CN1009054B - Prepno of primycin salts - Google Patents
Prepno of primycin saltsInfo
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- CN1009054B CN1009054B CN 85105864 CN85105864A CN1009054B CN 1009054 B CN1009054 B CN 1009054B CN 85105864 CN85105864 CN 85105864 CN 85105864 A CN85105864 A CN 85105864A CN 1009054 B CN1009054 B CN 1009054B
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- acid
- primycin
- salt
- carbon atom
- barium
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Abstract
The present invention relates to Primycin salt prepared from organic acid (preferable C-[1]-16 aliphatic carboxylic acid, halogenated carboxylic acid, aliphatic dicarboxylic acid, and aromatic carboxylic acid to replace aromatic carboxylic acid or organic sulfonic acid) or inorganic acid (preferable halogen acid). The present invention further provides a process for preparing new Primycin salt, which is characterized in that suspensions of the Primycin salt prepared from aliphatic alcohols containing one to four carbon atoms and barium salt are reacted with barium salt. The sulfate of the new Primycin of the present invention has preferable antibacterial performance.
Description
What the present invention relates to is primycin (Primycin) salt, their preparation technology and the pharmaceutical preparation that comprises primycin salt.
Primycin is a kind of macrolide antibiotic (Nature174,1105/1954).The strain of Streptothrix class primycin fungus prepares primycin and they were narrated in Hungary (Hungarian) patent No.146332 with the isolated in form of sulfate with cultivating.The improvement of manufacture process adds patent No.151 in addition in Hungary (Hungarian), narrates in 197.According to Hungary (Hungarian) patent No.153,593, fermentation is to adopt the galerensis fungus strain of the mould genus of an overabundant heat spore to realize.Hungarian patent No.179,148 what relate to is a kind of remodeling of process for making, stated the segregation process of primycin sulfate there, that is: stated with alkali treatment sulfate to dissociate basic group and with above-mentioned basic group and the salifiable preparation process of mineral acid shape except that sulphuric acid.
But, the meticulous research with sensitive thin layer chromatography (being referred to as TLC later on) at present shows, the alkali treatment of primycin sulfate causes the change of primycin fine structure, and the fine structure of the preparation salt that obtains from this basic group thus is not exclusively the same with the starting substance structure.
The purpose of this invention is to provide a kind of primycin salt with fine structure the same with the fine structure of primycin antibiotics.
Further purpose of the present invention provides a kind of new salify technology, this technology can be applicable at an easy rate that plant-scale primycin sulfate directly forms various primycin salt, eliminate the technology of alkali treatment primycin sulfate thus, thereby original fine structure of primycin and antibacterial activity are remained unchanged, and need not revise technical process.
The present invention is based on such understanding: do not need to add alkali owing to adopted barium salt, the salt of various primycins directly to be obtained by primycin sulfate.The barium sulfate that forms can easily be removed from reactant mixture with Filtration, therefore can prepare various primycin salt with highly purified form with a kind of quite simple method.
Characteristics according to an aspect of the present invention, the primycin salt that provides is that (proper is that the carbon atom number is 1～16 aliphatic carboxylic acid by organic acid, halogenated carboxylic acid, aliphatic dicarboxylic acid, aromatic carboxylic acid or organic sulfonic acid) or mineral acid (proper is halogen acids) formation.
Representative preferably by primycin salt of the present invention is following salt: primycin formates, primycin acetate, primycin-chloracetate, the primycin Trichloroacetate, the primycin propionate, primycin palmate, primycin oxalates, the primycin perchlorate, the primycin bromide, primycin iodide, primycin benzoate, the primycin metilsulfate, the primycin toluene fulfonate.
By further characteristics of the present invention is to provide a kind of technology for preparing novel primycin salt, it is characterized in that: react with the aliphatic alcohol class formed primycin sulfate suspension and the barium salt that contain 1～4 carbon atom.
Barium salt can be prepared by means of suitable salt-forming reaction agent by brium carbonate or barium hydroxide.Can adopt any organic acid or mineral acid as the salt-forming reaction agent, they formed water soluble and (or) barium salt of organic solvent (particularly at the alcohols that contains 1～4 carbon atom).The salt-forming reaction agent can be an organic acid, and the aliphatic carboxylic acid that proper is contains 1～16 carbon atom (as formic acid, acetic acid, hexadecylic acid), halogenated aliphatic carboxylic acid (as trichloroacetic acid, monochloroacetic acid etc.), aliphatic dicarboxylic acid (as oxalic acid), aromatic carboxylic acid's (as benzoic acid), the aromatic carboxylic acid of replacement (as picric acid), aromatic sulfonic acid is (as the P-toluenesulfonic acid, as contain hydracid (halogen acids for example methanesulfonic acid), or mineral acid,, resemble hydrogen bromide, hydrogen iodide or perchloric acid).Can use freshly prepared barium salt.Its method is: brium carbonate is dissolved in the salt-forming reaction agent, or brium carbonate is dissolved in the alcohols (particularly methanol) that contains 1～4 carbon atom, add the salt-forming reaction agent then, the solution that obtains of evaporation in a vacuum, and in ether or in the aliphatic alcohol that contains 1～4 carbon atom (particularly methanol) dissolved residue.Plant method according to other, barium salt can be prepared by barium hydroxide, there the saturated aqueous solution of barium hydroxide and salt-forming reaction agent solution and contain 1～4 carbon atom aliphatic alcohol class (particularly methanol) and (or) water reacts, then sedimentary barium salt removed from system with Filtration.
By technology of the present invention, reasonable process is to react with primycin sulfate and the suspension and the corresponding barium salt (preferably boiling point of solvent) between 20 °～80 ℃ that contain 1～4 carbon atom aliphatic alcohol class (preferably methanol), and removes sedimentary barium salt with Filtration.It is proper reacting on the boiling point of reactant mixture, because reaction mixture has been realized completely reaction on the one hand, has improved the precipitation of barium sulfate of the form of easier solution on the other hand, therefore removes the barium sulfate ratio and is easier to realize.Barium sulfate can be removed with the method for filtering heat mixture, and proper is by a suitable filtration adjuvant, particularly adopts the Celite auxiliary agent.Filtrate is evaporated in a vacuum, and residual solids is handled with ether, filter, with ether and (or) be that 2: 1 mixed liquor washes with the ratio of acetic acid and water, drying then.So obtained the various primycin salt of powder-product form.
The novel primycin salt that obtains by the present invention demonstrates solubility preferably than known primycin sulfate up till now, has therefore caused the improvement of the situation that absorbs.
The antibacterial activity of new primycin salt of the present invention is carrying out overtesting on Gram-positive and the gram negative bacteria He on the budding fungus.The microorganism of test is listed in the table I.
These tests show that primycin salt pair gram-positive bacterium has remarkable effectiveness, to gram negative bacteria and relatively low to the effect of budding fungus.
In the test, Difco-meat soup nourishes base and is used for antibacterial, and Saab Luo Shi nourishes base and is used for fungus.5 * 10
5～5 * 10
6In the cells/ml concentration, in 37 ℃ of temperature, cultivate and carried out 24 hours.Represent with μ g/ml with the minimum inhibitory concentration value (MIC) that serial dilution is determined.
Concentration be the feed liquid of 1000 μ g/ml with butanols, the second alcohol and water is 1: 1: 2 ratio preparation.The above-mentioned feed liquid of dilute with water, its MIC value is summarized in the table II.
Adopted following primycin salt
I primycin acetate
II primycin formates
III primycin propionate
IV primycin Trichloroacetate
V primycin perchlorate
VI primycin oxalates
VII primycin palmate
VIII primycin tosilate
IX primycin benzoate
X primycin iodide
XI primycin bromide
The table I
The bacterial strain name is as follows:
1. staphylococcus aureus CCM. 885
（Staphylococcus aureus）
2. staphylococcus aureus DSM. 20231
（Staphylococcus aureus）
3. staphylococcus aureus CCM. 2317
（Staphylococcus aureus）
4. staphylococcus aureus CCM. 2326
（Staphylococcus aureus）
5. staphylococcus aureus CCM. 2514
（Staphylococcus aureus）
6. staphylococcus aureus CCM. 2515
（Staphylococcus aureus）
7. staphylococcus epidermidis CCM. 2271
（Staphylococcus epidermidis）
8.Smith staphylococcus aureus
（Staphylococcus aureusSmith）
9. feces streptococcus CCM. 1875
（Streptococcus faeealis）
10. streptococcus agalactiae CCM. 5153
（Streptococcus agalactiae）
11. streptococcus agalactiae CCM. 5534
（Streptococcus agalactiae）
12. dysgalactia streptococcus CCM. 5548
（Streptococcus disgalactiae）
13. bacillus subtilis ATCC. 6633
（Bacillus subtilis）
14. cereus bacillus CCM. 2010
（Bacillus cereus）
15. lichens bacillus CCM. 2182
（Bacillus licheniformis）
16. lichens bacillus CCM. 2205
（Bacillus licheniformis）
17. bacillus subtilis CCM. 1718
（Bacillus subtilis）
18. monokaryon Listeria monocytogenes CCM. 5576
（Listeria monocytogenes）
19. micrococcus flavus ATCC. 10240
（Micrococcus flavus）
20. brown micrococcus luteus DSM. 20030
（Micrococcus luteus）
21. urea spore sarcina DSM.317
（Sporosarcine ureae）
22. bacillus pyocyaneus CCM. 1960
（Pseudomonas aeruginosa）
23. proteus vulgaris CCM. 1799
（Proteus vulgaris）
24. bacillus ceylonensis A CCM. 1373
（Shigella sonnei）
25. Salmonella typhimurium CCM. 5445
（Salmonella typhimurium）
26. beer yeast mushroom OKI. 1282
（Saccharomyces cerevisiae）
27. pure white mycocandida CBS. 562
（Candida albicans）
28. candida tropicalis belongs to CBS. 433
（Candida tropicalis）
Provided medicine preparation by further feature of the present invention with antibiosis, comprising: the primycin salt that mineral acid or organic acid are formed (except forms by sulphuric acid salt) as effective ingredient, and select one or more other antimicrobial compositions of use and suitable inert pharmaceutical carrier, filler and (or) adjuvant mixes mutually.
That primycin salt of the present invention can be made is solid-state (as tablet, capsule, the pill of belt leather, sugar coated tablet is fastened agent), the form of semisolid (as ointment, gel) or liquid state (as injection, suspension or syrup).Proper ingredients form is a gel, surgery powder, injection or suspension and powder ampoule-solvent ampoule.
Ingredient of the present invention is suitable for oral, parenteral or rectally, or local use (as ointment).The said medicine preparation can contain commonly used and traditional pharmaceutical carrier (as magnesium carbonate, magnesium stearate, starch, Talcum, water etc.), or as the cyclodextrin and the selectable auxilliary agent (as splitting Jie's agent, emulsifying agent etc.) that adds of more effective composition.
The preparation that is suitable for oral administration can be a tablet, capsule, and belt leather pill or coated tablet, the preparation that contains primycin salt also can be used for veterinary treatment, for example is added in the feedstuff as solution.Parenteral can be aqueous emulsion, solution or suspension with preparation.The preparation that is suitable for topical application can be a powder, ointment, aqueous emulsion or fat liquor or with these solution or suspension or spray impregnated binder or wrapper material.
By further characteristics of the present invention is that preparation for pharmaceutical preparation provides a kind of technology, comprising the other antimicrobial medicament of: primycin salt that organic acid or mineral acid are formed (except forms by sulphuric acid salt) and selection as effective ingredient and suitable inert pharmaceutical carrier, filler with (or) adjuvant mixes mutually.
More detailed description of the present invention will find in the example of following indefiniteness.Unless otherwise mentioned, the mixed solvent that adopts in the example all is to represent with the ratio of volume/volume.
Example 1:
0.088 gram (0.446 mM) brium carbonate is heated to boiling in 5 milliliters of formic acid, till obtaining transparent solution.Colourless solution is evaporated in a vacuum up to drying.Residue is dissolved in 10 ml methanol, and the solution that obtains like this is added in the suspension of being made up of 1.0 gram (0.887 mM) primycin sulfate and 70 ml methanol.Reaction mixture ebuillition of heated 10 minutes under constantly stirring.Sedimentary neobalgin filters the adjuvant heat filtering through Celite.Remaining filtrate is evaporated in a vacuum, and residue is handled with ether.The white powder product is 20 milliliters of flushings of mixed liquor of 2: 1 with the ratio of acetone and water, washes with absolute ether then.So obtain 0.96 gram primycin formates, the response rate is 94.8%.MP：162～164℃，（α）
25 D＝+31.9°。(in the ratio of n-butanols, first alcohol and water is 2: 2: 1 mixed liquor, c=0.1%)
Example 2
0.88 the Carbon Dioxide barium of gram (4.459 mM) stirs in 10 milliliters of acetic acid of 100 ℃, till solid dissolves fully.Remove in a vacuum and desolvate.Residue is dissolved in 20 ml methanol, then this solution is poured into 600 ml methanol and 10g(8.87 mM) the suspension that forms of primycin sulfate in.The continuous agitating heating boiling of suspension 10 minutes.Sedimentary barium sulfate filters adjuvant through Celite and filters, and filtrate is evaporated in a vacuum.Residue is 50 milliliters of processing of mixed liquor of 2: 1 with the ratio of acetone and water, and filters.The solid that obtains is dry under infrared lamp.So can obtain 9.4 gram primycin acetate, the response rate is 91.43%.
MP：186～188℃，（α）
25 D＝+30°。
Example 3:
0.088 the trichloroacetic acid of the Carbon Dioxide barium of gram (0.446 mM) and 0.146 gram (0.887 mM) heats in 20 ml methanol, till whole brium carbonate dissolvings.The colourless solution of heat is added in the suspension of being made up of 1 gram (0.887 mM) primycin sulfate and 80 ml methanol.With reaction mixture ebuillition of heated 20 minutes.With sedimentary barium sulfate heat filtering and evaporated filtrate in a vacuum.Solid residue is handled with ether, drying, and powder-product is 15 milliliters of flushings of mixed liquor of 2: 1 with the ratio of acetone and water.So can obtain 0.96 gram primycin Trichloroacetate, the response rate 85.9%.
MP：165～166℃，（α）
25 D＝+17.9°。
Example 4:
0.088 the brium carbonate of gram (0.446 mM) stirs in 100 ℃ of 5 milliliters of propanoic acid, till whole brium carbonate dissolvings.Colourless solution evaporates in a vacuum.Residue is dissolved in 10 ml methanol, then this solution is poured in the suspension that is formed by 1.0 gram (0.887 mM) primycin sulfate and 60 ml methanol.With the continuous agitating heating boiling of suspension 10 minutes.Sedimentary barium sulfate filters adjuvant through Celite and carries out heat filtering.The filtrate that obtains is evaporated in a vacuum.Residue is that 2: 1 mixed liquor is handled and filtered for 20 milliliters with the ratio of acetone and water.So the cream-coloured primycin propionate of 0.95 gram can obtain the response rate 91.3%.MP：170℃，（α）
25 D＝+36.9°。
Example 5:
0.22 the hexadecylic acid of gram (0.887 mM) is dissolved in 15 ml methanol, then water is added in this solution, till its amount of water has not just precipitated hexadecylic acid.2.25 milliliters saturated barium hydroxide solution is added in the solution of acquisition.Sedimentary barium salt after filtering and be added in the primycin sulfate and suspension that 120 ml methanol form by 1.0 grams (0.887 mM).With reaction mixture ebuillition of heated 1 hour, hexadecylic acid barium dissolved and insoluble barium sulfate has precipitated thus.The reaction mixture of heat filters through the Celite auxiliary agent.Filtrate is evaporated in a vacuum.Residue is handled with ether and is filtered once more.The solid that obtains is 2: 1 mixed liquor flushing with the ratio of acetone and water in filter, and be dried to weight constant till.So can obtain 0.98 gram primycin, 16 salt, the response rate 82.2%.
MP：180～181℃，（α）
25 D＝+30。
Example 6:
0.087 the brium carbonate of gram (0.444 mM) is suspended in 15 milliliters the methanol, adds the oxalic acid of 0.04 gram (0.444 mM) then.The suspension ebuillition of heated that obtains like this till all dissolving, all solids (is needed 10 minutes) approximately.Remove in a vacuum and desolvate.Residue is added in 1.0 gram (0.887 mM) primycin sulfate and the 80 ml methanol solution, and with the continuous agitating heating boiling of reactant mixture 20 minutes.With sedimentary barium sulfate through Celite auxiliary agent heat filtering.Filtrate is evaporated in a vacuum.The solid residue that obtains is handled with ether, and filters.Solid in filter is 2: 1 mixed liquor flushing with the ratio of acetone and water.So can obtain the white primycin oxalates of 0.93 gram, the response rate 92.2%, MP.:186～187 ℃, (α)
25 D=+40 °.
Example 7:
0.087 the brium carbonate of gram (0.444 mM) is dissolved in the perchloric acid solution of 8.87 milliliters of 0.1N concentration, the heat back is removed in vacuum and is anhydrated a little.Residue placed 10 ml methanol and then be added to by the primycin sulfate of 1.0 grams (0.887 mM) and the suspension that 80 ml methanol form.The continuous agitating heating boiling of reaction mixture 20 minutes.The high villaumite of the primycin of Xing Chenging stays that barium sulfate then precipitates in the solution like this.The solution of heat filters through the Celite auxiliary agent, and solid matter in filter is 10 milliliters of thoroughly cleanings of mixed liquor of 2: 1 with the ratio of acetone and water.So can obtain 0.94 gram white primycin high villaumite, the response rate is 88.7%, MP.:170～171 ℃, (α)
25 D=+20 °.
Example 8:
0.087 the barium phosphate of gram (0.444 mM) is dissolved in 1 milliliter 48% the hydrogen bromide under the condition of heat a little.In a vacuum except that desolvating and grinding residue with ether.Barium bromide filtered and with dichloromethane rinse up to removing whole bromine traces.Xanchromatic barium bromide becomes oldlace.This salt is dissolved in 10 ml methanol, and the solution that obtains is added in the solution of 1.0 gram primycin sulfate of (0.887 mM) and 80 ml methanol.The continuous agitating heating boiling of the suspension that obtains like this 20 minutes.Evaporate in a vacuum with sedimentary barium sulfate filtration and with filtrate.Residue is handled and is filtered with ether.Solid matter at first is 10 milliliters of flushings of mixed liquor of 2: 1 with the ratio of acetone and water in filter, and then with 10 milliliters dichloromethane rinse.So can obtain 0.91 grammeter color primycin bromide, the response rate 87.2%.MP.：138℃，（α）
25 D＝-20°。
Example 9:
0.087 the brium carbonate of gram (0.444 mM) is dissolved under the situation of heat a little in 1.5 milliliter 57% the hydrogen iodide of methanolizing.Remove in a vacuum and desolvate.Residue is handled with ether and with 30 milliliters dichloromethane cleaning down.The yellow barium iodide that is so obtained is dissolved in 15 ml methanol, then solution is added to by in the primycin sulfate of 1.0 grams (0.887 mM) and the suspension that 80 ml methanol form.For the primycin iodide that will form are dissolved in the solution fully, with the continuous agitating heating boiling of suspension 20 minutes.The reaction mixture of heat also filters through the Celite auxiliary agent.Filtrate is evaporated in a vacuum.Residue is handled and is filtered with ether.The product that obtains is that 2: 1 mixed liquor is flushed to for 10 milliliters and does not have iodine with the ratio of acetone and water in filter, and then uses dichloromethane rinse.So can obtain the yellow primycin iodide of 0.93 gram, the response rate 85.7%.MP.：178℃，（α）
25 D＝+10°。
Example 10:
The brium carbonate of 0.087 gram (0.444 mM) is suspended in 15 milliliters the methanol, adds the benzoic acid of 0.11 gram (0.91 mM) then.The suspension that so obtains is heated to boiling, up to obtaining transparent solution.Transparent colourless solution is added to by seething with excitement 20 minutes in the primycin sulfate of 1.0 grams (0.887 mM) and the suspension that 80 ml methanol form and with the reactant mixture agitating heating.Be evaporated to drying in a vacuum through Celite auxiliary agent filtering heat solution and with filtrate.Residue is handled with ether, filters, and is the solid matter that 15 milliliters of flushings of mixed liquor of 2: 1 are obtained with the ratio of acetone and water in filter.So can obtain the primycin benzoate of 0.98 gram white powder form, the response rate 90.6%.MP.：17～171℃，（α）
25 D＝+36.9°。
Example 11:
0.088 the gram (0.446 mM) brium carbonate and 0.169 the gram (0.892 mM)-hydration p-toluenesulfonic acid in 20 ml methanol ebuillition of heated till total material enters solution.The colourless hot solution of so obtaining is poured in the primycin sulfate and suspension that 80 ml methanol form by 1.0 grams (0.887 mM).Reaction mixture constantly stirred and ebuillition of heated 20 minutes.Filter hot mixed liquor by the Celite auxiliary agent.Filtrate is evaporated in a vacuum.The ratio that residue is suspended in acetone and water is in 2: 1 the mixed liquor, filters and with above-mentioned solvent liquid cleaning.So can obtain the toluene fulfonate of the white primycin of 1.05 grams, the response rate 93.3%.Salt decomposes when heating, (α)
25 D=-3.9 °.
Example 12:
0.088 the monochloroacetic acid of the brium carbonate of gram (0.446 mM) and 0.21 gram (2.23 mM) through heating for dissolving in the ratio of 10 ml methanol and water is 1: 1 mixed liquor.Still the solution of heat is added in the primycin sulfate and suspension that 70 ml methanol form by 1.0 grams (0.887 mM).Reaction mixture was through continuous agitating heating boiling 10 minutes, and sedimentary barium sulfate filters through the Celite auxiliary agent.Filtrate is evaporated in a vacuum.The solid residue that obtains is handled with ether.The powder solid of white usefulness in filter is all washed three times with 10 milliliters of ether of water saturation at every turn, and it is constant to be dried to weight.So can obtain 0.97 gram primycin-chloracetate, the response rate 93.3%.
MP.：176℃，（α）
25 D＝+22.0°。
In following example, narrated the preparation method of the primycin salt that contains according to the present invention as the characteristic formula of effective ingredient:
Example 13:
The preparation of powder
Become dosis refracta, gram
Primycin salt 1.0
Cyclodextrin 9.0
Gross weight 10.0
Example 14
The preparation of powder
Become dosis refracta, gram
Primycin salt 1.0
Non-cement starch 9.0
（Amylum non mucilaginosum）
Gross weight 10.0
Example 15:
The preparation of powder
Become dosis refracta, gram
Primycin salt 1.0
Smoke heart grass oil 0.02
（Aetherolevm lavandulae）
Acidic silica gel 0.10
Magnesium stearate 0.10
Zinc oxide 0.20
Kaolin 0.50
Alkali formula magnesium carbonate 1.00
（Magnesium carbonicum hydroxidatum）
B-cyclodextrin 7.08
Gross weight 10.00
Example 16
The preparation of aerosol
Become dosis refracta, gram
Primycin salt 0.20
Isopropyl myristate 1.00
（Isopropyl myristate）
The 11/12 5050(carrier gas of fluorine Lyons) 99.80
Gross weight 100.00
Example 17
The preparation of aqueous aerosol
Become dosis refracta, gram
Primycin salt 0.5
Ethanol (volume ratio is 62.5%) 10.0
Water 39.5
Carrier gas 50.0
Gross weight 100.0
Example 18:
The preparation of moisture external dressing
Become dosis refracta, gram
Primycin salt 0.1
Polyethylene pyrrolidone 1.50
Ethanol (volume ratio is 62.5%) 48.40
Carrier gas 50.00
Gross weight 100.00
Example 19
The preparation of gel
Become dosis refracta, gram
Primycin salt 0.02
Chlorophyll 0.002
Menthol 0.2
Poly-adipic acid 0.12
Triethanolamine 0.15
The Tween20(tween) 0.15
Diisopropyl adipic acid fat 0.50
Ethanol (96%) 5.0
Distilled water is added to 10.0
Said mixture is installed in the flacon.
Example 20
The preparation of gel
Become dosis refracta, gram
Primycin salt 0.20
Lignocaine 2.00
Chlorophyll 0.005
Menthol 0.20
Carbopel 940 1.20
Triethanolamine 1.50
The Tween20(tween) 1.50
Dissident's diacid fat 5.00
Ethanol (96%) 50.00
Distilled water is added to 100.00
Said mixture is packed in the flacon.
Example 21
The preparation of ointment
Become dosis refracta, gram
Primycin salt 2.00
Liquid paraffin 33.00
White vaseline 31.00
96% ethanol 20.00
The Tween60(tween) 9.00
Lanoline 5.00
Gross weight 100.00
Said mixture is packed in flacon or the crucible.
Example 22
The preparation of eye ointment
Become dosis refracta, gram
Primycin salt 0.04
Ethanol (volume ratio is 62.5%) 0.08
Distilled water 3.16
Cera Flava 300.00
Cholesterol 25.00
Said mixture is diluted to 1000.0 grams with aseptic Oleum Ricini.
Example 23
The ointment of available water flushing
Become dosis refracta, gram
Primycin salt 2.0
Tween 60(tween) 5.0
Liquid paraffin 5.0
Cetostearyl alcohol 15.0
（Cetyl stearyl alcohol）
White vaseline 25.0
This mixture restrains with distilled water diluting to 100.0.
Example 24
The ointment of available water washing
Become dosis refracta, gram
Primycin salt 0.100
Ethanol (volume ratio is 62.5%) 2.000
Water 7.900
Stearic acid thiazolinyl Pyrusussuriensis ester 3.600
（Sorboxaethene Steavate）
Liquid paraffin 3.600
Hexadecane stearyl alcohol 10.800
White vaseline 18.000
Propyl group-to oxybenzoic acid ester 0.054
Methyl-to oxybenzoic acid ester 0.126
Ethanol (volume 96%) 2.930
The chloride 1.000 of lignocaine
This mixture is restrained with distilled water diluting to 100.0.
Example 25
The preparation of collyrium
Become dosis refracta, gram
Primycin salt 0.02
Sodium bicarbonate 18.00
The cement solvent
4 gram methylcellulose add that 3.5 gram NaCl add that distilled water arrives
510.00
Phenyl-hydrargyrum-borate (0.1%) 15.10
Said mixture restrains with distilled water diluting to 1000.0.
Example 26
The preparation of medicament for the eyes oil
Become dosis refracta, gram
Primycin salt 0.02
Ethanol (volume ratio is 62.5%) 0.40
Distilled water 1.58
Cholesterol 25.00
Said mixture is diluted to 100.0 grams with aseptic Oleum Ricini.
Example 27
The preparation of vaginal suppository
Become dosis refracta, gram
Primycin salt 0.02
Ethanol (volume ratio is 62.5%) 0.262
Gelatin 1.40
Sodium acetate 0.26
Glycerol 4.50
This mixture is diluted with water to 9.5 grams
Example 28
The preparation of soluble tablet
Become dosis refracta, gram
Primycin salt 0.4
Urea element or NaCl 9.6
Primycin salt and filler be dissolved in 60% the ethanol, evaporate this solvent and granule is pressed into tablet.
Example 29
The preparation of antimicrobial binder
Primycin salt is dissolved in the ethanol binder (as trauma dressing, the gauze) solution impregnation that obtains.The binder of handling is pressed known method packing and sterilization.The sterilization binder with antimicrobial usefulness that so obtains is applicable to any purposes.
Claims (8)
1, the preparation method of novel primycin salt, it is characterized in that reacting as the aliphatic carboxylic acid that contains 1～16 carbon atom or the halogenation aliphatic carboxylic acid that contains 1～4 carbon atom or aliphatic dicarboxylic acid that contains 2～6 carbon atoms or benzoic acid or the barium salt of organic sulfonic acid that contains the replacement of 1～7 carbon atom with primycin sulfate suspension and the organic acid of the aliphatic alcohol that contains 1～4 carbon atom, or with the barium salt reaction of the halogenide of mineral acid such as hydrogen or high hydracid, wherein mineral acid is not a sulphuric acid.
2, the method for claim 1, it is characterized in that the described aliphatic carboxylic acid that contains 1～16 carbon atom is formic acid, acetic acid, propanoic acid or hexadecylic acid, the halogenation aliphatic carboxylic acid that contains 1～4 carbon atom is trichloroacetic acid, monochloroacetic acid, the aliphatic dicarboxylic acid that contains 2～6 carbon atoms is an oxalic acid, the organic sulfonic acid that contains the replacement of 1～7 carbon atom is p-methyl benzenesulfonic acid or methanesulfonic acid, the halogenide of hydrogen is hydrogen bromide, hydrogen iodide or hydrogen chloride, and high hydracid is a perchloric acid.
3, claim 1 or 2 method is characterized in that fresh preparation barium salt.
4, the method for claim 3, the preparation that it is characterized in that barium salt is by brium carbonate or the brium carbonate solution that contains the aliphatic alcohol of 1～4 carbon atom are dissolved in corresponding organic acid or the mineral acid, the solution that evaporation obtains, and dissolved residue is freshly prepared in aliphatic alcohol that contains 1～4 carbon atom or ether.
5, the method for claim 4, the preparation that it is characterized in that barium salt is by making barium hydroxide saturated aqueous solution and the corresponding organic acid that is formed by aliphatic alcohol that contains 1～4 carbon atom and/or water or the solution reaction of mineral acid, filters mixed liquor then and freshly prepared.
6, claim 1 or 2 method, the reaction that it is characterized in that primycin sulfate and barium salt is to carry out under 20～80 ℃ temperature, is preferably under the boiling temperature of solvent.
7, the method for claim 6 is characterized in that separating formed primycin salt.
8, the method for claim 7 is characterized in that by filtering barium sulfate, and evaporated filtrate is realized described the separation with handling with solvent (The suitable solvent is that volume ratio is 2: 1 the acetone and the mixed liquor and/or the ether of water) in the vacuum.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 85105864 CN1009054B (en) | 1984-07-03 | 1985-08-02 | Prepno of primycin salts |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU842571A HU196822B (en) | 1984-07-03 | 1984-07-03 | Process for producing primicin salts |
| CN 85105864 CN1009054B (en) | 1984-07-03 | 1985-08-02 | Prepno of primycin salts |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN85105864A CN85105864A (en) | 1987-01-28 |
| CN1009054B true CN1009054B (en) | 1990-08-08 |
Family
ID=25741923
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 85105864 Expired CN1009054B (en) | 1984-07-03 | 1985-08-02 | Prepno of primycin salts |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1009054B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1050563C (en) * | 1993-09-02 | 2000-03-22 | 维尔内和普弗雷德尔公司 | Screw element for a screw-type extrusion machine |
-
1985
- 1985-08-02 CN CN 85105864 patent/CN1009054B/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1050563C (en) * | 1993-09-02 | 2000-03-22 | 维尔内和普弗雷德尔公司 | Screw element for a screw-type extrusion machine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN85105864A (en) | 1987-01-28 |
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