CN117618338A - Stable orlistat medicine water solution and preparation method thereof - Google Patents

Stable orlistat medicine water solution and preparation method thereof Download PDF

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CN117618338A
CN117618338A CN202210981782.6A CN202210981782A CN117618338A CN 117618338 A CN117618338 A CN 117618338A CN 202210981782 A CN202210981782 A CN 202210981782A CN 117618338 A CN117618338 A CN 117618338A
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streptococcus
staphylococcus
bacteroides
haemophilus
enterococcus
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朱逸凡
范敏华
赵振坤
陆平
徐沧朔
石慧
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Zhejiang Poly Pharmaceutical Co ltd
Hainan Poly Pharm Co ltd
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Zhejiang Poly Pharmaceutical Co ltd
Hainan Poly Pharm Co ltd
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Priority to PCT/CN2023/112556 priority patent/WO2024037451A1/en
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Abstract

The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a stable aqueous solution of an olanzapine drug and a preparation method thereof, wherein the aqueous solution of the olanzapine comprises the following components: orlivancin or pharmaceutically acceptable salt thereof, N-methyl-D-alanine, and water. The aqueous solution of the oritavancin drug provided by the invention takes N-methyl-D-alanine as a stabilizer, greatly reduces the growth rate of impurities in the aqueous solution at 25 ℃, and the impurity change is less than 0.1% after 30 days; high safety and high stability, and the maximum impurity content is less than 0.1% even if the product is stored at normal temperature. It is a stable ready-to-use injection.

Description

Stable orlistat medicine water solution and preparation method thereof
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a stable aqueous solution of an olanzapine drug and a preparation method thereof.
Background
Oritavancin (Oritavancin) chemical name is: [4"R ]]-22-O-(3-amino-2,3,6-trideoxy-3-C-methyl-α-Larabino-hexopyranosyl)-N3-[(4’-chloro[1,1’-biphenyl]-4-yl)methyl]vancomycin phosphate[1:2][salt]The molecular formula is: c (C) 86 H 97 N 10 O 26 C l3 ·2H 3 PO 4 The molecular weight is: 1989.09 its phosphate form has the structural formula:
oritavancin (Oritavancin) is a novel semisynthetic lipopeptide antibiotic. Oriwaxs have been shown to be effective in treating adult patients 18 years and older suffering from acute bacterial skin infections and skin structure infections (ABSSSI) caused or suspected to be caused by sensitive isolates of designated gram positive microorganisms. The current preparation of oritavancin is a freeze-dried powder injection, and requires at least one dilution before use, is inconvenient for clinical use and is prone to errors.
CN 106620649A discloses that oritavancin shows significant activity against many bacteria. This application text describes methods of treating, preventing and preventing bacterial infections and diseases in animals, including humans, using single doses of oritavancin during a course of treatment.
CN108712909a discloses a lyophilized powder formulation comprising orivancin and a beta-cyclodextrin derivative.
CN105641679a provides a stable orlistat pharmaceutical composition: oridancin, mannitol, phosphoric acid and water for injection. But is preferably in the form of a lyophilized powder for injection.
The orlistat is only marketed as freeze-dried powder injection and used for intravenous injection in abroad. The oridanin freeze-dried powder injection shows rapid degradation during reconstitution, and the oridanin aqueous solution also shows degradation during short storage, so the oridanin is not suitable for long-term storage in the aqueous solution. Therefore, a Ready-To-Use injection (RTU) is continuously developed, and compared with a freeze-dried powder injection, the RTU can be directly used clinically without a re-dissolution step, and the medication error is reduced.
Disclosure of Invention
In order to solve the problems in the prior art, the invention adopts N-methyl-D-alanine as a stabilizer, can reduce the degradation rate of the orlistat in the aqueous solution, and prepares the stable aqueous solution preparation of the orlistat. The invention provides a stable aqueous solution of an olanzapine drug, comprising the following components: orlivancin or pharmaceutically acceptable salt thereof, N-methyl-D-alanine, and water.
The pharmaceutically acceptable salts are, for example, acid salts and/or base salts, which salts may be formed with inorganic and organic acids to form pharmaceutically acceptable acid addition salts. Inorganic acids from which salts may be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts may be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. The base salts may be formed as pharmaceutically acceptable salts using inorganic and organic bases. Inorganic bases from which salts may be derived include, for example, bases containing sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like; particularly preferred are ammonium, potassium, sodium, calcium and magnesium salts. In some embodiments, treatment of the orivancin with an inorganic base loses labile hydrogen from the orivancin to provide a solution comprising inorganic cations (such as li+, na+, k+, mg) 2+ And Ca 2+ Etc.). Organic bases from which salts may be derived include, for example, primary, secondary and tertiary amines, substituted amines, cyclic amines, basic ion exchange resins, and the like, such as, inter alia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine and ethanolamine.
Wherein the content of said oritavancin or pharmaceutically acceptable salt thereof is 0.1-30% w/w, preferably 0.1-25% w/w, preferably 0.1-20% w/w, preferably 0.1-15% w/w, preferably 0.1-10% w/w, further preferably 0.1-5% w/w.
Wherein the N-methyl-D-alanine content is 0.1-60% w/w, preferably 0.5-60% w/w, further preferably 1-60% w/w.
Furthermore, an organic solvent can be added into the aqueous solution of the orivancin drug, and the organic solvent can be commonly used in liquid preparations, such as ethanol, glycerol, propylene glycol, dimethyl sulfoxide and polyethylene glycol.
The aqueous solution formulation of the oritavancin preferably has a pH of 3 to 8, more preferably 4 to 7. In particular embodiments, the pH of the final aqueous preparation of oritavancin is about 1, about 1.5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, or about 8; preferably about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7.
The aqueous solution of the oritavancin drug can further comprise one or a combination of more than two of solubilizer, surfactant, buffer, antioxidant, preservative and chelating agent.
The solubilizer is selected from ionic surfactant or nonionic surfactant, such as sodium dodecyl sulfate, tween 80, span 20, etc., and the dosage thereof is usually 0.01-20.0 g/100mL. The solubilizers are described herein by way of example only and are not intended to limit the scope of the present invention. Any suitable solubilizing agent known to those skilled in the art is suitable for use in the present invention.
Various buffers and methods may be used for adjusting the pH, including acetate buffers, citrate buffers, phosphate buffers, tartrate buffers, amino acid salts, and borate buffers. Acids or bases may be used to adjust the pH of these formulations as desired.
Such antioxidants include, but are not limited to, sodium metabisulfite, sodium thiosulfate, acetylcysteine, butylated hydroxyanisole, and butylated hydroxytoluene. The amount is usually 0.001 to 5.0g/100mL.
The preservative includes, but is not limited to, one or more of benzalkonium chloride, polyhexamethylene chloride (PHMB), chlorobutanol, thimerosal, phenylmercuric chloride, acetate, phenylmercuric nitrate, ethylparaben, parabens, benzoic acid and salts thereof, sorbic acid, chlorobutanol, benzyl alcohol, phenethyl alcohol, chlorhexidine acetate, and quaternary ammonium compound cationic surfactants, typically in an amount of 0.005 to 10.0g/100mL. The preservative is described herein by way of example only and is not intended to limit the scope of the invention. Any suitable preservative known to those skilled in the art is suitable for use in the present invention.
The chelating agents include various dicarboxylic, tricarboxylic and aminopolycarboxylic acids, such as ethylenediamine tetraacetic acid (EDTA), ethylene glycol-bis (β -aminoethyl ether) -N, N' -tetraacetic acid (EGTA) and penta (carboxymethyl) Diethylenetriamine (DTPA), and salts and hydrates thereof; monomeric polyacids such as EDTA, cyclohexanediamine tetraacetic acid (CDTA), hydroxyethylethylenediamine triacetic acid (HEDTA), diethylenetriamine pentaacetic acid (DTPA), dimercaptopropane sulfonic acid (DMPS), dimercaptosuccinic acid (DMSA), aminotrimethylene phosphonic acid (ATPA), citric acid, ophthalmically acceptable salts thereof, and combinations of any of the foregoing may also be included. Other suitable chelators include pyrophosphates, triphosphates and hexametaphosphate, chelated antibiotics such as chloroquine and tetracyclines, nitrogen-containing chelators containing two or more chelated nitrogen atoms within the imino group or in the aromatic ring (e.g., diimine, 2' -bipyridine, etc.), and various polyamines such as cyclamine (Cyclam) (1,4,7,11-tetraazacyclotetradecane), N- (C1 to C30 alkyl) -substituted cyclamine (e.g., hexadecyl cyclamine, tetramethyl hexadecyl cyclamine), diethylenetriamine (DETA), spermine, diethyl norspermine (DENSPM), diethyl homospermine (DEHOP), and deferoxamine (N ' - [5- [ [5- (acetylhydroxyamino) pentyl ] amino ] -1, 4-dioxobutyl ] hydroxy-amino ] pentyl ] -N ' - (5-aminopentyl) -N-hydroxybutyl diamide, typically in amounts of 0.01 to 5.0g/100mL.
In another aspect of the invention, a preparation method of an olanzapine medicine aqueous solution is provided, wherein the preparation method comprises the steps of weighing N-methyl-D-alanine with a prescription dose, adding the N-methyl-D-alanine into water, stirring to dissolve, weighing the oritavancin with the prescription dose, and stirring to dissolve to obtain the oritavancin medicine aqueous solution.
In the presence of other excipients, further comprising the step of adding other excipients including, but not limited to, the solubilizing agents, surfactants, buffers, antioxidants, preservatives, chelating agents and combinations of any two or more thereof.
The aqueous solution of the oridanin disclosed herein can be oral liquid, injection, eye drops, external gel, external emulsion and spray.
Administration of the formulations prepared from the aqueous solutions of the oritavancin drug disclosed herein may be via any acceptable mode of administration for agents having similar uses, including, but not limited to, oral, subcutaneous, intravenous, intranasal, topical, transdermal, intraperitoneal, intramuscular, intrapulmonary, vaginal, rectal, or intraocular administration.
The invention also provides application of the oritavancin drug aqueous solution in preparation of drugs for treating bacterial infection. The infection may be in any tissue or tissue of the subject. For example, the aqueous solution of olanzapine provided by the present invention may be used to treat a subject suffering from: blood flow infections (BSIs), catheter related blood flow infections (CRBSIs), osteomyelitis, prosthetic joint infections, pneumonia, joint space infections, and device infections.
The aqueous solution of the oritavancin drug provided by the invention can be used for treating a subject suffering from the following infection: complex skin infections and skin structure infections (cSSSI) and complex and uncomplicated skin infections and soft tissue infections (SSTI), including abscesses, ulcers, burns, cellulitis, deep bacterial infections (such as severe abscesses, infectious ulcers, severe burns, or deep and extensive cellulitis). The treatment methods may also be carried out with surgery for bacterial infection.
In some specific embodiments, the subject may be an animal, e.g., a mammal, a human.
Examples of bacterial infections include Pseudomonas aeruginosa (Pseudomonas aeruginosa), pseudomonas fluorescens (Pseudomonas fluorescens), pseudomonas acidovorans (Pseudomonas acidovorans), pseudomonas alcaligenes (Pseudomonas alcaligenes), pseudomonas putida (Pseudomonas putida), pseudomonas maltophilia (Stenotrophomonas maltophilia), burkholderia cepacia (Burkholderia cepacia), aeromonas hydrophila (Aeromonas hydrophilia), escherichia coli (Escherichia coli), citrobacter freundii (Citrobacter freundii), salmonella typhimurium (Salmonella typhimurium), salmonella typhimurium (Salmonella typhi), salmonella paratyphi (Salmonella paratyphi), salmonella enteritidis, shigella dysenteriae (Shigella dysenteriae), shigella flexneri (Shigella flexneri) Shigella sonnei (Shigella sonnei), enterobacter cloacae (Enterobacter cloacae), enterobacter aerogenes (Enterobacter aerogenes), klebsiella pneumoniae (Klebsiella pneumoniae), klebsiella oxytoca (Klebsiella oxytoc), serratia marcescens (Serratia marcescens), franciscensis (Francisella tularensis), morganella morganii (Morganella morganii), proteusmirabilis (Proteusmirabilis), proteus vulgaris (Proteus vulgaris), providencia alcalifaciens (providens), providencia rex (Providencia rettgeri), providencia sii (Providencia stuartii), acinetobacter baumannii (Acinetobacter baumannii), acinetobacter calcoaceticus (Acinetobacter calcoaceticus), acinetobacter haemolyticus (Acinetobacter haemolyticus), yersinia enterocolitica (Yersinia enterocolitica), yersinia pestis (Yersinia pestis), yersinia pseudotuberculosis (Yersinia pseudotuberculosis), yersinia intermedia (Yersinia), bordetella pertussis (Bordetella pertussis), bordetella parapertussis (Bordetella parapertussis), bordetella bronchiseptica (Bordetella bronchiseptica), haemophilus influenzae (Haemophilus influenzae), haemophilus parainfluenza (Haemophilus parainfluenzae), haemophilus haemolyticus (Haemophilus haemolyticus), haemophilus parahaemolyticus (Pasteurella multocida), basidiomycetes haemophilus dukoti (Pasteurella haemolytica), bullera catarrhalis (Branhamella catarrhalis), helicobacter pylori (Helicobacter pylori), campylobacter fetus (Campylobacter fetus), campylobacter jejuni (Campylobacter jejuni), campylobacter coli (4846), bolborospirochete (Borrelia burgdorferi), haemophilus cholerae (Vibrio), haemophilus parahaemolyticus (Haemophilus influenzae), legionella spp (35A), legionella spp (35) and Metropellae (35A), legionella spp (35) are provided by the genus Legionella (35A), legionella (35) and the genus Legionella (35A) are provided by the genus Legionella (35) and the genus Legionella (35) including the genus Legionella (35A), the genus Legionella (35) and the genus Legionella (35), bacteroides vulnificus (Bacteroides ovalus), bacteroides thetaiotaomicron (Bacteroides thetaiotaomicron), bacteroides simplex (Bacteroides uniformis), bacteroides elmendocina (Bacteroides eggerthii), bacteroides visceral (Bacteroides splanchnicus), clostridium difficile (Clostridium difficile), mycobacterium tuberculosis (Mycobacterium tuberculosis), mycobacterium avium (Mycobacterium avium), mycobacterium intracellulare (Mycobacterium intracellulare), mycobacterium leprae (Mycobacterium leprae), corynebacterium diphtheriae (Corynebacterium diphtheriae), corynebacterium ulcerans (Corynebacterium ulcerans), streptococcus pneumoniae (Corynebacterium ulcerans), streptococcus agalactiae (Corynebacterium ulcerans), streptococcus pyogenes (Corynebacterium ulcerans), streptococcus intermedius (Corynebacterium ulcerans), streptococcus dysgalactiae (Corynebacterium ulcerans), enterococcus faecalis (Corynebacterium ulcerans), enterococcus faecium (enterococcus), enterococcus (vancomycin-Corynebacterium ulcerans), enterococcus (Corynebacterium ulcerans), staphylococcus aureus (Corynebacterium ulcerans), and vancomycin-37, and vancomycin-resistant Staphylococcus (Corynebacterium ulcerans), vancomycin heterogeneously moderately resistant Staphylococcus aureus (vancomycin hetero-intermediate Staphylococcus aureus), staphylococcus epidermidis (Staphylococcus epidermidis), staphylococcus saprophyticus (Staphylococcus saprophyticus), staphylococcus intermedia (Staphylococcus intermedius), staphylococcus hyicussubsp. Hyicus, staphylococcus hemolyticus (Staphylococcus haemolyticus), staphylococcus hominis (Staphylococcus hominis), or Staphylococcus saccharolyticus (Staphylococcus saccharolyticus), and combinations thereof.
The bacterial infection treated by the aqueous solution of olanzapine provided by the present invention may be caused by any of the phenotypes or genotypes of bacteria provided above, or by any other bacteria described above that are capable of causing a bacterial infection. In the present invention, the infection being treated may be caused by more than one bacterial species, or by more than one phenotype or genotype of a single bacterial species. For example, the infection treated may be a complex skin infection and a skin structure infection.
The invention obtains the aqueous solution of the olanzapine medicine on the basis of a large number of experiments, takes N-methyl-D-alanine as a stabilizer, and has the following beneficial effects: the method provided by the invention has the advantages that the growth speed of impurities in the aqueous solution is greatly reduced under the condition of 25 ℃, and the impurity change is less than 0.1% after 30 days; high safety and high stability, and the maximum impurity content is less than 0.1% even if the product is stored at normal temperature. The injection is a Ready-To-Use (RTU) with good stability, and compared with a freeze-dried powder injection, the RTU can be directly used clinically without a re-dissolution step, and the medication error is reduced.
Drawings
FIG. 1 is a 25-60 day HPLC chart of prescription 17.
FIG. 2 is a 25-60 day HPLC chart of prescription 16.
FIG. 3 is a 25-60 day HPLC chart of prescription 15.
Detailed Description
The invention will be further described in connection with specific embodiments, but the invention is not limited thereto.
The HPLC method used for detecting the stability of the olanzapine comprises the following steps:
solution a: precisely measuring 4.0ml of triethylamine, adding water to 2000ml, and regulating the pH to 3.20 by phosphoric acid;
solution B: acetonitrile-tetrahydrofuran-solution a=55-10-935, phosphoric acid adjusted pH to 3.20;
solution C: acetonitrile-tetrahydrofuran-solution a=290-10-700, phosphoric acid adjusted to pH 3.20;
elution gradient:
Time Solution B(％) Solution C(％)
0 100 0
12 100 0
20 0 100
23 100 0
32 100 0
example 1: stability of formulations of oritavancin and different amino acids and derivatives thereof
The preparation method comprises the following steps:
1. weighing amino acid or its derivative in a prescribed amount in a beaker, adding water in the prescribed amount, and stirring to dissolve;
2. weighing the formula amount of the orlistat, and stirring for dissolution;
3. after a certain time at 25℃the sample was taken and tested, the percentage relative to the initial was calculated and the results were as follows.
Total impurities Prescription 1 Prescription 2 Prescription 3 Prescription 4 Prescription 5 Prescription 6 Prescription 7
Day 0 98.3％ 98.2％ 98.5％ 98.0％ 99.0％ 98.3％ 98.9％
For 30 days 90.1％ 92.3％ 89.3％ 84.0％ 97.6％ 94.4％ 95.9％
As can be seen from the above results, the addition of the amino acid or derivative thereof reduces the degradation of the Orliwan star in aqueous solution, reduces the increase of total impurities, and increases its stability, wherein N-methyl-D-alanine is most effective, with a relative purity of 98.6, which is the ratio of the purity after a period of time to the initial purity, for example, the relative purity of formula 5 is 97.6%/99.0%.
Example 2: stability of olanzapine and different organic solvent formulations
The preparation method comprises the following steps:
1. weighing a prescribed amount of organic solvent in a beaker, adding the organic solvent into 50ml of water for injection, and stirring to dissolve the organic solvent;
2. weighing the formula amount of the orlistat, and stirring for dissolution;
3. after a certain time at 25℃the sample was taken and tested, the percentage relative to the initial was calculated and the results were as follows.
The above results show that the crystal precipitation of the orlistat is achieved by adding a small amount of N, N dimethylacetamide, polyethylene glycol 400, propylene glycol and ethanol into the formula of the orlistat aqueous solution, which indicates that the physical compatibility of the orlistat with the above organic solvents is poor. In lower concentrations of glycerol, flocculent precipitate did not appear, but there was limited inhibition of degradation of the olympic cycle.
Experimental example 3: effect of different concentrations of stabilizers on stability of the oritavancin prescription
The preparation method comprises the following steps:
1. weighing a prescribed amount of organic solvent in a beaker, adding the organic solvent into 50ml of water for injection, and stirring to dissolve the organic solvent;
2. weighing the formula amount of the orlistat, and stirring for dissolution;
3. after being placed at 25 ℃ for a certain period of time, the sample is taken and detected, and the peak area percentage is calculated according to area normalization, and the result is as follows.
Total impurities Prescription 14 Prescription 15 Prescription 16 Prescription 17
Day 0 98.0％ 98.5％ 98.9％ 99.1％
For 30 days 97.8％ 98.2％ 98.5％ 99.6％
For 60 days 97.9％ 98.1％ 98.5％ 99.0％
The above results show that formulations 14-17 are less degraded within 60 days and remain stable for a longer period of time than formulation 1, an aqueous solution of olympic vancin, in the presence of stabilizer N-methyl-D-alanine at different ratios. FIG. 1 is a prescription 17, 25-60 day HPLC profile, integration data as follows:
fig. 2 is a prescription 16, 25-60 day HPLC profile, integration data as follows:
fig. 3 is a prescription 15, 25-60 day HPLC profile, integration data as follows:
example 4: stability of formulations of different concentrations of oritavancin and N-methyl-D-alanine
The preparation method comprises the following steps:
1. weighing N-methyl-D-alanine with a prescription amount in a beaker, adding water with the prescription amount, and stirring to dissolve;
2. weighing the formula amount of the orlistat, and stirring for dissolution;
3. after a certain time at 25℃the sample was taken and tested, the percentage relative to the initial was calculated and the results were as follows.
Total impurities Prescription 18 Prescription 19 Prescription 20 Location 21 Prescription 22 Prescription 23
Day 0 99.1％ 98.9％ 98.7％ 98.2％ 98.6％ 98.6％
For 30 days 98.8％ 98.1％ 98.0％ 97.9％ 97.5％ 96.5％
The above results show that the addition of N-methyl-D-alanine can reduce the degradation of the oritavancin with different concentrations in the aqueous solution, reduce the increase of total impurities and increase the stability of the oritavancin.
Example 5: stability of the formulations with different organic solvents after addition of stabilizers to olanzapine
The preparation method comprises the following steps:
1. weighing a prescribed amount of organic solvent and N-methyl-D-alanine or N-acetyl-D-alanine in a beaker, adding the mixture into 50ml of water for injection, and stirring the mixture to dissolve the mixture;
2. weighing the formula amount of the orlistat, and stirring for dissolution;
3. after a certain time at 25℃the sample was taken and tested, the percentage relative to the initial was calculated and the results were as follows.
The above results show that, in the formula of the aqueous solution of the olympic games, a small amount of N, N dimethylacetamide, polyethylene glycol 400, propylene glycol and ethanol are added, the olympic games are crystallized out originally, but the improvement effect is obvious after the stabilizer is added, but the improvement effect of N-acetyl-D-alanine is not obvious, the improvement effect of N-methyl-D-alanine is obvious, and the degradation of the olympic games can be inhibited.

Claims (11)

1. A stable aqueous solution of an orlistat drug comprising the components: orlivancin or pharmaceutically acceptable salt thereof, N-methyl-D-alanine, and water.
2. The aqueous pharmaceutical solution of claim 1, wherein the pharmaceutically acceptable salt is a hydrochloride or base salt.
3. The aqueous pharmaceutical solution according to claim 1, wherein the content of the olympic games or pharmaceutically acceptable salts thereof is 0.1-30% w/w, preferably 0.1-25% w/w, preferably 0.1-20% w/w, preferably 0.1-15% w/w, preferably 0.1-10% w/w, further preferably 0.1-5% w/w.
4. The aqueous pharmaceutical solution according to claim 1, wherein the N-methyl-D-alanine content is 0.1-60% w/w, preferably 0.5-60% w/w, further preferably 1-60% w/w.
5. The aqueous pharmaceutical solution of claim 1, further comprising an organic solvent selected from, but not limited to, ethanol, glycerol, propylene glycol, dimethyl sulfoxide, polyethylene glycol.
6. The aqueous pharmaceutical solution according to claims 1-5, having a pH of 3-8.
7. The aqueous pharmaceutical solution of claim 6, further comprising one or a combination of any two or more of a solubilizer, a surfactant, a buffer, an antioxidant, a preservative, and a chelating agent.
8. The method for preparing an aqueous pharmaceutical solution according to any one of claims 1 to 7, wherein the prescribed amount of N-methyl-D-alanine or other auxiliary materials (if present) is weighed, added into water and stirred to dissolve, then the prescribed amount of oritavancin is weighed, and the oritavancin aqueous pharmaceutical solution is obtained by stirring and dissolving.
9. Use of the aqueous pharmaceutical solution according to any one of claims 1-7 for the preparation of oral liquids, injections, eye drops, topical gels, topical emulsions, sprays.
10. Use of an aqueous pharmaceutical solution according to any one of claims 1-7 and 9 for the preparation of a medicament for the treatment of a bacterial infection.
11. The use according to claim 10, wherein the bacterial infection comprises Pseudomonas aeruginosa (Pseudomonas aeruginosa), pseudomonas fluorescens (Pseudomonas fluorescens), pseudomonas acidovorans (Pseudomonas acidovorans), pseudomonas alcaligenes (Pseudomonas alcaligenes), pseudomonas putida (Pseudomonas putida), pseudomonas maltophilia (Stenotrophomonas maltophilia), burkholderia cepacia (Burkholderia cepacia), aeromonas hydrophila (Aeromonas hydrophilia), escherichia coli (Escherichia coli), citrobacter freundii (Citrobacter freundii), salmonella typhimurium (Salmonella typhimurium), salmonella typhi (Salmonella typhi), salmonella paratyphi (Salmonella paratyphi), salmonella enteritidis, shigella dysenteriae (Shigella dysenteriae), shigella flexneri (Shigella flexneri) Shigella sonnei (Shigella sonnei), enterobacter cloacae (Enterobacter cloacae), enterobacter aerogenes (Enterobacter aerogenes), klebsiella pneumoniae (Klebsiella pneumoniae), klebsiella oxytoca (Klebsiella oxytoc), serratia marcescens (Serratia marcescens), franciscensis tularensis (Francisella tularensis), morganella morganii (Morganella morganii), proteusmirabilis (Proteus mirabilis), proteus vulgaris (Proteus vulgaris), providencia alcalifasens (providencia), providencia rex (Providencia rettgeri), providencia sii (Providencia stuartii), acinetobacter baumannii (Acinetobacter baumannii), acinetobacter calcoaceticus (Acinetobacter calcoaceticus), acinetobacter (Acinetobacter haemolyticus) haemolyticus (Acinetobacter haemolyticus), yersinia enterocolitica (Yersinia enterocolitica), yersinia pestis (Yersinia pestis), yersinia pseudotuberculosis (Yersinia pseudotuberculosis), yersinia intermedia (Yersinia pestis), bordetella pertussis (Bordetella pertussis), bordetella parapertussis (Bordetella parapertussis), bordetella bronchiseptica (Bordetella bronchiseptica), haemophilus influenzae (Haemophilus influenzae), haemophilus parainfluenzae (Haemophilus parainfluenzae), haemophilus haemolyticus (Haemophilus haemolyticus), haemophilus parahaemolyticus (haemal haemophilus parasuis) (Haemophilus ducreyi), pasteuresis (Pasteurella multocida), pasteurella haemolytica (Pasteurella haemolytica), bulborococcus mucositis (Branhamella catarrhalis), helicobacter pylori (Helicobacter pylori), campylobacter feti (Campylobacter fetus), campylobacter jejuni (673), campylobacter coli (Campylobacter coli), borrelia bordetella (Borrelia burgdorferi), haemophilus cholerae (Bordetella bronchiseptica), haemophilus influenzae (Haemophilus influenzae), haemophilus parahaemolyticus (Neisseria meningitidis), vibrio vulus (35, moraxella (35) and morbus (Levalacia) are described in the genus Leideae (Leideae), legionella (35) and the genus Legionella (Legionella) such as Legionella (Legionella), legionella (35) and the genus Legionella (Legionella), the Bacteroides 3452A homolog group (Bactoides 3452A homolog group), bacteroides vulgaris (Bacteroides vulgatus), bacteroides ovatus (Bacteroides ovalus), bacteroides thetaiotaomicron (Bacteroides thetaiotaomicron), bacteroides simplex (Bacteroides uniformis), bacteroides (Bacteroides eggerthii), bacteroides viscus (Bacteroides splanchnicus), clostridium difficile (Clostridium difficile), mycobacterium tuberculosis (Mycobacterium tuberculosis), mycobacterium avium (Mycobacterium avium), mycobacterium intracellulare (Mycobacterium intracellulare), mycobacterium leprae (Mycobacterium leprae), corynebacterium diphtheriae (Corynebacterium diphtheriae), corynebacterium ulcerans (Corynebacterium ulcerans), streptococcus pneumoniae (Streptococcus pneumoniae), streptococcus agalactis (Streptococcus agalactiae), streptococcus pyogenes (Streptococcus pyogenes), streptococcus intermedius (Streptococcus intermedius), streptococcus intermedius (Streptococcus intermedius), streptococcus constellation (Streptococcus constellatus), streptococcus dysgalactiae (Streptococcus dysgalactiae), streptococcus dysenteriae (Streptomyces dysenteriae), enterococcus (Streptococcus dysgalactiae), enterococcus (enterococcus faecium faecalis), enterococcus (enterococcus) bacteria (Streptococcus dysgalactiae), enterococcus (enterococcus faecium), enterococcus (Streptococcus dysgalactiae), and enterococcus (37) vancomamoxico (37) and enterococcus (37-37), vancomycin moderately tolerating Staphylococcus aureus (vancomycin-intermediate Staphylococcus aureus), vancomycin heterogeneously moderately tolerating Staphylococcus aureus (vancomycin hetero-intermediate Staphylococcus aureus), staphylococcus epidermidis (Staphylococcus epidermidis), staphylococcus saprophyticus (Staphylococcus saprophyticus), staphylococcus intermedia (Staphylococcus intermedius), staphylococcus suis subsp. Hyicus, staphylococcus hemolyticus (Staphylococcus haemolyticus), staphylococcus hominis (Staphylococcus hominis), or Staphylococcus saccharolyticus (Staphylococcus saccharolyticus), and combinations thereof.
CN202210981782.6A 2022-08-16 2022-08-16 Stable orlistat medicine water solution and preparation method thereof Pending CN117618338A (en)

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