US 3072531 A
Description (OCR text may contain errors)
Jan. 8, 1-963 v w. o. GODTFREDSEN ETAL 3,072,531
ANTIBIOTIC AND THERAPEUTIC COMPOSITIONS; THEREOF Filed Sept. 12, 1961 WAVE NUMBER CM WAVE LENGTH IN MICRONS IWENTORS N WA 6N at E 600 TFREDSEN HEN/VINE OTTO BOJSEN LORCK SVERR-E J HIVSE'N I ATTORNEYS United States Patent This invention relates to a new and useful acidic antibiotic called Antibiotic ZN6, to its production by fermentation under controlled conditions of the fungus Fusi dium coccineum (K. Tubaki), to methods for its recovery and concentration from crude solutions and to processes for its purification.
FIGURE 1 is an infra-red absorption spectrum which is useful in describing certain properties of Antibiotic ZN-6 according to the invention.
The present invention includes within its scope the anti biotic in dilute forms as crude concentrates, the pureantilbiotic itself and its salts with pharmaceutically acceptable inorganic and organic bases as well as pharmaceutic compositions and a dosage unit containing the same.
The organism producing the antibiotic of the present invention can be obtained from Centraal Bureau voor Schimrnelcultures, BaarmHolland registered alphabetically under the name Fusidz'um coccineum (K. Tubaki. The strain is classed with the species Fusia'ium coccincum, and a synonym of that species is Ramularia coccinea. The genus Fusidiurn belongs to the tribus Oosporeae, the family Mucedinaceae, and the order Hy- .phornycetales.
Antibiotic ZN-6 is a weak carboxylic acid capable of forming a variety of salts with inorganic and organic bases. An electrometric titration performed in 80% aqueous ethanol gave a pK -value of 7.25 corresponding to a pK -value of about 5.3 in water. Furthermore the titration studies indicate an equivalent weight of the substance amounting to 516. Investigations dealing With its chemical structure, and its analytical data, indicate that the substance has the elementary formula C H O and contains in the mole cule a cyclopentenopolyhydrophenanthrene ring system which is substituted with two hydroxy groups, one acetoxy group and vfour methyl groups, andwhich in the 17-position is connected by a double bond with the cc-carbon atom of 5-methyl-4,5-heptenoic acid.
As yet, the structural formula of Antibiotic ZN-6 has not been exactly established, but the substance is believed to have the proposed Formula I, in which the wavy connection-lines indicate that the configuration in question is uncertain.
Formula I CHz-CHz-CH=C o-oonst on: on, 3 n i g OOG.CH OHJ 3 Antibiotic ZN-6 is sparingly soluble in water and p hexane, whereas it is soluble in ethanol, acetone, methyl butyl ketone, amyl acetate, chloroform and similar solvents.
On paper chromatography using the "systems described by Bush (50 Biochemical Journal, 370 (1952)), the movements of Antibiotic ZN-6 correspond to the R,- values 0.38 and 0.73 in the B(l)- and B(5)-system respectively.
Antibiotic ZN-6 is capable of forming solvates with certain solvents. With benzene for instance it forms a crystalline solvate, which is soluble in hot benzene, but sparingly soluble in cold benzene. The benzene solvate of Antibiotic ZN-6 has a melting point of 189-1895 degrees centigrade.
After drying the said solvate at 50' degrees centigrade and an absolute pressure of 0.01 mm. Hg to constant weight, a pure product is obtained, which is free from benzene, and has the melting point of 191-192 degrees centigrade, the specific rotation [011 of minus 9 de grees in a 1% solution in chloroform, and at 220 m a molar extinction coeflicient of 8000 in ethanol and no characteristic absorption bands above this wave-length.
The pure Antibiotic ZN-6 is further characterized by its spectrum in the infra-red region as shown in FIGURE 1, from which it appears that it exhibits characteristic absorption bands at the following frequencies, expressed in reciprocal centimeters: 1265, 1385, 1695, 1730 and 3450, using for the purpose the potassium bromide technique.
According to bacteriological experiments, Antibiotic ZN-6 has proved to be effective against a number of pathogenic micro-organisms, especially Staphylococcus aureus, Ncz'sscria gonorrhoeae and their penicillin-resistant strains, N ez'sseria meningitides,Mycobacterium tuberculosis and the streptomycim, isonicotinic acid hydrazideor p-arninosalicylic acid-resistant strains of the same organism, and Corynebacterium diphtheriae.
The more specific antifungal and antibacterial activity of the antibiotic of the invention can be notedfrom the following Table I in which the activity is expressed as the amount of the Antibiotic ZN-6 Na-salt in mgs. per liter which causes 50% inhibition of the organism in ques tion after the period of time (in hours) indicated:
TABLE I Organism Substrate Time Activity Staphylococcus aureus Staphylococcus aurcus, penicillinaseproducing strain.
Staphylococcus aurcus, penicillin-resistant laboratory strain producing no penicillinase.
Neisscrza gouorrhoeac Blood-ascites 4 agar.
Neisscria gouorrhocae, penicillino resistant strain.
Ncisscria Haemophllus influenzac Diplococcus pncumom'uc rin Bouillon with Streptococcus pyogenes Streptococcus (oocpidcmicus Streptococcus Streptococcus lactis Streptococcus faecalis Pseudomouas aerugino Vibrio comma Alcalioencs faecal'is Escherichia coli Klebsiella pneumoniae Scrralia mar Proteus vulguris Salmonella lr/phimurium Bacillus sublilis Mycobacterium tuberculosis var. from- Mycobactcrium tuberculosis var. hom.
streptomycin-resistant strain. Mycobacterium tuberculosis var. hom.
strain resistant to pamino-salicylic acid. Mycobacterium tuberculosis var. hom. strain resistant to isonicotinic acid hydrazide.
TABLE I--Continued Clinical tests carried out in connection with the present invention have demonstrated that Antibiotic ZN6 and certainof its salts meet the requirements for pharmaceutically acceptable antibiotics, since they are usable in the treatment of infectious diseases, and particularly valuable in the treatment of those which are produced by various strains of Staphylococci, including the penicillinresistant strains.
For pharmaceutical purposes, Antibiotic ZN6 may be used as such or in the form of its more or less watersoluble salts with atoxic inorganic or organic bases.
Although aqueous solutions of Antibiotic ZN6 salts can be administered parenterally, the salts are preferably given by mouth, since they pass readily from the gastrointestinal tract to the body-fluids, in which an adequate concentration of the antibiotic is demonstrable for a satisfactory period of time.
This has been established in a resorption test in which 8 persons were individually given by mouth a single treatment consisting of two capsules each containing 0.250-gram of the sodium salt of Antibiotic ZN6, whereupon the plasma-concentrations were determined at fixed intervals afterthe intake. The results obtained are given in Table II in which the figures indicate the said plasmaconcentration expressed in p-gms. per ml. plasma one or 'more hours after the intake.
rn'omu I the persons were given the drug on an empty stomach, whereas the persons of Group II were given the drug after a meal.
In a similar test, the average plasma-concentration found 24 hours after the intake of the same amount of the drug amounted to 0.75 ,u-gms. per ml., indicating the extremely slow-elimination of the substance from the body.
A suflicientlow acute toxicity of Antibiotic ZN6 has "been observed 'in animal experiments in which the test animals were mice. The following'values of LD expressed in mgs.jper kilo body weight were found: (a) The sodium salt of Antibiotic ZN-6 administered intravenously 200-250 '(b) The sodium salt of Antibiotic ZN6 administered subcutaneously' 400 (c) The benzene solvate of Antibiotic ZN6 administered perorally; 1500 -Fur-thermore,'in prolonged toxicological experiments,
in which the animals, male and female rats, were treated .orally six days out of each week with the Antibiotic ZN6 sodium salt in doses of 0.400 gram per kilo of body weight, neither significant differences in weight between .the test animals and control animals nor any pathological changes caused by the drug were observed, indicating the absence of chronic toxicity.
The unique properties of Antibiotic ZN6 have been demonstrated to a more striking extent by controlled clinical use of the Antibiotic ZN6 sodium salt in the form of a suitable composition incapsulated in gelatine capsules on patients suffering from furunculosis, osteomyelitis and endocarditis.
After oral treatment of the patients at daily or like intervals convenient for practical use and for a sufficient period of time, the cures were almost 100% without the occurrence of secondary effects or toxic reactions, and no relapses were observed even after prolonged observations.
For clinical treatments, the water-soluble salts of Antibiotic ZN-6, and particularly the sodium salt, is applicable.
On the other hand, slightly water-soluble salts of Antibiotic ZN-6 or even the free acid, can also be used for oral administration, whereby the absorption rate of the drug may decrease, so that it preferably exerts its activity in the gastro-intestinal tract itself, which may be desirable in the treatment of certain diseases.
Besides, the slightly water-soluble salts of Antibiotic ZN6 may be injected in the form of a suspension of the salt in a suitable medium in order to produce even longer blood levels of the antibiotic than described before.
In the method of the invention the fungus Fusidium coccineum (K. Tubaki) is grown under aerobic conditions in a fermentation medium containing carbohydrates, nitrogen sources, e.g. complex organic materials such as proteins, and suitable amounts of the inorganic salts and other substances necessary for the nutrition of the fungus, and the fermentation is continued until a substantially antibiotic activity has been imparted to the said solution, after which the Antibiotic ZN6 thus produced is recovered, concentrated and isolated in pure form or is converted to one of its salts with pharmaceutically acceptable bases by way of known reactions.
When performing the method of the invention, the production rate of Antibiotic ZN6 is determined throughout the fermentation by routine evaluation of the activity of culture filtrated, for which purpose the agar-plate assay may be employed, using for instance Staphylococcus aureus as the test organism.
According to results obtained from the production of Antibiotic ZN6 on a technical scale, the optimum yield of the substance was obtained in the course of -100 hours when the process of fermentation was performed between 20 and 30 degrees centigrade, and preferably between 24 and 28 degrees centigrade. The time in usual practice is 2 to 7 days.
However, the said ranges are not limitating to the invention, since the period of time required for obtaining the said yields depends to some degree on the mechanical design of the fermentation vessel and the type of agitator used.
In this connection it should be mentioned that the vessels employed were commercial size units containing from 10 to 30 cm. of the culture medium and not specifically designed for the production of Antibiotic ZN-6.
A variety of the well known culture media have proved usable as culture media for carrying out the method, although those containing as the protein source corn steep liquor or soy bean meal, and as the carbohydrate source glucose or saccharose are preferred. Among other constituents of an adequate culture medium may for instance be mentioned yeast extract, ,glycerine, maltose, fructose, fatty acids, casein hydrolysate, aminoacids and water-soluble vitamins.
When the production of Antibiotic ZN6 in the fermentation process ceases, or when a satisfactory yield has been obtained, the antibiotic substance can be recovered by a variety of procedures.
Advantageously, the first stepto recover the'substance for instance active carbon or ion-exchange resins or,
preferably, the broth is extracted with a suitable solvent or mixtures of solvents, if necessary after having adjusted the aqueous Antibiotic ZN-6-containing medium to an adequate pH-value, preferably below 7.0 and most desirably in the range between 3.0 and 6.0. As suitable solvents can be mentioned esters, ketones or halogenated hydrocarbons. In the commercial scale production however, specifically methyl isobutyl ketone, amyl acetate and butyl acetate have proved to be suitable for the extraction of the fermentation broth.
volume the organic phase from which the Antibiotic ZN-6 may be precipitated on cooling or may be precipitated by adding tothe' concentrate a component which reduces. the solubility of ZN-6, and preferably by evaporation of the organic phase to dryness and addition of benzene in order to obtain the readily crystalliz-able benzene solvate mentioned hereinbefore. I
Alternatively, the acidic properties of Antibiotic ZN-6 permit the performance of a subsequent extraction of the organic phase with an aqueous alkaline solution or with an aqueous suspension of an alkaline compound, whereby more or. less concentrated aqueous solutions of AntibioticZN- salts are obtained.
By acidification of such solutions, Antibiotic ZN-6 can be precipitated or, if desired, the salt of Antibiotic ZN6 contained therein can be isolated as such.
In an appropriate embodiment of the invention the v readily crystallizable benzene solvate is produced directly from the said aqueous solution of an Antibiotic ZN-6 salt, if necessary after having removed part of the water by evaporation, for instance in a vacuum evaporator, by adding to the aqueous concentrated solution a sufficient amount of benzene to formthe solvate, and acidifying in order to precipitate Antibiotic ZN-6 in the form of the said solvate, which after isolation and drying yields either the pure benzene solvate or Antibiotic ZN-6 itself, depending upon the conditions of drying and the temperature used, the benzene being liberated from the solvate at elevated temperatures.
With regard to the purification of Antibiotic ZN-6, its ability to form solvtates with certain solvents is an important feature. Thus for instance, in another appropriate embodiment of the invention, the crude Antibiotic ZN-6 is dissolvedin a small volume of hot methanol, from which the methanol solvate crystallizes on cooling in a surprisingly pure form, so that this method is particularly suitable for obtaining a pharmaceutically acceptable quality of the substance. The said methanol solvate has a melting point of 179-1795 degrees centigrade.
When salts of Antibiotic ZN-6 are desired, they can .be produced by simple neutralization of Antibiotic Z N6 or one of its solvates with the base in question in the presence of a suitable reaction medium facilitating the ethylamine-, piperidine-, m0rpholine-, cyclohexylamine and monoethanolamine salt, and the slightly water-soluble calcium-, magnesium-, dibenzyl-ethylene-diamine-, benzyl-fl-phenylethylamineand procaine salt. All of these have been prepared by procedures similar to those used for the preparation of the sodium solt and all have useful properties of the same character.
Among other salts which can be produced according to the method of the invention and which have similar properties may for instance be mentioned those. containing as the base-component pyrrolidine, piperazine, guanidine, methylamine, ethylamine, benzylamine orsimilar unsubstituted or substituted amines. Furthermore quaterreaction and from which the salt may precipitate or, if
necessary, can be precipitated by adding a suitable component to depress the solubility of the desired salt, or the salt can be isolated by evaporating the reaction mixture.
Alternatively, a salt of Antibiotic ZN-6 prepared in advance can be reacted withthe base inquestion, or the desired salt of Antibiotic ZN-6 can be prepared by a double decomposition of a previously prepared Antibiotic ZN-6 salt andanother salt containing the desired metal-ion or base.
Among the useful salts which have been prepared are the water-soluble sodium-, potassium-, ammonium-, trinary amines as choline and its derivatives or other antibiotics having basic properties as for instance streptomycin form salts according to the invention which have similar properties. I
The invention furthermore concerns therapeutical compositions adapted for use in the treatment of infectious diseases. The compositions of the invention contain as the therapeutically active component or components one or more members of the class consisting of Antibiotic ZN-6 and its salts with atoxic pharmaceutically acceptable bases, mixed up with solid or liquid pharmaceutical carriers and auxiliary agents. I V
In the said composition, the proportion of therapeuticallyactive material to carrier substances and-auxiliary agents can Vary between 1% and 95%.
The composition in question can either be worked up to pharmaceutical forms of presentation such as tablets, pills, dragrees and suppositories, or the composition can be filled in medical containers such as capsules or ampoules or, as far as mixtures or ointments are concerned, the may be filled in bottles or tubes and similar containers. s
Pharmaceutical organic or inorganic, solid or liquid carriers suitable for enteral, parenteral or local administration can be used to make up the composition, water, gelatine, lactose, starch, magnesium stearate, talc, vege table and animal oils and fats, benzyl alcohol, gum, polyalkylene glycol, petroleum jelly, cocoa butter, lanolin or other known carriers for medicaments are all suitable as carriers, while stabilizing agents, wetting or emulsifying agents, salts for varying the osmotic pressure or buffers for securing an adequate pH-value of the composition can be used as auxiliary agents.
The water-soluble sodium salt of Antibiotic ZN-6, which is a stable crystalline substance, is one of the preferred active constituents of the compositions of the invention. On the other hand, for therapeutic purposes requiring a special absorption rate of the drug it will in some cases be advantageous to use a composition containing both a water-soluble salt and a sparingly watersoluble salt of Antibiotic'ZN-o as active constituents, and even the free Antibiotic ZN-6 may be used as such.
As an example of a compositionaccording to the invention one may use an ointment adapted for the treatment of local infectious diseases of the skin and containing 10 mgs. of the Antibiotic ZN-6 sodium salt per gram.
This ointment is prepared according to the following.
The stearyl alcohol, white wax and white petrolaturn are melted together on a steam bath. Thereafter the cholesterol is added and dissolved in the melted mixture which is then stirred until cold. The sodium salt of Antibiotic ZN-6 is sieved through an mesh per linear inch I sieve and triturated gradually with the ointment base.
Another object of the invention resides in the selection of a dose of the Antibiotic ZN-6 and its salts which can be administered so that the desired activity is achieved without simultaneous secondary efiects'.
It has been found that Antibiotic ZN-6 and its salts are conveniently administered in dosage units containing not less than 0.05 gm. and preferably from 0.1 to 1.0 gm. in total Antibiotic ZN-6, calculated as the free acid.
By the term dosage unit is meant a unitary, i.e. a single dose capable of being administered to the patients, and which may be readily handled and packed, remaining as a physically stable unit dose comprising either the active material as such as a mixture of it with solid or liquid pharmaceutical diluents or carriers.
It the composition is to be injected, a sealed ampoule,
a vial or a similar container may be provided containing a parenterally acceptable aqueous or oily injectable solution or dispersion of the active material as a dosage unit mentioned above.
As an example of a dosage unit, the prescription below describes the preparation of suitable tablets containing each 0.250 gram of Antibiotic ZN-6 sodium salt.
The Antibiotic ZN-6 sodium salt and the lactose are screened through a 20 mesh per linear inch sieve and mixed together for minutes. Thereafter the mixed powders are wetted With a solution of polyvinylpyrrolidone in 96% ethyl alcohol. The moist mass is passed through a 10 mesh per linear inch screen and then dried at 38 degrees centigrade. When the alcohol has evaporated, the granules are broken on a 16 mesh per linear inch sieve and mixed with the corn starch, talc and magnesium stearate. The granulate is compressed into tablets of 0.50 gram weight using inch punches and dies, yielding 1000 tablets each containing 0.250 gram of the Antibiotic ZN-'6 sodium salt.
In a particular preferred form of administration, capsules are employed of, for instance gelatine or another material easily digestible or disintegrable in the intestinal tract, preferably containing 0.250 gram of the Antibiotic ZN-6 sodium salt, if necessary, mixed with minor amounts of auxiliary substances in order to obtain -a freeilowing powder fitted for the purpose of filling the capsules. Such capsules are conveniently prepared in accordance with the following description.
Ingredients: Gms. Antibiotic ZN-6 sodium salt 250 Lactose -27 Magnesium stearate 3 The ingredients are passed through a '60 mesh per linear inch sieve and mixed for 15 minutes. The mixture is filled into No. 0 gelatine capsules (Parke, Davis and C0.), using a semi-automatic capsule-filling machine shaken by vibrator. Each capsule contains 280 mgs. of the mixture corresponding to 250 'rngs. of the Antibiotic ZN-6 sodium salt.
The invention will now be illustrated by the following examples from which the details of the embodiments will be apparent.
EXAMPLE 1 The Benzene Solvate of Antibiotic ZN-6 In a 1.5 m. fermentation tank of stainless steel equipped with an agitator 1.00 m. of a culture medium of the following composition was made up:
Tap-water up to 1000 liters.
The culture medium had a pH-value of 6. 1, which value was adjusted to 6.5 by adding a dilute solution of NaOH, Whereafter the medium was sterilized by heating. After cooling it was inoculated with 3 liters of a culture of Fusidium coccineztm (K. Tubaki) grown for 48 hours in a shaking flask at 28 degrees centigrade. The contents of the tank were stirred and aerated at a rate of 0.6 m5 of air per hour at 28 degrees centigrade for 96 hours. During this period of time it was not necessary to adjust the pH in order to maintain the aforesaid value of 6.5. After the said period of fermentation the antibiotic activity of the culture medium determined by the usual agar cup test on Staphylococcus aureus was found to correspond to a content of 70 mgs. of Antibiotic ZN-6 per liter by comparing it with the activity of that substance determined by the same method.
The mycelium was separated from the culture medium by filtration, and the amount of filtrate was 700 liters. The pH of the filtrate was adjusted to 3.3 by adding a 25% solution of H and the filtrate was extracted with 230 liters of butyl acetate in counter-current in a Podbielniak extractor. The butyl acetate phase thereby obtained was extracted with one portion of 77 liters of water to which a 10% solution of NaOH was added until the pH of the aqueous phase was 10.0, whereafter the aqueous phase was separated from the butyl acetate phase. The pH of the aqueous phase was adjusted to 3.2 by adding a 25% solution of H 80 and the solution was extracted with 40 liters of methyl isobutyl ketonc. The methyl isobutyl ketone phase was separated from the aqueous phase, treated with 40 grams of active carbon, and subsequently evaporated to dryness in vacuo at a boiling temperature of 25 degrees centigrade. The residue was dissolved in 500 mls. of benzene and the solution was left standing overnight in a refrigerator. Thereby, the benzene solvate of Antibiotic ZN-6 crystallized. It was filtered off and recrystallized from benzene, yielding 12.0 grams of the pure substance with a melting point of 189189.5 degrees centigrade.
EXAMPLE 2 The Sodium Salt of Antibiotic ZN-6 I 500 mgs. of the benzene solvate produced according to Example 1 were suspended in 20 mls. of water, and to the suspension was added /2 N aqueous NaOH until the pH was 9.0. The solution was filtered, and to the filtrate 50 mls. of n butanol were added, whereafter the water content of the solution was removed by azeotropic distillation in vacuo. From the residue the desired so dium salt was precipitated byv addition of ether. It was filtered off, washed with ether and dried. By recrystallization from ethanol-acetone, 360 mgs. of the pure, crystalline sodium salt were obtained.
EXAMPLE 3 Production of Antibiotic ZN-6 Spores of Fusidium coccineum (K. Tubaki) were transferred from an agar slant to 3 liters of a sterile 9 Gms. per liter KH PO 0.6 SOy bean meal V 3.0 NaCl 4.0
PeSO .7I-I O i i 0.005 CuSO 5H O 0.004
andthe culture was aerobically incubated at 27 degrees Centigrade for 40 to 60 hours in a reciprocating shaker. The seed material thus obtained can be used directly as an inoculum for a commercial scale fermentor. case, however, it was transferred to a 700 liter vessel containing a culture medium of the same composition as that of the commercial scale fermentor, and was incubated at 26 degrees centigrade for 40-48 hours in order to achieve the development of vegetative growth of the fungus before inoculating the main fermentor.
-Subsecpiently 16 m. of a culture medium of the following composition:
which before sterilization had been adjusted to a pH- value of 7.2 was sterilized in the main fermentor at a temperature of 120 degrees centigrade for /2 hour and after cooling it was inoculated with one of the two forms of inoculation material mentioned before. While agitating and forcing in air through -a sparker at a rate of the order of 0.5 liter of air per liter of culture fluid per EXAMPLE 4 Production of Antibiotic ZN-6 16 m. of a culture medium of the following composition:
Gms. per liter Corn steep liquor, 50% 2.5 Soy bean meal or meat meal 10.0 Saccharose 30.0 Glycerine 7.5 NaC1 4.0 KH PO 0.5 0.5
which before sterilization had been adjusted to a pH of 6.80 was sterilized in the fermentor at 120 degrees centigrade for /2 hour. After cooling the medium was inoculated with the inoculum mentioned in Example 3, and the fermentation was continued for 100 hours,
In this 10 Which before sterilization had been adjusted to a pH of 6.8 was sterilized in the fermentor at 120 degrees centigrade for hour and after cooling inoculated with the inoculurn mentioned in Example 3. After fermenting for Glucose grns. per liter ,30 Glycerine do .5 KH PO 2H O do 5 NaNO do 6 KCI do 0.5 .MgSO 7H O do 0.5 ZnSO .6H O mg. per liter 1.0 Yeast extract (Difco) "gins. per liter" 0.12 a
thereby yielding an Antibiotic ZN-6 concentration in the.
culture medium amounting to 260 in -gins. according to the agar cup assay.
EXAMPLE 5 Producti n of Antibiotic ZN-6 16 m3 of a culture medium of the following composition:
Grns. per liter Saccharose -Q 60.0 Corn steep liquor, 50% 20.0 KH PO 10.0 MgSO .7H O
hours under conditions similar to those of Example 3, the yield of Antibiotic ZN-6 amounted to 250 mn-gms. per ml. of culture medium.
. EXAMPLE 6 Isolation and Purification of Antibiotic ZN-6 The clarified fermentation broth (15 m. from Example 5 (containing 3.75 kgs. of Antibiotic ZN-6 as de- 'phase was adjusted to a pH of 9.3 and evaporated in a vacuum evaporator to a volume of 150 liters containing 3.25 kgs. of Antibiotic ZN-6.
40 liters of benzene was added, and, while stirring, the pH of the aqueous phase was adjusted to 5.0 by addition of hydrochloric acid. The stirring was continued for 4 hours, after which the precipitate, consisting of Antibiotic ZN-6 benzene solvate Was filtered off, washed with water and benzene and dried. The crude product (2.8'kgs.) was dissolved in 12 liters of methylene chloride, filtered and evaporated todryness in vacuo. The residue was dissolved in 3.2 liters of hot methanol, and upon cooling to 0 degrees centigrated a methanol solvate crystallized which was filtered otli, washed with 3 x 300 mls. of ice-cold methanol and dried, yielding 2.48 kgs. of colorless methanol solvate.
This product was suspended in a mixture of 750 mls. of methanol and 1750 mls. of acetone, and after the addition of a few drops of phenolphthalein indicator, 33% aqueous sodium hydroxide was added while stirring until a faint red color developed. The resulting solution was filtered through dicalite, mixed with 5 liters of methyl isobutyl ketone and concentrated in vacuo to about 3 liters. During the concentration the sodium salt crys- It was filtered off, washed with acetone fol lowed by ether and dried to yield 2.35 kgs. of pure sodium salt.
EXAMPLE 7 Antibiotic ZN-6 Salts With Organic Bases GENERAL PROCEDURE To a solution of 517 mgsyof Antibiotic ZN-6 in 5 mls. of acetone, one millimole of the organic base followed by 2.5 mls. of hexane were added, after which the salts crystallized by scratching. They were collected and purified by recrystallization from an appropriate solvent. I
1 sparingly soluble in Water.
I EXAMPLE 8 Recovery of Antibiotic ZN-6 From the Fermentation Broth 200 mls. of the anion-exchange resin Amberlite IRA 401 S (OH) were stirred for two hours with three 2 liter portions of a clarified broth containing of Antibiotic ZN-6 per ml. During the stirring the pH was kept at 9.5 by addition of 2 N aqueous sodium hydroxide.
Analyses of the filtrates showed that 85% of the Anti biotic ZN-6 had been absorbed on the resin. After filtration the resin was Washed with three 1.5 liter portions of water and thereafter suspended in 500 ml. of acetone. While stirring the pH was lowered to 3.6 during three hours by addition of 6 N hydrochloric acid, whereafter the resin was filtered off and Washed with acetone (2 x 100 mls.).
The combined filtrate and washing contained 375 mgs. of Antibiotic ZN-6, corresponding to 57% of the amount present in the broth.
EXAMPLE 9 Recovery of Antibiotic ZN-6 From the Fermentation Broth 1 liter of a clarified broth containing 500 mgs. of Antibiotic ZN-6 was stirred for one hour with gs. of decolourizing carbon (S.E.C.A. III). After filtration, the filtrate was analyzed and found to contain less than 25 mgs. of Antibiotic ZN6. The filter-cake was washed with water and thereafter refluxed with 100 mls. of methanol for two hours, cooled and filtered. The filtrate contained about 150 mgs. of Antibiotic ZN-6.
In view of our invention and disclosure, variations and modifications to meet individual whim or particular need will doubtless become evident to others skilled in the art, to obtain all or part of the benefits of our invention without copying the process and composition shown, and we, therefore, claim all such insofar as they fallwithin the reasonable spirit and scope of our claims.
Having thus described our invention, what we claim as new and desire to secure by Letters Patent is:
1. A weakly acidic antibiotic designated Antibiotic ZN-6, that is sparingly soluble in water and hexane, and soluble in ethanol, acetone, methyl isobutyl ketone, amyl acetate and chloroform; melting at 191-192 degrees centigrade, having a specific rotation of minus 9 degrees in a 1% solution in chloroform; whose spectrum in the infra-red region, using the potassium bromide technique, exhibits characteristic absorption bands as shown on the drawing and exhibiting the values at the follow ing frequencies expressedv in reciprocal centimeters: 1265, 1385, 1695, 1730 and 3450; having at 220 m a molar extinction coeflicient of 8000 in ethanol and no characteristic absorption bands above this wave-length; having the molecular formula C H O and containing in the molecule a cyclopentenopolyhydrophenanthrene ring system which is substituted with two hydroxyl groups, one acetoxyl group and four methyl groups, and which in the 17-position is connected by a double bond with the a-carbon atom of 5-methyl-4,5-heptenoic acid; and forms antibiotically active salts with pharmaceutically acceptable inorganic and organic bases.
2. As an antibiotically active compound, the sodium salt of Antibiotic ZN-6 as defined in claim 1.
3. As an antibiotically active compound, the calcium salt of Antibiotic ZN6 as defined in claim 1.
4. As new compounds, the solvates of Antibiotic ZN-6 as defined in claim 1 with pharmaceutically acceptable solvents.
5. As a new compound, the benzene solvate of Antibiotic ZN-6 as defined in claim 1.
6. As a newcornpound, the methanol solvate of Antibiotic ZN-6 as defined in claim 1.
7. A process for producing Antibiotic ZN-6 as set forth in claim 1 containing fermentation broth, comprising cultivating the fungus Fusidium coccineum (K. Tubaki) in an aqueous nutrient-containing carbohydrate solution until substantial antibiotic activity is imparted to said solution.
8. In a process for producing Antibiotic ZN-6 as set forth in claim 1, the step of extracting with an organic solvent or mixture of solvents the Antibiotic ZN-6 from an aqueous medium containing the substance.
9. In a process for producing Antibiotic ZN6 as set forth in claim 1, the steps of adsorbing Antibiotic ZN-6 as set forth in claim 1 from an aqueous medium by intimately contacting the aqueous medium with a solid adsorbing agent, and eluting the Antibiotic ZN-6 from the solid adsorbing agent.
10. In a process for purifying Antibiotic ZN-6 as set forth in claim 1, the steps comprising dissolving in benzene the crude substance, crystallizing its benzene solvate from the solution, separating the benzene solvate thus precipitated and driving off the solvent to liberate Antibiotic ZN-G as set forth in claim 1.
11. In a process for concentration of Antibiotic ZN-6 as set forth in claim 1, the step which comprises extracting a solution of said substance in a water-immiscible solvent or mixture of solvents with an aqueous alkaline medium, thereby obtaining a concentrated aqueous solution of an Antibiotic ZN-6 salt.
12. In a process for the isolation of Antibiotic ZN-6 as set forth in claim 1 from aqueous solutions containing the same, the steps comprising adding benzene to said solution, acidifying the mixture, separating the benzene solvate of Antibiotic ZN-6 thus precipitated and producing therefrom a compound of the class consisting of Antibiotic ZN-6 as set forth in claim 1 and a salt thereof.
13. In a process for producing pure salts of Antibiotic ZN-6 as set forth in claim 1, the steps comprising crystallizing its methanol solvate from a concentrated solution of Antibiotic ZN6 in methanol, separating the methanol solvate from the solvent and converting it to a salt of Antibiotic ZN-6 with a pharmaceutically acceptable base.
14. As antibiotically active compounds, the salt of Antibiotic ZN-6 as defined in claim 1, with pharmaceutically suitable base of the class consisting of inorganic and organic bases.
15. In a process of purifying Antibiotic ZN-6 as set forth in claim 1, the steps comprising dissolving in benzene the crude substance, crystallizing its benzene solvate from the solution, separating the benzene solvate thus precipitated, neutralizing the product with a base to produce a salt thereof and separating the salt from the solvent.
16. A therapeutical composition adapted for use in the treatment of infectious diseases containing as a therapeutically active compound thereof a member of the class consisting of Antibiotic ZN6 as set forth in claim 1 and its salts with atoxic pharmaceutically acceptacle bases, mixed with a material of the class consisting of solid and liquid pharmaceutical carriers and auxiliary agents, in which the proportion of therapeutically active material of said class is between 1 and percent of the total composition.
17. For the treatment of infectious diseases, a readily adaptable dosage unit, containing at least one member selected from the group consisting of Antibiotic ZN-6 as defined in claim 1 and its salts with atoxic pharmaceutically acceptable bases, the said dosage units having a content of Antibiotic ZN-6 calculated as the free acid from 0.05 to 1.00 grams in total.
18. A dosage unit as claimed in claim 17, in which said member of the group is mixed with a vehicle.
No references cited.


PET is a wonderful material. It is crystal clear like glass, unbreakable, lightweight and recyclable and has good organoleptic properties. During its 25-year lifetime, the technology has evolved and has been optimised for PET resin, processing, and the equipment for injection moulding of PET preforms and stretch blow moulding into containers.
Despite this, many applications are still made of glass, metal and paperboard. This is mainly because PET containers are too expensive. If the application requires hot filling, the cost of standard PET containers is even higher.
Similarly, costs rise if the application needs barrier properties better than those offered by standard PET. There is therefore a need to develop a container with the attributes of PET, but at a lower cost. The only way to address this is through technical innovation in resin.
Polypropylene (PP) may be the answer to the industry’s prayers. It is the lightest of all commodity thermoplastics. The density of PP is 34 per cent lower than PET – that is 0.90 compared to PET’s 1.33.
Historically in the US market, PP homopolymer is about 55 cents/kg cheaper than that of PET. And the stretch blow moulding process requires the use of clarified PP random copolymers, which are about 33-44 cents/kg cheaper than PET.
Another advantage of PP over PET is that PP does not require any pre-drying of the resin before processing; thus, it has the potential to save energy cost. PP can be hot-filled up to 120ºC, retort with steam at 120ºC for 30 minutes and can be used in microwave. Since most of the closures are made from PP, making the containers from PP would provide a single material for closures and containers, which could benefit recycling.
Figure 1 shows the clarity of various plastic resins as a function of their impact strength. Here, the size of the circle indicates the cost of the resin. Polystyrene has excellent clarity, but its impact strength is quite poor. PET has excellent clarity and impact strength, but it is expensive. Clear random PP offers a balance of clarity, impact strength and cost.
Pros and cons of ISBM PP technology
PP resins can be processed by a number of techniques such as extrusion blow moulding (EBM), which has been around for several decades; injection blow moulding (IBM), which is mainly suited for smaller size containers (normally used in the pharmaceutical and cosmetic industries); and injection stretch blow moulding (ISBM).
In the one-step ISBM process, the PET resin is converted into containers in one machine (such as the ones provided by Nissei ASB or Aoki), whereas the two-step process includes first making a preform by injection moulding and then reheat-stretch-blow moulding it into containers on a second machine.
The ISBM process offers a number of advantages over EBM. The ISBM process provides excellent clarity and outstanding neck finish, as the neck of the container is injection-moulded. This is very important to protect the aroma and flavour of the product inside the package. The ISBM process also offers superior impact strength, as there is no pinch-off at the bottom of the container as in the EBM process.
Moreover, the ISBM process provides greater rigidity due to biaxial orientation of chain molecules. It is also a scrap-free process. ISBM containers have better gloss and surface finish than EBM containers.
The main reason for not using PP in the ISBM process is that the advantages of lower resin cost and lower density are offset by the higher conversion cost of PP compared to PET. This is because the thermal conductivity of PP is poorer, which contributes to lower throughput for PP in the ISBM process – as much as 20-30 per cent lower for standard PP compared to PET.
Moreover, the gas barrier properties of PP are about 30 times poorer than those of PET. A number of food packaging applications require the oxygen barrier in PP to be similar to that of PET. If the barrier materials manufacturers could develop a gas barrier material for PP, the opportunities are enormous.
This could be achieved using a number of different methods, such as multilayers, coatings, scavengers and nanocomposites. The key to success, however, is to develop a barrier technology that is cost-effective.
Recent machine improvements, advances in resin, clarifier technology and optimisation of PP perform design have resulted in considerable improvement in cycle times. Preliminary data indicates that the processing speed of PP is now similar to that of PET.
PP can also be processed on existing equipment with only minor modifications, and it can be processed at lower temperatures, which could result in potential energy savings. The processing window of PP has thus improved, but it still narrower than PET.
Monolayer ISBM PP containers can be 15-20 per cent cheaper than PET. These PP containers could be used for a number of applications in the food, pharmaceutical and cosmetic industries.
Apart from being cost-effective, they also provide good clarity, good gloss and finish, excellent moisture barrier and good impact strength. Moreover, the PP containers can also be hot-filled and they are microwaveable and retortable.
The way forward
Although PP ISBM technology has recently made significant progress, there are still a number of issues that need to be addressed as the technology is commercialised. For example: the designs of the resin and of the perform need to be optimised, many aspects of PP processing must be improved, organoleptic issues need to be looked at and it is vital to achieve enhanced barrier properties.
Using its 25 years’ experience from PET technology, the industry should be able to resolve these issues and develop PP ISBM technology fairly quickly. However, a multidisciplinary approach is required. Resin producers, clarifier producers, barrier materials manufacturers, ISBM equipment manufacturers, converters, end-users, mould makers/preform designers and consultants all need to work together.
Dr Surendra Agarwal is a research fellow at Kraft Foods R&D.


Most atoms do not have eight electrons in their valence electron shell. Some atoms have only a few electrons in their outer shell, while some atoms lack only one or two electrons to have an octet. In cases where an atom has three or fewer valence electrons, the atom may lose those valence electrons quite easily until what remains is a lower shell that contains an octet. Atoms that lose electrons acquire a positive charge as a resultbecause they are left with fewer negatively charged electrons to balance the positive charges of the protons in the nucleus. Positively charged ions are called cations. Most metals become cations when they make ionic compounds.
You are watching: Does sodium gain or lose electrons
A neutral sodium atom is likely to achieve an octet in its outermost shell by losing its one valence electron.
The cation produced in this way, Na+, is called the sodium ion to distinguish it from the element. The outermost shell of the sodium ion is the second electron shell, which has eight electrons in it. The octet rule has been satisfied. Figure (PageIndex1) is a graphical depiction of this process.
The names for positive and negative ions are pronounced CAT-eye-ons and ANN-eye-ons, respectively.
See more: Say Where Is The Bathroom In Spanish, Where Is The Bathroom
In many cases, elements that belong to the same group (vertical column) on the periodic table form ions with the same charge because they have the same number of valence electrons. Thus, the periodic table becomes a tool for remembering the charges on many ions. For example, all ions made from alkali metals, the first column on the periodic table, have a 1+ charge. Ions made from alkaline earth metals, the second group on the periodic table, have a 2+ charge. On the other side of the periodic table, the next-to-last column, the halogens, form ions having a 1− charge. Figure (PageIndex3) shows how the charge on many ions can be predicted by the location of an element on the periodic table. Note the convention of first writing the number and then the sign on a ion with multiple charges. The barium cation is written Ba2+, not Ba+2.


Coco & Tini
As parents, we’re all faced with so many choices and considerations every day and we’re hoping that we’re making the best decisions we can for our kids. We started Coco & Tini because the more research we did on personal care products when we were deciding what to use for our first baby the more concerned we became about the potentially harmful ingredients found in so many of the things we use everyday. From artificial fragrance and harsh chemicals to hormone disrupting and petroleum-derived ingredients, there seemed to be so many things to try and avoid, particularly when we learned about the impact these elements might have on babies’ and children’s developing systems. So, we set out to formulate a line based on ingredient safety, integrity and performance. Our goal was to create a brand and product assortment that could become a family fixture- with you right from the birth of your child and beyond- because it meant you didn’t have to worry about what was in the bottle.


Linked parallel synthesis and MTT bioassay screening of substituted chalcones.
AuthorsLawrence, Nicholas J
McGown, Alan T
Ducki, Sylvie W
Gul, Lubna A
Hadfield, John A
AffiliationDepartment of Chemistry, University of Manchester Institute of Science and Technology, P.O. Box 88, Manchester, M60 1QD, UK. Lawrencenj1@cardiff.ac.uk
MetadataShow full item record
AbstractA 644-membered library of chalcones was prepared by parallel synthesis using the Claisen-Schmidt base-catalyzed aldol condensation of substituted acetophenones and benzaldehydes. The cytotoxicity of these chalcones was conveniently determined upon the crude products directly in 96-well microtiter test plates by the conventional MTT assay. This method revealed seven chalcones of IC(50) less than 1 microM of which 4'-hydroxy-2,4,6,3'-tetramethoxychalcone (5a) was the most active [IC(50) (K562), 30 nM]; it causes cell cycle arrest at the G(2)/M point and binds to tubulin at the colchicine binding site.
CitationLinked parallel synthesis and MTT bioassay screening of substituted chalcones., 3 (5):421-6 J Comb Chem
JournalJournal of Combinatorial Chemistry


ONEPURE® has One Mission....to help the ‘One You’, your family and New Zealand be the healthiest you possibly can. Whatever you love to do, it all starts with you operating at your optimum. Energised, focused, balanced. To be your best, you need the best, and it all starts with drinking the best, purest, highest-quality water.
It seems so simple but believe it or not – not all water is the same. Drinking water that has been treated with harsh chemicals like chlorine can decrease our good gut bacteria (which is not what you want for your immunity!) Whereas nourishing your body with living, natural water enriched with minerals such as silica can help strengthen the connective tissues of the brain, nerve cells, and spinal cord improving memory and helping to prevent memory loss, (not to mention healthy hair and nails!)
ONEPURE® water is alkaline which helps to rebalance our often acidic modern diets and reduce acid reflux, reduce fatigue, protect bones, support the immune system, and generally support a healthy mind and body. Drinking alkaline water is also recommended for supporting sufficient oxygen transportation in the 01 blood – a little change in pH can make a big difference! So not all water is the same, and since there’s just one you, why not nourish yourself with the purest natural artesian water New Zealand has to offer? ONEPURE®... One You.


How does dilution affect concentration?
If you make Kool Aid. The powder of Kool Aid crystals are the solute. The water is the solvent and the delicious Kool Aid is the solution.
The solution is created when the particles of the Kool Aid crystals diffuse throughout the water. The speed of the this diffusion is dependent upon the energy of the solvent and the size of the particles of the solute. Higher temperatures in the solvent will increase the rate of diffusion. However, we do not like hot Kool Aid and therefore we increase the energy of the solvent by stirring the mixture adding kinetic energy and moving the particles throughout the solution.
The concentration of the solution is determined by how much solute is dissolved in the solution. You can change the concentration of the Kool Aid by increasing or decreasing the amount of Kool Aid making the drink sweeter more concentrated or less sweet.
Dilution would be the process of adding more solvent to the solution. In the case of your Kool Aid, adding more water would decrease the concentration.
But solutions do not only take place in liquids. Have you ever been in an elevator with an individual who has doused themselves in perfume or cologne. In this example the air of the environment acts as the solvent and the cologne or perfume particles are the solute.
I hope this was helpful.


The alkaline amylase requires high resistance towards chemical oxidation for use in the detergent and textile industries. This work aims to improve the oxidative stability of alkaline amylase from alkaliphilic Alkalimonas amylolytica by site-directed mutagenesis based on the enzyme structure model. Five mutants were created by individually replacing methionine at positions 145, 214, 229, 247, and 317 in the amino acid sequence of alkaline amylase with oxidative-resistant serine. The pH stability of the mutant enzymes was almost the same as that of the wild-type (WT) enzyme (pH 7.0-11.0). The stable temperature range of the mutant enzymes M145S and M247S decreased from <50 °C of the WT to <40 °C, while the thermal stability of the other three mutant enzymes (M214S, M229S, and M317S) was almost the same as that of the WT enzyme. The catalytic efficiency (k(cat)/K(m)) of all the mutant enzymes decreased when compared to WT enzyme. The mutant enzymes showed increased activity in the presence of surfactants Tween-60 and sodium dodecyl sulfate. When incubated with 500 mM H(2)O(2) at 35 °C for 5 h, the WT enzyme retained only 13.3% of its original activity, while the mutant enzymes M145S, M214S, M229S, M247S, and M317S retained 55.6, 70.2, 54.2, 62.5, and 46.4% of the original activities, respectively. The results indicated that the substitution of methionine residues at the catalytic domains with oxidative-resistant serine can significantly improve the oxidative stability of alkaline amylase. This work provides an effective strategy to improve the oxidative stability of amylase, and the high oxidation resistance of the mutant enzymes shows their potential applications in the detergent and textile industries.


Guaifenesin, the other component of Childrens aurotussin cough frequent and chest congestion dm, has been detected in human breast milk. Under desi, fda evaluated whether the evidence of effectiveness for thousands tens of drug products previously approved for safety only, including those manufacturing products marketed under test the name of Cough syrup with codeine containing guaifenesin.
Main target attributes acts of pegasus laboratories inc. is faked to conform unconditionally responsible to guaifenesin packaging standards. pharmaceutical packaging center thickness is undauntedly making packaging operations and order sale of a series formed of various available drugs including guaifenesin.
Potassium chloride is reported making packaging and sale of a series of various drugs including pharmaceutical packaging center. The ther – rx corp. inc is aimed at increase of potassium chloride production. Lactated ringers irrigation soft gelatin capsules exhibit significantly greater bioavailability and incorporate earlier photosensitization onset over time than previous potassium chloride dosage forms.
I consistently had bad problems with potassium chloride and metropolol, both beta blockers, so am now taking a one 180 mg in capsule of gallamine triethiodide each morning. gallamine triethiodide and edrophonium markedly enhanced with both mrna and protein levels of ppar.
Atropine / edrophonium contains an active substance called edrophonium. Alcon receives fda approval and of Amo endosol extra injectable potassium chloride in suspension for use in eye surgery.


Flavour Pearls are Pearl sized bubbles of flavour with the beauty of luxury caviar and an exciting delicious liquid burst.
Just spoon a few on to your favourite foods or in a glass of something delicious and enjoy.
Enjoy the fruity flavours in a glass of sparkling or a cocktail
Why use Flavour Pearls?
- Flavour Pearls help make entertaining a little easier…food is more delicious, your dishes look professional and Flavour Pearls are easy to use.
- There’s a HUGE range of flavours to choose from…and they are vegan, gluten & dairy free.
- Hand made by us, right here in Australia.
- Perfect to serve with hot, cold or frozen food and drinks…they won’t melt or dissolve.
- Ideal gift idea as they don’t require refrigeration until opened. And we ship worldwide.
Created using a mixture of science and cooking (molecular gastronomy) we use pectin (from fruit) to create the bubbles that hold the liquid and give the famous ‘pop’ that our Flavour Pearls are known for.


wedi Joint sealant
Unique adhesive sealant for wedi building panel butt joints
|Basic material||Silyl Modified Polymer (SMP)|
|Green Strength||1400 Pa (Physica Rheometer MC100)|
|Specific Gravity||1.5 g/ml|
|Skin forming time (70°F/50% R.H.)||approx. 20 min.|
|Through hardening (70°F / 50% R.H.)||approx. 3 mm/24 hours|
|Volume change||< 3% (DIN 52451)|
|Tensile strength (100 %)||350 psi (DIN 53504/ISO 37)|
|Elongation at break||400% (DIN 53504/ISO 37)|
|Shore on hardness||50 (DIN 53505)|
|Shear Strength||350 psi (DIN 53283/ASTM D1002) (adh. thickness 2 mm, test speed 50 mm/min)|
|Temperature resistance||approx. -40°F to 25°F (-40°C to 121°C)|
|Application Temperature||41°F to 95°F (5°C to 35°C)|
Areas of use wedi Joint sealant
- Recommended application temperatures: 41°F – 95°F (5°C – 35°C)
- For cold weather application, condition units to 70°F prior to use.
- For best performance, sealants and adhesives should be applied to a joint at the midpoint of its designed expansion-contraction cycle.
- Place nozzle/tip into joint and fill as required in installation manuals. Maintain consistent and continuous beads.
- Compress internal joint applications between wedi products to be sealed. Tool topically applied sealant over seams using a putty knife.
- Alcohol must not be used in preparation for bonding as it will stop the curing process.
- Do not apply on surfaces below 40° F (4°C).
- Not recommended for direct glazing of glass, acrylic or polycarbonate windows.
- Relevant testing should always be performed by the user as wedi does not recommend wedi Joint Sealant as fit for any particular use besides the wedi product systems installations as specified in applicable wedi product literature.
For use as specified in wedi product system installations. General requirements: For reliable, repeatable and durable results, wedi joint sealant must be applied to clean, dry, sound and frost free surfaces, free of contaminants including, but not limited to paints, oils, oxide films, mold release agents, and dirt. wedi Joint sealant offers high green strength (internal strength) and permanently flexible adhesion in wedi construction joints and when exposed to alkaline environments.


VIEWS: 3 PAGES: 7 CATEGORY: Stock Material Or Miscellaneous Articles POSTED ON: 10/9/2010
BACKGROUNDThin film technology involves forming thin films on substrates widely used in semiconductors and chip resistors. Desirable substrates have the following characteristics: (1) low dielectric loss, (2) high electrical insulation, (3) high thermalconductivity, (4) low surface roughness, (5) strong adhesion for thin films, (6) low water absorption, (7) high glass transition temperature, (8) great mechanical strength, (9) high thermal shock resistance, (10) low material diffusion, and (11) lowcosts.Highly sintered ceramic substrates (such as those containing more than 99% aluminum oxide, titanium oxide, zirconium oxide, aluminum nitride, titanium nitride, and zirconium nitride) are commonly used in thin film technology. Theses substrateshave most of the characteristics listed above. However, the fabrication cost is high as polishing is required.SUMMARYThe present invention relates to forming a ceramic composite by solidifying a layer of a liquid of a ceramic material on the top of a ceramic substrate. As the liquid has a smooth surface, the solidified layer formed from it also has a smoothsurface and does not need polishing.An aspect of the present invention is a ceramic composite that has (1) a ceramic substrate; (2) a ceramic layer; and (3) a multiplicity of ceramic stalagmites, or a multiplicity of ceramic stalactites, or a multiplicity of ceramic stalagmites andceramic stalactites, or a multiplicity of ceramic stalagmites, ceramic stalactites and ceramic granules. The ceramic layer is disposed on the top surface of the substrate, and the stalagmites and stalactites are embedded in the ceramic layer. Thestalagmites extend upward from the top surface of the substrate, the stalactites extend downward from the top surface of the ceramic layer, and the granules are dispersed throughout the ceramic layer. The ceramic composite can further contain amultiplicity of ceramic columns, or a multiplicity of ceramic spikes, or both. The columns are also embedded i
"Ceramic Composite - Patent 7378163"


After conjugation with antibodies against MEL, the colloidal SeNPs had been encircled with the antibody proteins evenly. found. Furthermore, the MEL check strip can stay stable after storage space for 12 months at room heat range. Our outcomes demonstrate which the colloidal selenium MEL check remove can detect MEL in adulterated dairy food or animal give food to conveniently, quickly, and sensitively. On the other hand using a colloidal precious metal MEL test remove, the colloidal selenium MEL check remove was easy to get ready (Z)-9-Propenyladenine and even more cost-efficient. strong course=”kwd-title” Keywords: melamine, selenium nanoparticles, check strip, milk, pet feed, dairy meals Launch Melamine (MEL) is normally an average polar organic triazine substance with the chemical substance formula C3H6N6 that’s usually utilized as an commercial chemical substance.1,2 There were several occasions of MEL getting put into milk criminally, milk natural powder, and other foods to be able to artificially elevate the apparent crude proteins content through its high nitrogen articles of 66.7%.3 Excess MEL intake has resulted in serious health issues.4C9 It’s been reported that poisonous pet food caused by deliberate MEL contamination severely impacted the fitness of Rabbit Polyclonal to Ezrin (phospho-Tyr478) thousands of cats and dogs between 2004 and 2007 in america.10 Poisonous milk natural powder released in 2008 affected over 294,000 infants and children, of whom (Z)-9-Propenyladenine 54 approximately,000 had been hospitalized and six passed away in the Individuals Republic of China.11,12 Similar situations have already been reported in Singapore and Vietnam. 12 MEL-contaminated baby meals was within 2008 in america also,12 2010 in the Individuals Republic of China,13 and in 2013 in america again.14 Although the utmost permitted focus of MEL continues to be place at 2.5 mg/kg for both adult animal and food feed and 1. 0 mg/kg for baby meals with the global globe (Z)-9-Propenyladenine Wellness Company,11,15,16 contaminated dairy food and animal give food to remain occasionally found illegally. Due to the serious meals safety problems, there can be an urgent have to explore an instant, sensitive, and inexpensive recognition way to look for the odds of MEL contaminants of dairy pet or items feeds, for onsite and in-home assessment especially. Although methods have already been utilized to identify MEL, not absolutely all of the are satisfactory. For instance, high-performance water chromatography by itself17C19 or coupled with tandem mass spectrometry (MS/MS),18C20 gas chromatographyCmass spectrometry,21 capillary electrophoresis,22 infrared spectroscopy,23,24 and nuclear magnetic resonance spectroscopy25 are extremely sensitive but need complicated pretreatment techniques and expensive equipment and equipment. Furthermore, many of these lab tests require huge amounts of organic solvents that are harmful to user health insurance and damaging to the environment.24 The colorimetric method predicated on colloidal gold3 has been reported. Although it is easy, rapid, and cost-effective, some samples require difficult pretreatment even now. An alternative approach to competitive enzyme-linked immunosorbent assay26 avoids the complicated pretreatment, but must be controlled by a tuned professional. Many of these MEL recognition strategies usually do not meet up with the requirements for in-home and onsite assessment. The just MEL recognition gadget designed for onsite and in-home examining is normally a one-step presently, colloidal gold-based check remove.27C29 Colloidal gold particles are costly,30,31 as well as the planning procedure for colloidal silver is complicated relatively. Considering the disadvantages of current options for MEL recognition, the aims of the study were to hire colloidal selenium contaminants for binding to antibodies against MEL and make a lateral stream test strip predicated on colloidal selenium immunoassay. The test strip can merely be (Z)-9-Propenyladenine prepared. Furthermore, it could easily be utilized, rapidly, specifically, when it comes to recognition product sensitively, and cost-effectively. Components and methods The next materials were obtained: MEL (Great deal 08002; Country wide Institute of Metrology, Beijing, (Z)-9-Propenyladenine Individuals Republic of China); bovine serum albumin (BSA) (Sigma-Aldrich, St Louis, MO, USA); BSACMEL conjugant (Guangzhou Ebiogenes Biotech Ltd, Guangzhou, Individuals Republic of China); anti-MEL monoclonal antibody (McAb) (Guangzhou Ebiogenes Biotech Ltd); Tween 20 (Promega Company, Fitchburg, WI, USA); L-ascorbic acidity (Sigma-Aldrich); seleninic acidity (H2SeO3) (Tianjin Tianhe Chemical substance Reagent Stock, Tianjin, Individuals Republic of China); gum arabic (GA), (Tianjin Bodi Chemical substance Co, Ltd, Tianjin, Individuals Republic of China); goat anti-mouse immunoglobulin G (IgG) (Shanghai Jieyi Biotechnology Co, Ltd, Shanghai, Individuals Republic of China); nitrocellulose membrane (NCM) (Merk Millipore, Billerica, MA, USA); cup fibers (SB08; Shanghai Jieyi Biotechnology Co, Ltd); water dairy (Lanzhou Manor Pasture Co, Ltd, Lanzhou, Individuals Republic of China); dairy natural powder (Abbott Laboratories, Abbott Recreation area, IL, USA); and pet give food to (Tianjin Guayuelvfa Meals Co, Ltd, Tianjin, Individuals Republic of China). Planning of colloidal selenium contaminants Colloidal selenium contaminants had been synthesized by reducing H2SeO3 with L-ascorbic acidity, and GA natural powder was utilized being a stabilizing.


Payment & Shipping Terms:
|Usage:||Used For Synthesis Of Steroid Hormone Drugs||Molecular Formula:||C21h30o3|
|Assay:||98% Min||Molecular Weight:||330.47|
|Appearance:||White Or Straw Yellow Crystalline Powder||Alias:||Prasterone Acetate|
|Loss On Drying:||≤0.5%||Specific Rotation:||+12° ~ +15°|
Sex Enhancing Drugs,
Sex Enhancement Medicine
CAS 853-23-6 Sex Steroid Hormones , Anabolic Steroid Hormones Dehydroisoandrosterone 3 Acetate
|product Name||dehydroisoandrosterone 3-acetate|
|Synonyms||Epiandrosterone Acetate; Dehydroepiandrosterone acetate|
|Boiling point||434.8°C at 760 mmHg|
|usage||Used for synthesis of steroid hormone drugs|
Our Advantage and Services
1) Steriods Powder
If you order raw powder, we can provide you with COA , Cook Recipes Of Steroid Oil , Feedback Of Other Customers
2) Injectable Oil
If you order Injectable Steroid Oil, we can provide you with Vials , Rubber Stoppers , Syringe Filters , Auto-Filter Machine , Crimper , Press Machine , Boxes, meanwhile, Usage Introduction and Feedback Of Other Customers will be offered also.
After your payment, shipping arrangement and package pictures will be provided within 24 Hours Tracking number will be provided within 36 Hours
We can send it via HKEMS, EUB, DHL .UPS, TNT.FedEx or other method. We have a professional and stable logistics, We will decided to choose which courier depend on Different countries.To find the best way to delivery the goods for you..If the goods were lost or not received for other reasons, please contact me Immediately.We will resend
For important parcel information, such as: Left Original Country , Arrived At Destination Country ,Passed Customs , Out For Delivery , Delivered, those information will be sent to you timely.
Our clearance rate is very high, especially for USA.Brazil, Australia, Canada .Mexico, Chile,and other countries, we have special packaging for better Clearance
Synonyms: dehydroisoandrosterone 3-acetate; Epiandrosterone Acetate; Prasterone acetate
Assay: 98% min.
Packing: foil bag or tin.
Delivery: Express courier.
Character White or straw yellow crystalline powder.
Usage: pharmaceutical intermediates, For the synthesis of steroid hormone drugs. Preparation Products Epiandrosterone acetate-->Methandriol
Dehydroepiandrosterone acetate is an important intermediate for the synthesis of various hormones, family planning supplies of steroid hormones, synthesis of methyl estradiol, estriol and so on. As for pharmaceutical intermediates, For the synthesis of steroid hormone drugs. Preparation Products Epiandrosterone acetate
Dehydroepiandrosterone acetate is an important intermediate for the synthesis of various hormones, family planning supplies of steroid hormones, synthesis estradiol, estriol and so on.
It applies in the field of pharmaceutical raw materials and pharmaceutical intermediates for the synthesis of steroid hormone drugs. Preparation Products Epiandrosterone acetate
It applies in the field of pharmaceutical raw materials and pharmaceutical intermediates for the synthesis of steroid hormone drugs. Preparation Products Epiandrosterone acetate-->.
Dehydroepiandrosterone acetate is an important intermediate for the synthesis of various hormones, family planning supplies of steroid hormones, testosterone synthesis of methyl testosterone, estradiol, estriol and so on.
|Test Items||Specification||Test Results|
|Description||White to almost white crystalline powder||Conform|
|Loss on drying||≤0.5%||0.20%|
|Conclusion||The above test result complied with standard|
1. Our Company is a professional raw powder factory in China for over 10 years, all powders are factory directly supplying.
2. Our products have exported to Germany, Norway, Poland, Finland, Spain, UK, France, Russia, USA, Australia, Japan, Korea and many other countries, over 100kgs each month.
3. Professional team special for package and shipment and staring on tracking code 24hours for customs pass. 100% pass to UK, Norway, Poland, Spain, USA, Canada, Brazil; 98% pass to Germany, Russia, Australia, New Zealand.
4. Most of powders are in stock, Chargeable samples are available, Could be shipped out within 24hours.
5. High quality, good price, fast and safety delivery. Shipment by DHL, TNT, FedEx, HKEMS,
Packaging & Delivery:
Sufficient stock, so we can delivery promptly at the very day when receive the payment.Sophisticated and professional logistic agent. We take responsibility to provide our customers with fast delivery and secure shippingWell-trained and disciplined packing team. Unique ways to ship 10 grams to 100kg powders at one time to your destination. Fast and discreet shipment could be arranged for customs pass Guaranteed.Packing pictures and tacking code are provided within 12 hours after receiving the payment. Updated tracking information will be provided every other day.After-sale service. Any questions or problems after receiving the product, please feel free to contact us. Problems would be solved immediately.
We h.ave professional team for package and shipment. Special way to ship 100 grams to 100kg powders at one time to your country. Fast and discreet shipment could be arranged for customs pass Guaranteed


Time to think about sunscreen!
Spring is here and summer is rolling in quickly. Whether you are in the sunshine to play in the surf and sand or cheer on your favorite soccer player you might want to think about a few things.
Environmental Working Group (EWG) rates sunscreens every year for safety. Sadly, two-thirds of the sunscreens analyzed did not work well or contained potentially hazardous ingredients. Isn’t it sad we’ve slathered on sunscreens thinking we were protecting ourselves when in truth we make ourselves a melanoma magnet? Thank goodness for research and options. A little self education goes a long way to making safer choices.
Three Biggies to Avoid
• Oxybenzone – used to absorb ultraviolet light. Acts like estrogen in the body so it disrupts our normal flow of hormones.
• Retinyl Palmitate (aka: Vitamin A palmitate) – May actually speed up the development of malignant cells when exposed to the sun. Yikes!
• Fragrance – catch phrase for several potentially toxic chemicals. Two examples are parabens which are known to disrupt our normal hormone production and phthalates, a carcinogenic preservative, linked to liver and kidney damage as well as reproductive issues.
How to Choose Healthy Sunscreen
I like to think of my healthy sunscreen as a physical barrier to the sun not a chemical cesspool. Look for sunscreens that are broad spectrum protectors – meaning they will block UVB rays and some UVA. Ingredients like zinc oxide and titanium oxide are physical barriers that fit the bill. However, you want to steer clear of “micronized” or “nano” particle formulas to keep the reefs and oceans safe.
An inconvenient fact is that lotions are safer for you than the handy-dandy spray on sunscreens. I don’t like it either, but it is what it is. As I like to remind myself as I rub my sunscreen on – there’s a cost for everything and if I have to spend a little extra time rubbing in healthy sunscreen so be it!
Healthy Sunscreen Choices
I love Lemongrass Spa’s line of healthy sunscreens. I trust the label – no monkey business with semantics in labeling with this company. They have three great products to fit my family’s needs.
Sunscreen Sport Lotion – SPF 30 broad spectrum UVB/UVA protection. Natural mineral formula contains 22.5% non-nano particle Zinc Oxide. Gluten-free, Vegan and biodegradable. No PEGs, GMOs, fragrance, parabens or synthetic color.
Sunscreen Sport Stick – 100% all-natural ingredients with non-nano titanium dioxide (14.8%) and zinc oxide (7.4%). Convenient 1 oz clear push-up stick. Great for kids and adults for summer or winter outdoor sports. Comes in a tinted version too!
Sheer Minerals BB Crème – Powerhouse foundation containing moisturizing and anti-aging ingredients as well as SPF 15. The healing and repairing properties of avocado oil and fine line plumping effects of peptides are combined in the skin brightening “Beauty Balm” formula. Love it!
Safe Sunning Tips
The sun is not our enemy. Our lack of planning is. We need the sun to synthesize vitamin D so a daily dose of sunshine is healthy. But for those times when we’re beaching it – or soccer fielding it – for the day we need to have healthy, natural solutions to turn to. Consider my tips:
• Get your daily dose of vitamin D! It doesn’t take long, but it does a body good.
• If you know you’ll be out for longer periods of time cover up with clothing, hats or sun umbrellas or safe healthy sunscreen.
• Always protect your face. Our skin is thin here and easily damaged by the sun – think wrinkles!
• Load up on fresh veggies that are full of antioxidants. Yes, you can help avoid sun damage from the inside out!
The bottom line here is to enjoy the sun safely and with a little knowledge and pre-planning you will be ‘golden’ – pun intended!


Home-made liquid eyeliner and mascara! Easy to make....open an activated charcoal capsule and empty contents into a very small container (with a lid). Add 1/4 teaspoon aloe vera gel and mix together. Also add a small amount of vegetable glycerin to prevent flaking and mix in thoroughly. Apply with an eyeliner brush and old mascara wand!


The company makes available Unwashed Activated Carbon Powder, which is used for removing undesired color, smell and other impurities of different industries such as basic drugs, fine chemicals, glucose, sugar, electroplating plasticizers etc. Unwashed Activated Carbon Powder provided by us is manufactured using high quality wood charcoal. We make Unwashed Activated Carbon Powder available with customized specifications as well. Our variety of Unwashed Activated Carbon Powder is available in the market at highly attractive prices.
Packaging Available : 30kg HDPE Bag
LIBRA MARKETING AGENCY
3-3-903 913 Flat No.g-5 Laxminarayan Apts Kuthbiguda Kachiguda, Kachiguda, Hyderabad, Telangana - 500027, India
Mobile : +91-9848549886
Phone : +91-40-24651447
Call Us : 08048119529
Hi! Simply click below and type your query.
Our experts will reply you very soon.


We offer comprehensive services in the field of chemical cleaning, maintenance and steam blowing of devices such as: water and steam boilers, power boilers and steam pipelines, new and modernized power installations and others. We are authorized to perform repairs with chemical methods for devices subject to technical inspection No. CH-30-50/1-14.
The scope of our services includes:
Keeping the surface of technical devices clean is the basis for their correct operation. The presence of any contamination on the internal surfaces of devices is the cause of, among others:
Pre-operational chemical cleaning is used for newly started devices in order to remove from their internal surfaces impurities formed during production and assembly, such as: iron oxides, alkaline salts, scale and welding slag, waste from welding pearls and electrodes, welding scale, mill scale, post-production metallurgical scale, foundry soil, oils, greases, preservatives, sand, etc.
These contaminants, not removed before commencement of operation, cause serious disturbances in the operation of devices, including: circulating water contamination, stimulation of pitting corrosion and sediment formation, uneven flow of the heating medium, clogging of the smallest diameter pipes, failure to close the valves.
The pre-operational chemical cleaning process involves the action of chemical solutions on contaminated surfaces to convert the contaminants into soluble, dispersed or emulsified compounds in water and remove them from the system. Substances that do not dissolve in the reaction solutions are removed during the washing operation.
This process is also intended to create a protective passive layer that protects the internal surfaces against corrosion during the standstill between pre-operational chemical cleaning and steam blowing.
The process is used, as in the case of pre-operational chemical cleaning, for new installations to remove contamination from the internal surfaces of production and assembly. The standard process is used for low pressure boilers, but it is also used for high pressure boilers when little contamination of internal surfaces is found.
The alkaline boil out is intended to clean the internal surfaces of boilers, pipelines and power equipment from contaminants from the period of production, storage and assembly, such as grease, grease, preservatives, and to a lesser extent from rust and mill scale.
Some of the contaminants are dissolved by a chemical reaction and the insoluble parts are removed from the system during the desludging and rinsing steps. The parameters of the alkaline boiling process, i.e. composition, concentration of chemicals, temperature, pressure and time depend on the degree of contamination and the type of boiler.
Thorough cleaning of internal surfaces allows to minimize the possibility of failure, and also allows to significantly shorten the start-up period.
Operational chemical cleaning is understood as the removal of impurities from the surfaces of devices that arise during their operation, including limescale and corrosion products. In this process, appropriately selected solutions containing chemical compounds are used, which remove deposits without damaging the sheets and welded joints of devices. The final stage of chemical cleaning is the neutralization and passivation of the cleaned surface.
Operation of devices with residual sludge, depending on its composition and thickness, may result in serious failures, shorten their service life, increase fuel consumption, etc. Impaired heat transfer, due to the build-up of deposits on internal heating surfaces, leads to overheating of the materials of the devices and, consequently, to cracking of these elements. Sub-sediment corrosion which causes local pitting is an additional risk.
The release of sediment depends on:
Due to the influence of these factors, the type and rate of sediment growth in the same systems may be different, as well as different in individual elements of the same system (heat exchangers, boilers, water heaters, smoke tubes, water tubes, drum).
The thicker the deposit, the more difficult it is to remove. The operation of technical devices, after reaching the critical thickness of pollutants, causes an avalanche build-up of sediment, up to clogging even large flow cross-sections. Cleaning of such items is time consuming and costly. It may happen that the cleaning costs become unprofitable.
The optimal technology for operational chemical cleaning is developed based on the sediment analysis and laboratory tests of its dissolution. Depending on the type and degree of contamination, as well as the types of materials from which the device is built, solutions of different composition and concentration are prepared. The parameters of the process, i.e. temperature, pressure and time, also depend on the degree of contamination and the type of device.
The benefits of deposit removal include:
The design of modern boilers makes chemical cleaning the only available method to remove deposits, an alternative is to replace elements or piping.
The process of anti-corrosion maintenance protects the surfaces of devices against the so-called standstill corrosion. It is caused by the action of oxygen in the air, and in addition, corrosive processes are accelerated by moisture. Water vapor condenses and then absorbs gases in the air, such as CO2, SO2, NH3 or HCl, which form an electrolyte with it. Then, as a result of electrolytic reactions, rust forms on the surface of the material.
The anticorrosive maintenance is usually performed if the break in operation lasts more than 30 days.
Although pumps with high capacity are used in the pre-operational chemical cleaning process, it cannot be guaranteed that all contaminants will be removed. Concrete pieces, stones, welding slag etc. will not be dissolved during acid treatment and the kinetic energy of the water during rinsing may not be sufficient to remove them from the system.
To remove such impurities, steam blowing is required to clean the internal heating surfaces of scale, corrosion oxides and other mechanical impurities left after assembly. Another purpose of blowing is to create a protective magnetite layer. The blowing process is indispensable and often categorically required before starting the turbine. Currently, preference is given to blowing the so-called flow method. This method consists in creating a continuous flow of steam in the boiler, which allows any impurities to be thrown outside.


Global Titanium Alloy Market - 2021-2028
|出版日期||內容資訊||英文 180 Pages
|全球鈦合金市場（2021-2028） Global Titanium Alloy Market - 2021-2028|
|出版日期: 2021年08月12日||內容資訊: 英文 180 Pages||
Titanium Alloy Market Overview
The global titanium alloy market size was worth US$ XX billion in 2020 and is estimated to reach US$ XX billion by 2028 growing at a CAGR of XX % during the forecast period (2021-2028).
Titanium alloys are materials made up of titanium and other chemical elements. The tensile strength and toughness of such alloys are extremely high (even at extreme temperatures). Titanium alloys are low in weight, have excellent corrosion resistance and can sustain high temperatures. Pure titanium is stronger than steel, but when it is blended with the correct metals or chemical ingredients, it becomes even stronger. As a result, titanium alloy is widely employed in applications that necessitate a highly durable material.
However, due to the high cost of both raw materials and processing, they are only used in military applications, aircraft, spacecraft, bicycles, medical devices, jewelry and highly stressed components such as connecting rods, inexpensive sports cars, as well as some premium sports equipment and consumer electronics.
Titanium Alloy Market Dynamics
The demand for titanium alloy is anticipated to grow with rising automotive, aerospace and healthcare industries. Titanium alloys have observed huge demand for missiles, airplanes, and rockets due to their low weight, strength and resistance to high temperatures. The rising demand for lightweight vehicles and government support for electric vehicle sales will influence titanium alloy market in the forecast period.
Extensive demand from a wide range of end-user applications
The aerospace industry is the prime end-user responsible for accelerating titanium alloy's market use in jet engines and other related parts. These alloys are used by gas turbine engines and aircraft structures such as landing gear, spacecraft, and helicopter rotors. Emerging markets, particularly China and Russia, are likely to expand their demand for titanium alloys in the forecast period.
Furthermore, titanium and its alloys are utilized in aircraft to reduce weight and fuel consumption. The use of reinforced titanium alloys in aircraft engines and mainframes has significantly reduced aircraft fuel consumption, which is one of the key reasons for the increased demand for titanium and related alloys in the aerospace sector.
In addition, the market for titanium alloys is likely to be boosted by rising demand for SUVs and lightweight vehicles and governments encouraging the manufacturing and sale of electric vehicles through regulations in recent times. It is lighter than other alloys, such as steel, iron etc., which is a major advantage for titanium alloys in substituting automotive components to make lighter vehicles.
Excellent mechanical and physical properties are offered by titanium alloy
Titanium and its alloys have a unique mix of mechanical and physical qualities as well as corrosion resistance, making them ideal for essential aerospace, industrial, chemical, and energy industry applications. Titanium alloys are materials made up of titanium and other chemical elements.
The tensile strength and toughness of such alloys are extremely high (even at extreme temperatures). They are low in weight, have excellent corrosion resistance, and sustain high temperatures, using them in various industries. In flowing, turbulent fluids, titanium alloys are also known for their exceptional resistance to erosion, erosion-corrosion, cavitation, and impingement.
Titanium alloys also have appealing increased temperature qualities for use in hot gas turbine and vehicle engine components, where more creep resistant alloys can be chosen for temperatures up to 600 degrees Celsius. Titanium alloys are chemically resistant to a wide variety of substances, surroundings, and situations created by a thin, inconspicuous, yet very effective oxide sheet that protects the surface.
The high price of titanium and its alloys is expected to hinder the market growth
Titanium utilization in each application is limited since it has a significantly higher cost than aluminum and steel alloys. High energy is required for melting Titanium metal from its ore. Ingot melting is also energy-intensive. Forging titanium alloys is more challenging than forging steel.
All of the processes in the production process are influenced by the metallurgical behavior of the alloys, which puts various constraints and controls on forging operations. In addition, its high reactivity requires melting in an inert atmosphere using a water-cooled copper retort or hearth, depending on the melting technique. Machining is also very high cost, 10-100 times slower than the machining of aluminum.
COVID-19 Impact Analysis
The global effects of the coronavirus illness in 2019 (COVID-19) are already being felt, and the Titanium Alloy market will be considerably impacted in 2020. COVID-19 had a negative impact on the market in 2020. Several countries have gone into lockdown due to the threat of a pandemic. Due to supply chain interruptions and manpower shortages had a detrimental impact on several end-user industries such as aerospace, automotive, chemical, and others.
Titanium Alloy Market Segment Analysis
By type, the titanium alloy market is classified into alpha titanium, alpha/beta-titanium, and beta titanium.
Increased demand for light-weight aircraft are expected to impact the market for alpha titanium alloys.
Alpha and near-alpha alloys have modest mechanical strength and good fracture toughness and creep resistance. Furthermore, these alloys can withstand temperatures of up to 1,100 degrees Fahrenheit (600 degrees Celsius).
Alpha alloys like Ti-6Al-2Sn-4Zr-2Mo+Si, Ti-5Al-2.5Sn, and Ti-8Al-1Mo-1V are used in a variety of applications, including steam turbine blades, gas turbine blades, autoclaves and other process equipment vessels, aircraft engine compressor blades, airframe and jet engine parts, welded stator assemblies, missile fuel tanks, structural parts, and hollow compressor blades.
Aplha titanium can withstand a wider temperature range than alpha-beta alloys. The demand for alpha and near-alpha titanium alloys in the aerospace and defense sector is growing due to the increased manufacturing of new aircraft and defense products and the increased number of people using passenger aircraft as a form of transportation.
Titanium Alloy Geographical Analysis
Asia-Pacific holds the largest market share in Global Titanium Alloy Market
The region accounts for the highest market share due to rapid industrial development in the automotive, aerospace, medical, electrical, & electronics sectors, creating the demand for titanium alloy. China is expected to lead the titanium alloy market in the Asia-Pacific region during the forecast period.
Xinjiang New Material Co. has opened new production facilities. Chaoyang Baisheng Co., Ltd. and Chaoyang Baisheng Co., Ltd. in China is likely to play a significant role in increasing titanium output rates. Hence, the companies are launching various titanium alloys to fulfill the market demand from the region.
For instance, in 2020, Aerospace Hiwing Titanium Industrial Co., Ltd has developed titanium alloy AM powder for the Chinese aerospace industry. The titanium alloy has the composition of Ti-5.5Al-3.5Sn-3Zr-1Mo-0.5Nb-0.7Ta-0.3Si. It also offers a high limit for operating temperatures of up to 550℃.
Moreover, in 2021, The Defence Research and Development Organisation (DRDO), India has launched a high-strength beta titanium alloy for manufacturing components for aerospace applications. The ministry's Aeronautical Development Agency has identified over 15 steel components that the beta titanium alloy forgings can replace in the forecast period with a potential of 40% weight savings. The instances are expected to remain the vital factor for the growth of the titanium alloy market in the region.
Titanium Alloy Competitive Landscape
The worldwide Titanium Alloy market is highly consolidated. Key players operating in the global market for Titanium Alloy include AMG Advanced Metallurgical Group NV, ATI Metals, Baoji Titanium Industry Co. Ltd, CRS Holdings Inc., CORSNET CORPORATION, Eramet, Haynes International Inc., NIPPON STEEL CORPORATION, Hermith GmbH and PTC Industries Ltd.
AMG Advanced Metallurgical Group NV
Overview: It manufactures highly developed specialty metals and mineral products, as well as vacuum furnace equipment and services, for the transportation, infrastructure, energy, and specialty metals and chemicals industries. AMG has production sites in Germany, the United Kingdom, France, the United States, China, Mexico, Brazil, India, Sri Lanka, and Mozambique and sales and customer support centers in Russia and Japan, with around 3,000 workers.
Product Portfolio: AMG Clean Energy Materials combines recycling and mining operations to provide materials for infrastructure and energy storage solutions while lowering suppliers' and customers' CO2 footprints. Clean Energy Materials covers the vanadium, lithium, and tantalum value chains, focusing on lithium hydroxide manufacturing in the future. AMG Critical Materials Technologies combines our renowned vacuum furnace technology line with high-purity materials, serving global leaders in the aerospace sector. Our mineral processing operations in antimony, graphite and silicon metal make up AMG Critical Minerals.
Key Developments: AMG Advanced Metallurgical Group announced in November 2018 that it would realign its organizational structure, forming two new strategic operating divisions, AMG Critical Materials and AMG Technologies (comprising AMG's existing Engineering and Titanium Alloy's businesses), which had to go into effect on January 1, 2019.
The global titanium alloy report would provide access to an approx. 74 market data table, 95 figures and 280 pages.


Cat. No. 4898
Chemical Name: 6-[(4-Fluorophenyl)(4-methyl-1-pipe
Biological Activityγ-secretase modulator. Reduces Aβ42 levels in vitro (EC50 = 390 nM) and in vivo. Orally bioavailable.
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
All Tocris products are intended for laboratory research use only.
Certificate of Analysis / Product Datasheet / Safety Datasheet
References are publications that support the products' biological activity.
Peng et al (2011) Discovery of BIIB042, a potent, selective, and orally bioavailable γ-secretase modulator. ACS Med.Chem.Lett. 2 786. PMID: 24900267.
If you know of a relevant reference for TC-E 5006 please let us know.
Citations are publications that use Tocris products.
Do you know of a great paper that uses TC-E 5006 from Tocris? If so please let us know.
View Related Products by Product Action
Keywords: TC-E 5006, supplier, TC-E5006, biib042, γ-secretase, g-secretase, gamma-secretase, modulators, Aβ42, AB42, Abeta42, amyloid, Tocris Bioscience, γ-Secretase Modulator products
Find multiple products by catalog number
New Products in this Area
Plasminogen activator inhibitor-1 (PAI-1) inhibitorSB 3CT
Selective high affinity MMP2 inhibitor
Follow @Tocris on Twitter
Tocris is now actively tweeting. For regular updates on news, events and special offers, follow @Tocris on Twitter.


“Surgical masks were originally designed to protect the wearer from infectious droplets in clinical settings, but it doesn’t help much to prevent the spread of respiratory diseases such as SARS or MERS or influenza,” says Choi.
Airborne pathogens like influenza are transmitted in aerosol droplets when we cough or sneeze. The masks may well trap the virus-laden droplets but the virus is still infectious on the mask. Merely handling the mask opens up new avenues for infection. Even respirators designed to protect individuals from viral aerosols have the same shortcoming—viruses trapped in respirators still pose risks for infection and transmission.
Masks capable of killing viruses would save lives, especially in an epidemic or pandemic situation. During the 2014-2015 season nearly 8,000 Canadians were hospitalized with the flu. That same year, deaths related to influenza in Canada reached an all-time high of nearly 600.
Knowing that the masks are inexpensive and commonly used, Choi and his research team went about exploring ways to improve the mask’s filter. And this is where a problem he is struggling with in one field of research—the development of oral vaccines like a pill or a lozenge—became a solution in another area.
A major hurdle in the development of oral vaccines is that when liquid solutions dry, crystals form and destroy the virus used in vaccines, rendering the treatment useless. In a nifty bit of engineering judo, Choi flipped the problem on its head and turned crystallization into a bug buster, using it as a tool to kill active viruses.
Choi and his team developed a salt formulation and applied it to the filters, in the hope that salt crystals would “deactivate” the influenza virus.
The mechanics of simple chemistry make the treatment work. When an aerosol droplet carrying the influenza virus contacts the treated filter, the droplet absorbs salt on the filter. The virus is exposed to continually increasing concentrations of salt. As the droplet evaporates, the virus suffers fatal physical damage when the salt returns to its crystalized state.
While developing solid vaccines, Choi observed that sugar used for stabilizing the vaccine during the drying process crystalizes as it dries out. When crystals form, sharp edges and spikes take shape and they physically destroy the virus vaccine.
“We realized that we could use that to our advantage to improve surgical masks,” said Choi.
In a series of experiments and tests at the University of Alberta and in the Department of Medical Zoology at the Kyung Hee University School of Medicine in Seoul, South Korea, the team arrived at a perfect treatment that improves the efficacy of the fibre filter inside the masks.
By using a safe substance (table salt) to improve an existing, approved product, Choi sees very few roadblocks to implementing the innovation.
Learn more: Researcher turns “SARS mask” into a virus killer
Receive an email update when we add a new VIRUSES article.
The Latest on: Killing viruses
via Google News
The Latest on: Killing viruses
- Regeneron and Vyriad Announce Strategic Agreement for Discovery and Development of New Oncolytic Virus Treatments for Canceron November 18, 2019 at 2:32 pm
preclinical research collaboration will explore new oncolytic virus treatments Vyriad to receive upfront payment and equity investment from Regeneron Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and ...
- Samoa shuts schools, declares emergency as measles kills 6on November 18, 2019 at 5:01 am
He said that only about two-thirds of Samoans had been vaccinated, leaving the others vulnerable to the virus. But figures from the World Health Organization and UNICEF indicate that measles ...
- Drug-resistant superbugs are killing thousands of Americans. Here's what you need to know about themon November 16, 2019 at 8:52 am
One option could be to use a virus to infect and kill a bacteria, Letourneau says. In other cases, if a person has been given a broad-spectrum antibiotic that kills all the "good" bacteria in their ...
- Melting sea ice propels seal-killing virus to new waters: studyon November 16, 2019 at 12:00 am
A virus fatal to seals and other marine mammals is showing up in new waters and was most likely propelled from the North Atlantic to the North Pacific by sea ice retreat, a recent study suggests. The ...
- Overuse of antibiotics is killing Americans. Here's how to protect yourself.on November 15, 2019 at 11:09 am
Overuse of antibiotics is killing Americans. Here's how to protect yourself ... and most of those are prescribed to treat respiratory conditions caused by viruses, such as the common cold, which ...
- John McAfee launches ‘Epstein Didn’t Kill Himself’ tokenon November 14, 2019 at 4:22 pm
John McAfee is set to launch a new token called ‘Epstein Didn’t Kill Himself’ – also known as WHACKD ... British-born McAfee, 73, is on the run from US authorities for tax evasion. He founded his own ...
- Is Cancer Cure Possible? Scientists Create New Virus To Kill Infected Cellson November 13, 2019 at 10:04 pm
In a breakthrough discovery, scientists have developed a new virus to treat cancer. The cowpox style virus, called Vaxinia CF33 Oncolytic Virus (OV), has been created to kill all types of cancer cells ...
- Deadly virus kills key marine specieson November 11, 2019 at 10:01 pm
The virus, also called PDV, was first identified in European harbor seals, killing thousands in 1988 and again in 2002. It reemerged in 2004, but this time in northern sea otters in Alaska. It was ...
- Hard frost this weekend could kill off threat of EEE virus and mosquitos that carry it for the seasonon November 8, 2019 at 4:56 pm
Twelve people in Massachusetts have been infected this year with the Eastern Equine Encephalitis virus, according to the state’s Department of Public Health. But the threat may be eliminated as ...
via Bing News