofreader M. Demchik
Order 1808/58 Circulation 596 Subscription
VNIIPI USSR State Committee
for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5
Production and printing company, Uzhgorod, Projecto st., 4
to bring the pH value to 8.8 pH units of water to
the rank of the hydrogen index to 8.0 and 9.5 units. pH, respectively.
Example 34. In accordance with the method of Example 31, a solution was obtained, characterized by a content of chlortetracycline hydrochloride with an activity of 100 mg / ml, composition, g / 100 ml: chlorotracycline hydrochloride (relative to the effectiveness of chlortetracycline hydrochloride 950 gamma / mg plus 5% of aging) 11,053 ; calcium chloride 4.96; 2-pyrrolidone 60.00; monothioglycerol 1.00; polyvinylpyrrolidone 5.00; sufficient amount of mono-ethanolamine
100 ml.
Solutions comparable to this were obtained by adjusting the pH values to 8.0 and 9.5 pp, respectively.

权利要求:
Claims (2)
[1]
1. A method for producing an oxytetracycline therapeutic composition
including the sequential introduction of magnesium compounds, an antioxidant and oxytetracycline into an aqueous solution of 2-pyrrolidone, followed by adjusting the mixture to a pH in an alkaline medium, characterized in that an aqueous solution of 2-pyrrolidone is used in a concentration of 10-50% and the pH value is 8.5 .
[2]
2. Method 1, characterized by the fact that 1 to 7% by weight of polyvinylpyrrolidone mol% is additionally introduced into the aqueous solution of 2-pyrrolidone. m. 5000-100000.

类似技术:

公开号 | 公开日 | 专利标题

SU1309901A3|1987-05-07|Method of producing oxitetracycline therapeutic composition

DE19756388A1|1999-06-24|New 2-aryl-4-amino-6,7-di:methoxy-quinazoline derivatives useful as guanylate cyclase activators for treating cardiovascular diseases, etc.

DE2817335A1|1978-11-16|ANTIBIOTIC TETRACYCLINE CONTAINERS

RU2419435C2|2011-05-27|Agent which prevents premature ovulation

DD298400A5|1992-02-20|5-ALKYLCHINOLONCARBONSAEUREN

DE2458668A1|1975-06-26|IN 4'-POSITION N-MONOSUBSTITUTED INDOANILINE, PROCESS FOR THEIR MANUFACTURING AND THEIR APPLICATION FOR DYING KERATIN FIBERS

RU2002737C1|1993-11-15|-1-|-2-isopropylaminoethanol or physiologically acceptable acid addition salt thereof with beta-mimetic and function-stimulating effects in animals

GB1507184A|1978-04-12|1-oxapenicillin intermediates and process for their preparation

CA1290690C|1991-10-15|Method of reducing the swelling or pain associated with antibiotics compositions

SU1241986A3|1986-06-30|Method of producing benzamide derivatives,hydrochlorides thereof or optical isomers

ES2147629T3|2000-09-16|ALKENYL CARBOXYLIC ACID GUANIDINES REPLACED WITH A FLUOROPHENYL GROUP AS NA + / NH + EXCHANGE INHIBITORS, THEIR PREPARATION PROCEDURE AND THEIR USE AS A DIAGNOSTIC MEDICINE OR AGENT AS WELL AS THE CONTAINING MEDICINE.

ES472847A1|1979-10-16|2-Bromo-ergosine and its acid addition salts, method for its preparation and its application as a medicine.

US3925411A|1975-12-09|Oxotremorine antagonist

SU976837A3|1982-11-23|Method of producing substance having antibiotic action

Renzetti et al.1990|Contribution of intracellular calcium to gallbladder smooth muscle contraction

US5753636A|1998-05-19|Injection solution for intramuscular and subcutaneous administration to animals

US3057780A|1962-10-09|Method for treatment of mental disease

US2388261A|1945-11-06|Riboflavin solution

ES8106517A1|1981-08-01|10-halo-E-homoeburnane derivatives, a process for the preparation thereof, a process for the use thereof as vasodilators, and vasodilating compositions thereof

SU1186074A3|1985-10-15|Method of producing terramycin solution for injections

DE2657770A1|1977-07-14|8-AMINOCARBONYL AND SULFONYL SUBSTITUTED ERGOLINS, THEIR USE AND MANUFACTURING

CN112220743B|2021-09-07|Adrenaline injection and preparation method thereof

ES8505678A1|1985-06-01|Substituted pyridoû1,2-c¿midazoû1,2-abenzimidazoles, process for their preparation, their use and pharmaceutical preparations containing them

EP0117531A1|1984-09-05|N-|-N'-propargyl piperazine, method for its preparation and its use

DE829166C|1952-01-24|Process for the preparation of N- | glycine amide and its salts

同族专利:

公开号 | 公开日

AT345977B|1978-10-10|

DE2659152A1|1977-07-14|

FI56116B|1979-08-31|

BE849885A|1977-06-28|

JPS565368B2|1981-02-04|

IN145845B|1979-01-06|

AR209242A1|1977-03-31|

NL166620C|1981-09-15|

IE44767B1|1982-03-24|

JPS5290616A|1977-07-30|

US4081528A|1978-03-28|

CA1072012A|1980-02-19|

BG36493A3|1984-11-15|

SE7613959L|1977-07-03|

PT66017B|1978-06-19|

US4086332A|1978-04-25|

DE2659152C2|1984-04-05|

DK584676A|1977-07-03|

ZA767689B|1977-12-28|

US4018889A|1977-04-19|

FI56116C|1979-12-10|

FI763716A|1977-07-03|

NL166620B|1981-04-15|

ATA971776A|1978-02-15|

AU2057176A|1978-09-28|

GR65305B|1980-08-01|

CH616080A5|1980-03-14|

OA05524A|1981-04-30|

NL7614470A|1977-07-05|

CS205030B2|1981-04-30|

CA1075603A|1980-04-15|

KR810000900B1|1981-08-19|

FR2336937A1|1977-07-29|

FR2336937B1|1980-06-27|

KE3166A|1981-11-06|

EG12291A|1978-09-30|

GB1520197A|1978-08-02|

DK145753B|1983-02-21|

PT66017A|1977-01-01|

LU76493A1|1977-07-05|

SE435997B|1984-11-05|

HK30181A|1981-07-10|

IE44767L|1977-07-02|

DK145753C|1983-08-08|

DD129997A5|1978-03-01|

引用文献:

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

GB805026A|1956-03-02|1958-11-26|Konink Nl Gisten Spiritusfabri|Process for enhancing the solubility of medicines in water|

GB802111A|1956-09-25|1958-10-01|Irwin Irville Lubowe|Improved non-toxic pesticidal compositions|

US2990331A|1956-11-23|1961-06-27|Pfizer & Co C|Stable solutions of salts of tetracyclines for parenteral administration|

DE1091287B|1957-04-09|1960-10-20|Byk Gulden Lomberg Chem Fab|Process for the production of stable, aqueous solutions of tyrothricin and subtilin|

US2980584A|1957-10-29|1961-04-18|Pfizer & Co C|Parenteral magnesium oxytetracycline acetic or lactic acid carboxamide vehicle preparation|

US2987437A|1958-03-06|1961-06-06|Gen Aniline & Film Corp|Nematocidal composition|

US3062717A|1958-12-11|1962-11-06|Pfizer & Co C|Intramuscular calcium tetracycline acetic or lactic acid carboxamide vehicle preparation|

NL6607516A|1966-05-31|1967-12-01|

US3957972A|1966-05-31|1976-05-18|Koninklijke Nederlandsche Gist-En Spiritusfabriek N.V.|Stable solutions of oxytetracycline suitable for parenteral and peroral administration and process of preparation|

DE1767891C3|1968-06-28|1980-10-30|Pfizer|Process for the preparation of aqueous medicinal solutions for parenteral, peroral and local use containing a tetracycline derivative|

US3957980A|1972-10-26|1976-05-18|Pfizer Inc.|Doxycycline parenteral compositions|

GB1508601A|1974-01-19|1978-04-26|Norbrook Labor Ltd|Oxytetracycline solution|

DK138974C|1974-02-19|1979-05-07|Ciba-Geigy Ag|

US3932653A|1974-12-19|1976-01-13|Nelson Research & Development Co.|Composition and method for topical administration of griseofulvin|

US3957994A|1974-12-19|1976-05-18|Nelson Research & Development Company|Topical anti-inflammatory composition and method of use|

US3969516A|1974-12-19|1976-07-13|Nelson Research & Development Company|Composition and method for treatment of acne|

GB1538903A|1975-04-11|1979-01-24|Nelson Res & Dev|Carrier for a topically applied physiologically active agent or cosmetic agent|US4126680A|1977-04-27|1978-11-21|Pfizer Inc.|Tetracycline antibiotic compositions|

EP0009559B1|1978-08-01|1982-08-25|Ciba-Geigy Ag|Stable, liquid pharmaceutical formulation, its preparation and use|

EP0012496B1|1978-12-08|1983-07-20|Beecham Group Plc|A process for the preparation of a solid sodium amoxycillin and aqueous solutions thereof|

US4259331A|1979-04-16|1981-03-31|Pfizer Inc.|Oxytetracycline compositions|

DE3064250D1|1979-07-02|1983-08-25|Pfizer|Long acting sulfonamide injectable compositions|

US4374826A|1980-07-21|1983-02-22|Pfizer Inc.|Sulfonamide compositions|

US4303643A|1979-07-05|1981-12-01|Pfizer Inc.|Sulfonamide compositions|

DE3063763D1|1979-07-05|1983-07-21|Pfizer|Sulfonamide solutions|

US4386083A|1980-04-10|1983-05-31|Walter Hacke|Injectable oxytetracycline compositions|

CA1163197A|1980-04-10|1984-03-06|Herman Horn|Injectable oxytetracycline compositions|

US4399127A|1980-04-10|1983-08-16|Diamond Shamrock Corporation|Injectable oxytetracycline compositions|

NL178941C|1982-06-15|1986-06-16|Aesculaap Bv|PROCESS FOR PREPARING AN AQUEOUS OXYTETRACYCLINE PREPARATION.|

US6756365B2|1991-11-06|2004-06-29|Trustees Of Tufts College|Reducing tetracycline resistance in living cells|

US4769232A|1984-03-22|1988-09-06|Pfizer Inc.|Parenteral formulations of indolmycin|

IE74244B1|1985-10-01|1997-07-16|Bimeda Res Dev Ltd|A process for preparing an antibiotic composition|

HU194493B|1985-11-27|1988-02-29|Chinoin Gyogyszer Es Vegyeszet|Process for preparing primycin-containing colloidal basic gel and compositions comprising the same|

FR2608044B1|1986-12-10|1992-09-11|Sogeval|AQUEOUS ANTIBIOTIC COMPOSITION FOR VETERINARY USE|

US4906475A|1988-02-16|1990-03-06|Paco Pharmaceutical Services|Estradiol transdermal delivery system|

EP0626171A1|1993-05-26|1994-11-30|Winfried Dörnhöfer|Oxytetracycline or doxycycline injectable solution containing PVP and N-methylpyrrolidone and/or 2-pyrrolidone|

ES2130069B1|1997-04-10|2000-03-01|Basf Labiana S A|PHARMACEUTICAL PREPARATION WITH DELAYED RELEASE OF THE ACTIVE PRODUCT.|

US20020077276A1|1999-04-27|2002-06-20|Fredeking Terry M.|Compositions and methods for treating hemorrhagic virus infections and other disorders|

US20050143353A1|2000-07-07|2005-06-30|Paratek Pharmaceuticals, Inc.|13-Substituted methacycline compounds|

US8106225B2|1999-09-14|2012-01-31|Trustees Of Tufts College|Methods of preparing substituted tetracyclines with transition metal-based chemistries|

CN1399627A|1999-09-14|2003-02-26|塔夫茨大学信托人|Method of preparing substituted tetracyclines with transition metal-based chemistries|

US6500812B2|1999-09-14|2002-12-31|Paratek Pharmaceuticals, Inc.|13-substituted methacycline compounds|

US6849615B2|1999-09-14|2005-02-01|Paratek Pharmaceuticals, Inc.|13-substituted methacycline compounds|

US20030153585A1|2000-01-13|2003-08-14|Sven-Alexander Schreder|Pharmaceutical preparations containing 2-pyrrolidone as the dissolving intermediary|

US6833365B2|2000-01-24|2004-12-21|Trustees Of Tufts College|Tetracycline compounds for treatment of Cryptosporidium parvum related disorders|

CA2404628A1|2000-03-31|2001-10-11|Stuart B. Levy|7-and 9-carbamate, urea, thiourea, thiocarbamate, and heteroaryl-amino substituted tetracycline compounds|

AU5970101A|2000-05-15|2001-11-26|Paratek Pharm Innc|7-substituted fused ring tetracycline compounds|

US20020132798A1|2000-06-16|2002-09-19|Nelson Mark L.|7-phenyl-substituted tetracycline compounds|

US20040224927A1|2000-06-16|2004-11-11|Trustees Of Tufts College|7-N-substituted phenyl tetracycline compounds|

US20020128238A1|2000-06-16|2002-09-12|Nelson Mark L.|7-phenyl-substituted tetracycline compounds|

US7553828B2|2001-03-13|2009-06-30|Paratek Pharmaceuticals, Inc.|9-aminomethyl substituted minocycline compounds|

KR101027625B1|2000-07-07|2011-04-06|파라테크 파마슈티컬스, 인크.|7-substituted tetracycline compounds|

CA2415172A1|2000-07-07|2002-01-17|Mark L. Nelson|13-substituted methacycline compounds|

US7094806B2|2000-07-07|2006-08-22|Trustees Of Tufts College|7, 8 and 9-substituted tetracycline compounds|

CZ303702B6|2000-07-07|2013-03-20|Trustees Of Tufts College|Minocycline compounds|

JP4963771B2|2000-07-07|2012-06-27|トラスティーズ・オブ・タフツ・カレッジ|7,8 and 9-substituted tetracycline compounds|

EA201000388A1|2001-03-13|2010-10-29|Пэрэтек Фамэсьютикэлс, Инк.|SUBSTITUTED TETRACYCLINE COMPOUNDS , PHARMACEUTICAL COMPOSITION AND METHOD FOR THE TREATMENT OF TETRACYCLINE-SENSITIVE CONDITION OF THE SUBJECT|

AU2002250331A1|2001-03-13|2002-09-24|Paratek Pharmaceuticals, Inc.|7-pyrollyl tetracycline compounds and methods of use thereof|

EP1241160A1|2001-03-13|2002-09-18|Glaxo Group Limited|Tetracycline derivatives and their use as antibiotic agents|

WO2002072022A2|2001-03-14|2002-09-19|Paratek Pharmaceuticals, Inc.|Substituted tetracycline compounds as antifungal agents|

CA2440757A1|2001-03-14|2002-09-19|Michael Draper|Substituted tetracycline compounds as synergistic antifungal agents|

ES2338994T3|2001-04-24|2010-05-14|Paratek Pharmaceuticals, Inc.|TETRACICLINE SUBSTITUTED COMPOUNDS FOR THE TREATMENT OF MALARIA.|

US8088820B2|2001-04-24|2012-01-03|Paratek Pharmaceuticals, Inc.|Substituted tetracycline compounds for the treatment of malaria|

US20030181371A1|2001-12-28|2003-09-25|Angiotech Pharmaceuticals, Inc.|Compositions and methods of using collajolie|

AU2003235759A1|2002-01-08|2003-07-24|Paratek Pharmaceuticals, Inc.|4-dedimethylamino tetracycline compounds|

KR101163937B1|2002-03-08|2012-07-09|파라테크 파마슈티컬스, 인크.|Amino-Methyl Substituted Tetracycline Compounds|

EA200401232A1|2002-03-21|2005-12-29|Пэрэтек Фамэсьютикэлс, Инк.|SUBSTITUTED COMPOUNDS OF TETRACYCLINE, PHARMACEUTICAL COMPOSITION AND METHOD OF TREATMENT OF TETRACYCLINE-SENSITIVE CONDITION IN SUBJECT|

US6958161B2|2002-04-12|2005-10-25|F H Faulding & Co Limited|Modified release coated drug preparation|

CN1700922A|2002-07-12|2005-11-23|帕拉特克药品公司|3, 10, and 12a substituted tetracycline compounds|

CA2502464A1|2002-10-24|2004-05-06|Paratek Pharmaceuticals, Inc.|Substituted tetracycline compounds for the treatment of malaria|

CN1732023A|2002-12-27|2006-02-08|血管技术国际股份公司|Compositions and methods of using collajolie|

EA201100956A1|2003-07-09|2012-01-30|Пэрэтек Фамэсьютикэлс, Инк.|SUBSTITUTED TETRACYCLINE COMPOUNDS , PHARMACEUTICAL COMPOSITION AND METHOD FOR TREATMENT OF TETRACYCLINE-SENSITIVE CONDITION IN SUBJECT|

WO2005009944A1|2003-07-09|2005-02-03|Paratek Pharmaceuticals, Inc.|Prodrugs of 9-aminomethyl tetracycline compounds|

US20060287283A1|2003-07-09|2006-12-21|Paratek Pharmaceuticals, Inc.|Prodrugs of 9-aminomethyl tetracycline compounds|

CN103040773A|2003-07-25|2013-04-17|沃纳奇尔科特有限责任公司|Doxycycline metal complex in a solid dosage form|

JP5010284B2|2004-01-15|2012-08-29|パラテックファーマシューティカルズインコーポレイテッド|Aromatic A-ring derivatives of tetracycline compounds|

EP2284153A3|2004-10-25|2012-03-14|Paratek Pharmaceuticals, Inc.|Substituted tetracycline compounds|

EP2301916A3|2004-10-25|2011-09-28|Paratek Pharmaceuticals, Inc.|4-aminotetracyclines and methods of use thereof|

CN103919732A|2005-01-21|2014-07-16|沃纳奇尔科特有限责任公司|A Tetracycline Metal Complex In A Solid Dosage Form|

EP1848685A1|2005-02-04|2007-10-31|Paratek Pharmaceuticals, Inc.|11a, 12-derivatives of tetracycline compounds|

US7919483B2|2005-06-24|2011-04-05|Medicis Pharmaceutical Corporation|Method for the treatment of acne|

US8722650B1|2005-06-24|2014-05-13|Medicis Pharmaceutical Corporation|Extended-release minocycline dosage forms|

JP2009502809A|2005-07-21|2009-01-29|パラテックファーマシューティカルズインコーポレイテッド|10-Substituted Tetracycline and Method of Use|

WO2007087416A2|2006-01-24|2007-08-02|Paratek Pharaceuticals, Inc.|Methods of increasing oral bioavailability of tetracyclines|

US20070244335A1|2006-04-17|2007-10-18|Teva Pharmaceutical Industries Ltd.|Isolation of tetracycline derivatives|

US8198470B2|2006-04-24|2012-06-12|Teva Pharmaceutical Industries Ltd.|Crystalline form II of tigecycline and processes for preparation thereof|

US7871993B2|2006-04-24|2011-01-18|Teva Pharmaceutical Industries Ltd.|Tigecycline crystalline forms and processes for preparation thereof|

AU2007249696A1|2006-05-15|2007-11-22|Paratek Pharmaceuticals, Inc.|Methods of regulating expression of genes or of gene products using substituted tetracycline compounds|

WO2008045507A2|2006-10-11|2008-04-17|Paratek Pharmaceuticals, Inc.|Substituted tetracycline compounds for treatment of bacillus anthracis infections|

PL2109602T3|2006-12-21|2014-09-30|Paratek Pharm Innc|Tetracycline derivatives for the treatment of bacterial, viral and parasitic infections|

ES2701725T3|2006-12-21|2019-02-25|Paratek Pharm Innc|Compounds of substituted tetracycline for the treatment of inflammatory skin disorders|

US20080242642A1|2007-04-02|2008-10-02|Medicis Pharmaceutical Corporation|Minocycline oral dosage forms for the treatment of acne|

US8252776B2|2007-04-02|2012-08-28|Medicis Pharmaceutical Corporation|Minocycline oral dosage forms for the treatment of acne|

US20080241197A1|2007-04-02|2008-10-02|Medicis Pharmaceutical Corporation|Minocycline dosage forms for the treatment of acne|

US7541347B2|2007-04-02|2009-06-02|Medicis Pharmaceutical Coropration|Minocycline oral dosage forms for the treatment of acne|

US7544373B2|2007-04-02|2009-06-09|Medicis Pharmaceutical Corporation|Minocycline oral dosage forms for the treatment of acne|

US20080241235A1|2007-04-02|2008-10-02|Medicis Pharmaceutical Corporation|Minocycline oral dosage forms for the treatment of acne|

AU2008239606A1|2007-04-12|2008-10-23|Paratek Pharmaceuticals, Inc.|Methods for treating spinal muscular atrophy using tetracycline compounds|

EP2213655A1|2007-04-27|2010-08-04|Paratek Pharmaceuticals, Inc.|Methods For Purifying Aminoalkyl Tetracycline Compounds|

AT555079T|2007-07-06|2012-05-15|Paratek Pharm Innc|PROCESS FOR SYNTHESIS OF 9-SUBSTITUTED MINOCYCLINE|

JP2011513404A|2008-03-05|2011-04-28|パラテックファーマシューティカルズインコーポレイテッド|Minocycline compounds and methods of use thereof|

PT2271348T|2008-03-28|2018-04-16|Paratek Pharm Innc|Oral tablet formulation of tetracycline compound|

US20100022483A1|2008-04-14|2010-01-28|Paratek Pharmaceuticals, Inc.|Substituted Tetracycline Compounds|

US9192615B2|2008-08-06|2015-11-24|Medicis Pharmaceutical Corporation|Method for the treatment of acne and certain dosage forms thereof|

KR20110081197A|2008-09-19|2011-07-13|파라테크 파마슈티컬스, 인크.|Tetracycline compounds for the treatment of rheumatoid arthritis and related methods of treatment|

JP2012523438A|2009-04-10|2012-10-04|タフツメディカルセンターインコーポレイテッド|PAR-1 activation by metalloproteinase-1 |

JP6025712B2|2010-05-12|2016-11-16|レンペックス・ファーマシューティカルズ・インコーポレイテッド|Tetracycline composition|

CA2835876C|2011-05-12|2020-04-14|Paratek Pharmaceuticals, Inc.|Crystalline salts of -4-dimethylamino-3,10,12,12a-tetrahydroxy-7-[amino)-methyl]-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-naphthacene-2-carboxylic acid amide and methods of using the same|

US9561241B1|2011-06-28|2017-02-07|Medicis Pharmaceutical Corporation|Gastroretentive dosage forms for minocycline|

WO2015021387A2|2013-08-09|2015-02-12|Britt George N|Formulations for control and prevention of periodontal and perimplant diseases and other diseases and conditions of the mouth, and supra and sub-gingival delivery methods and systems for such formulations|

CN103536530A|2013-10-30|2014-01-29|王玉万|Doxycycline hydrochloride long-acting injection and preparation method|

CA2980527A1|2015-03-23|2016-09-29|BioPharmX, Inc.|Pharmaceutical tetracycline composition for dermatological use|

CN104721133B|2015-04-14|2018-05-18|四川美嘉龙生物科技有限公司|A kind of terramycin preparation and preparation method|

MX2019005070A|2016-11-01|2019-09-23|Paratek Pharm Innc|9-aminomethyl minocycline compounds and use thereof in treating community-acquired bacterial pneumonia .|

US20200222432A1|2017-07-21|2020-07-16|Almirall, Llc.|Treatment of non-inflammatory lesions|

法律状态:

优先权:

申请号 | 申请日 | 专利标题

US05/646,295|US4018889A|1976-01-02|1976-01-02|Oxytetracycline compositions|

CA268,177A|CA1075603A|1976-01-02|1976-12-17|Stable solutions of doxycycline in aqueous 2-pyrrolidone|

KR7700012A|KR810000900B1|1976-01-02|1977-01-06|Process for preparing stable antibiotic composition|

[返回顶部]