CN1733704A - Synthesis and biological and pharmacological action of betaine salicylate - Google Patents
Synthesis and biological and pharmacological action of betaine salicylate Download PDFInfo
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- CN1733704A CN1733704A CN 200410050998 CN200410050998A CN1733704A CN 1733704 A CN1733704 A CN 1733704A CN 200410050998 CN200410050998 CN 200410050998 CN 200410050998 A CN200410050998 A CN 200410050998A CN 1733704 A CN1733704 A CN 1733704A
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- ointment
- whitfield
- trimethyl
- glycine
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Abstract
The invention relates to chemical synthesis for salicylic betaine salt. The product can match with other drugs to external use or take orally as aqua, soft plaster, capsule or injection, which has wide application in reducing fever, easing pain, anti platelet aggregation, anti senile cataract, protecting normal cell, anti atherosclerosis and other functions.
Description
Technical field the present invention relates to the trimethyl-glycine salicylate analgesic, analgesia, anti-inflammatory, platelet aggregation-against, antimycotic, atherosclerosis, the protection normal cell of chemosynthesis and it, the field that prevents effects such as the muddy and protection hepatic and renal function of crystal fibre.
The background technology cardiac and cerebral vascular diseases becomes the human primary cause of the death day by day.These diseases are the overwhelming majority grow up on atherosclerotic basis, therefore how to develop and safeguard cardiovascular normal function, suppress atherosclerotic protective foods and medicine, and this has become problem anxious to be solved.
1, feed to contain the trimethyl-glycine feed for the rat of high sterol mass formed by blood stasis alcoholic hepatitis for a long time, can make homocysteine (homocysteinemia in the blood, Hey) content descends, and hyperhomocysteinemiainjury (hyperhomocysteinemia, HHcy) be the independent risk factor of cardiovascular and cerebrovascular diseases and senile dementia, thereby trimethyl-glycine can suppress progression of atherosclerosis and treatment senile dementia (Cheng Ji, Neil Kaplowitz. homocysteine mass formed by blood stasis, er stress and alcoholic liver injury, Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury.World J Gastroenterol 2004; 10 (12): 1699-1708).
2, a large amount of studies show that; trimethyl-glycine can be by strengthening the expression of heme oxidase; promote that endogenic CO produces in the liver cell; the CO of lower concentration has the protection cell and suppresses apoptotic effect; promote the activity of the sweet cyclase of acid of bird, c-GMP concentration is increased, activate mitogen activated protein kinase (MAPK); suppress apoptotic pathways and promote the synthetic of the interior sweet methionine(Met) of S-gland of liver, the activity of arrestin kinase c (PKC) is protected cell.Nearest studies show that; in bile acide inductive liver injury animals model, trimethyl-glycine can suppress cytochrome C and be released into cytoplasm from plastosome by stablizing mitochondrial membrane; thereby suppress the activation of Caspase-9, finally suppress apoptosis and protection liver cell.
3, trimethyl-glycine is a kind of chemosmosis agent, chemistry betaine by name, and molecular formula is (CH
3)
3NCH
2COOH.Cl/NO
3, molecular weight is 118+35.5/62, its content in plant, vegetables, herbal medicine is abundant, but also chemosynthesis.It generally is used for makeup as a kind of surfactant, toothpaste or high-grade clean-out system.The people is also arranged as Italy's (the country one belongs to's pharmacopeia) abroad, the U.S. is used for the treatment of the nonspecific hepatitis that alcoholic hepatitis and a variety of causes cause, liver cirrhosis (Barak, et al.United States Patent, 5,428,063), and belong to the patent of the nineties in 20th century, and do not come into one's own as yet at present at home (Chinese patent retrieval and literature search).
4, acetysalicylic various effect is well-known.In application process, many new effects constantly are found, and the discovered in recent years acetylsalicylic acid can be used for cataractous inhibition (Wang Xiangqun, Deng, the acetylsalicylic acid control is from the present situation and the prospect of cataract or glaucoma research, foreign medical science ophthalmology fascicle, 1997,21 (4): 211-216).Itself has physiological functions such as antipyretic-antalgic Whitfield's ointment, but it is bigger to GI irritation, now is only limited to external application.In order to reduce its side effect, improve curative effect, just studying salicyclic acid derivatives or its prodrug preparation (Piao Longqia both at home and abroad, Deng, the preparation of two Whitfield's ointment Methionins and analgesic activity thereof, number reason medicine and pharmacology magazine, 1997,10 (4): 341), but the salicylic development of trimethyl-glycine does not appear in the newspapers as yet.Cataract is human common illness in eye, also is the one of the main reasons of blinding, clinical metabolic, the broad variety such as traumatic, senile, congenital of being divided into.The cataractous main medicine of treatment has gsh at present, contains the medicine of SH base, aldose reductase inhibitor etc., but result of treatment is all not exclusively satisfied.
In view of hyperhomocysteinemiainjury (hyperhomocysteinemia, HHcy) be the independent risk factor of cardiovascular and cerebrovascular diseases and senile dementia, it also is the important pathogenic factors of fatty liver and alcoholic liver, diabetes and fatty liver finally can cause cataract, and trimethyl-glycine can reduce the homocysteine in blood and the liver, therefore the inventor imagines trimethyl-glycine and can be used for treating metabolic and senile cataract, prove through animal experiment, the treatment of trimethyl-glycine Whitfield's ointment is respond well by the cataract that semi-lactosi causes, has therefore proposed the present invention and pharmacotoxicological effect thereof.
Summary of the invention the invention provides analgesic, the analgesia, anti-inflammatory, platelet aggregation-against of the chemical synthesis process of trimethyl-glycine salicylate and derivative and it, antimycotic, atherosclerosis, protection normal cell; prevent effects such as crystal fibre muddiness and protection hepatic and renal function; but also oral administration of external application clinically; can be used for analgesic, analgesia, anti-inflammatory, platelet aggregation-against, antimycotic; anti-cataract, anti-hepatitis, ephritis and cardiovascular and cerebrovascular diseases patient's assisting therapy.
Get 138.12g Whitfield's ointment (homemade), add an amount of dehydrated alcohol, add water-soluble 117g trimethyl-glycine (import packing) slowly under stirring then, react completely, concentrate, separate out crystallization to all dissolvings.The dry 252g trimethyl-glycine salicylate that gets, productive rate is 99%.Its reaction formula is as follows:
The trimethyl-glycine salicylate that this paper adopts Whitfield's ointment and trimethyl-glycine to make compares with Whitfield's ointment, favorable solubility in water, and the mouthfeel flavor is sweet, and does not have salicylic puckery and tart flavour, does not also have the bitter taste of trimethyl-glycine, is applicable to oral and intramuscular injection.
This paper adopt trimethyl-glycine salicylate that Whitfield's ointment and trimethyl-glycine make and with acetylsalicylic acid relatively.Pharmacological evaluation shows.Its analgesic effect is apparently higher than acetylsalicylic acid, and toxic action then obviously reduces.
The trimethyl-glycine salicylate that this paper adopts Whitfield's ointment and trimethyl-glycine to make; the effects such as, analgesia analgesic, anti-inflammatory, platelet aggregation-against, antimycotic, protection normal cell except can be used for; also can be used for atherosclerosis, prevent the assisting therapy of crystal fibre muddiness and senile dementia etc.
The trimethyl-glycine salicylate that this paper adopts Whitfield's ointment and trimethyl-glycine to make can also be used for the treatment of acute hepatitis and hepatic fibrosis.
According to the trimethyl-glycine salicylate such use, it can use with other preparation or compatibility of drugs, also can be used as mixed preparation and uses.Can be single or be mixed and made into capsule, oral liquid, granule with other medicines, tablet or injection can oral or intravenous injections.
The present invention is described further below in conjunction with embodiment for embodiment
Embodiment one, gets 138.12g Whitfield's ointment (homemade), adds an amount of dehydrated alcohol to all dissolvings, stirs down to add water-soluble 117g trimethyl-glycine (import packing), reacts completely, concentrates, and separates out crystallization.The dry 253g trimethyl-glycine salicylate that gets, productive rate is 98%.Its reaction formula is as follows:
Embodiment two, get the 117g trimethyl-glycine, use an amount of dissolved in distilled water, add the 138.12g Whitfield's ointment, are stirred to and react completely, are heated to 50 ℃, and concentrating under reduced pressure is separated out crystallization.The dry 254g trimethyl-glycine salicylate that gets, productive rate is 99.9%.Its reaction formula is as follows:
Embodiment three, the trimethyl-glycine salicylate acute toxicity test
According to pre-test result, trimethyl-glycine Whitfield's ointment maximal dose group is set to 2000mg/kg, and all the other each groups are successively decreased with 0.8 geometric progression, are followed successively by 1600mg/kg, 1280mg/kg, 1024mg/kg, 800mg/kg, 640mg/kg, 500mg/kg, 400mg/kg.Gastric infusion, the administration volume is 0.5ml/20g, and the soup compound concentration is respectively 80mg/ml, 64mg/ml, 50mg/ml, 40mg/ml, 32mg/ml, 25mg/ml, 20mg/ml.
Choosing body weight is 80 of 19-21g mouse, is divided into 8 groups at random, and 10 every group, male and female half and half by set dosage intraperitoneal injection, begin after the administration to observe immediately.Animal activity reduces after 5 minutes, has animal that convulsions is arranged, and does not see the 2-14 days interior no animal deads that animal dead is observed later in 2 days, and animal is observed to put to death after 14 days and dissects each organ no abnormality seen of visual inspection.
Test-results shows, intraperitoneal injection of mice trimethyl-glycine Whitfield's ointment LD
50Adopt current dose not measure
Embodiment four, and the trimethyl-glycine salicylate is to rat alcoholic fatty liver and atherosclerotic protection and therapeutic action
One, laboratory animal
Adopt health, sexual maturity, 42 of the SD rats of first quality standard (available from No.1 Military Medical Univ.'s Experimental Animal Center), male and female half and half, body weight 180-200g divides cage to feed.
Two, experimental technique
1. chronic alcoholic fatty liver modeling:
Each all gives 56 liquor of spending every day during organizing rat experiment, on average is added in the tap water with 4ml/100ml and the high lipid food nursing, and the prescription reference literature is also improved, and adopts 88% basal feed, 10% lard, 2% cholesterol.
2. experimental program and grouping.
52 of healthy SD rats are divided into 3 groups at random, 10 of A groups, and as normal group, normal diet and water; B organizes 12 as the alcoholic fatty liver group; 30 of C groups as experimental group, are male and female half and half.B group is killed mouse respectively at experiment back 2,4 or 8W and is got liver, aorta and blood, does pathological section and Serological testing, observes the formation situation of model, the modeling success back alcohol of stopping using.Control group and experimental group continue to raise with high lipid food, and control group is freely drunk water with common; Experiment component is: be divided into three groups, and high dose group, 10, by 2% trimethyl-glycine Whitfield's ointment administration; Middle dosage group, 10, by 1% trimethyl-glycine Whitfield's ointment administration; Low dose group, goes out by 0.5% trimethyl-glycine Whitfield's ointment administration falling rocks by 10; All add in the drinking-water and freely drink.
3. sample preparations
Control rats is got 1 rat at random behind back 4wk and the 8wk and is put to death with the femoral artery depletion method respectively at handling.Get blood and do every Serological testing, get liver and artery after the execution immediately, the back of weighing is fixed with formalin solution, does the routine paraffin wax stripping and slicing, HE dyeing and picric acid sky wolf red colouring, microscopic examination.As treat success, and then put to death whole rats, do the routine paraffin wax stripping and slicing, HE dyeing and picric acid sky wolf red colouring, microscopic examination.
4. detection content
(1) generalized case: the mental status in the animal rearing process, active situation, hair luster, appetite, stool and urine situation etc.Weigh/week.
(2) liver specimens is seen substantially: weigh and observe size, color and luster, quality, tangent plane situation of liver etc.
Liver index=liver weight/body weight
(3) get left lobe of liver 0.2g, make 10% liver homogenate under 4 ℃, use chloroform: methyl alcohol (2: 1v/v) liquid extracting lipid, promptly the supernatant soluble part is measured by the test kit operation steps with enzyme process, and TG represents intrahepatic fat content, and unit represents with the mg/g liver.
(4) serology detects index: gpt (ALT), triglyceride (TG), cholesterol (CHO).
(5) the liver tissues of rats paraffin section is made HE dyeing and picric acid sky wolf red colouring respectively, and light microscopic detects.
5, statistical procedures: measurement data is with (x ± s) expression uses SPSS10.0 software, and measurement data relatively adopts variance analysis between each group, and ranked data are checked with Ridit, and P＜0.05 is that there were significant differences.
Three, result
1, generalized case: at the 9th weekend, the normal rats hair color is bright and new, and it is good to ingest, quick active; Control rats hair color dimness, poor appetite, slow lazyness is moving; Experiment is respectively organized the rat hair color near normal, and appetite is normal, and reaction is quick.
2, liver sample observation substantially: naked eyes sight normal rats liver color and luster is dark red, and tunicle is smooth, clear-cut margin, and tangent plane is moistening; The control group liver volume obviously increases, and whole liver is milk yellow, and sees focal yellow-white sex change kitchen range, the coating anxiety, and the edge circle is blunt, and tangent plane is greasy.Experimental group liver outward appearance is near normal, and color and luster is ruddy, and tunicle is more smooth, and the edge is sharper keen, and tangent plane is more moistening.
3, pathological observation: om observation normal hepatocytes leaflet structure is clear, cell rope marshalling, and sinus hepaticus is normal, and the liver cell kytoplasm is red to be dyed, and does not see cavity or lipoid degeneration, and nuclear structure is clear; Control group shows that hepatic tissue is destructurized, the leaflet boundary is unclear, the disorder of cell rope, and most of sinus hepaticus disappears, the extensive steatosis of liver cell, be the bulla sample more and change, begun to spread, extend to periphery gradually by central Venule, cell volume increases, the fat karyon that attenuates among the born of the same parents is dripped by fat and presses to a side, become seal to guard against sample and change, most of cell cytoplasm is loose, understain, part of hepatocytes disintegration necrosis.It is better that lipid-lowering effect is respectively organized in experiment, no obvious cavity and loose in the liver cell, part of hepatocytes is slight cloudy swelling, fat drips calm less, the liver lobule clear in structure, and the cell rope is arranged more neat, but fat drips calm more, slightly heavy around the sinus hepaticus mild stenosis, central vein than leaflet periphery denaturation degrees, the karyon clear in structure.
5, the trimethyl-glycine Whitfield's ointment is to the influence (table 1) of experimental rat liver exponential sum intrahepatic fat.The result shows that the trimethyl-glycine Whitfield's ointment can obviously reduce lipid content in the liver, and is dose-dependently.
Table 1 trimethyl-glycine Whitfield's ointment to the influence of experimental rat liver index (LI) and intrahepatic fat (x ± s, n=10).
| Liver index (LI) | TG in the liver (mg/g tissue) | |
| Dosage group low dose group in the normal group control group trimethyl-glycine Whitfield's ointment group high dose group | 2.95±0.48 4.16±0.79 3.06±0.88 ** 3.43±0.92 ** 3.81±1.03 | 21.33±5.09 45.06±14.71 23.24±7.02 ** 28.53±5.26 ** 34.67±9.03 * |
P＜0.01, with normal group relatively;
*P＜0.05,
*P＜0.01, with control group relatively.
6, the trimethyl-glycine Whitfield's ointment is to experimental rat ALT, TG, CHO influences (table 2), table 2 shows: but the trimethyl-glycine Whitfield's ointment can obviously reduce the activity concentration of ALT and CHO in the blood, and be dose-dependently, but serum TG concentration rises in the trimethyl-glycine Whitfield's ointment, may promote that fat shifts relevant in the liver outside liver with the trimethyl-glycine Whitfield's ointment.
Table 2 trimethyl-glycine Whitfield's ointment is to mice serum ALT, TG, CHO (x ± s, influence n=10)
| ALT | TG(mmol/L) | CHO(mmol/ L) | |
| Dosage group low dose group in the normal group control group experimental group high dose group | 38.46±2.05 109.23±6.33 42.57±5.78 ** 52.62±6.72 ** 78.11±5.51 * | 1.46±0.38 3.16±0.57 3.86±0.78 * 3.43±0.42 3.21±0.43 | 2.55±0.48 4.07±0.79 2.67±0.67 ** 3.03±0.82 ** 3.21±1.10 * |
P＜0.01, with normal group relatively;
*P＜0.05,
*P＜0.01, with control group relatively.
7, the trimethyl-glycine Whitfield's ointment is to the influence (table 3) of fat in the hepatic tissue.Control group liver fat area and total area ratio percentage ratio obviously increase, and trimethyl-glycine Whitfield's ointment group is compared obvious decline with control group, have significant difference (P＜001) to see Table 3.
Table 3 trimethyl-glycine Whitfield's ointment is to fatty liver rats'liver fat area percent (x ± s, influence n=10)
| The metering total area (mm 2/ liver) | The fat area percent | |
| Dosage group low dose group in the normal group control group trimethyl-glycine Whitfield's ointment group high dose group | 6120.6±2816.7 8120.6±2816.7 6406.5±1106.5 6511.6±827.7 7016.7±832.3 | 3.1±1.3 32.3±10.7 8.81±8.1 ** 12.08±6.7 ** 19.08±11.6 * |
P＜0.01, with normal group relatively;
*P＜0.05,
*P＜0.01, with control group relatively.
Four, the result shows: the trimethyl-glycine Whitfield's ointment can obviously reduce lipopexia in the liver, mouse chronic hepatic injury and opposing liver fatization that protection is caused by alcohol and high fat diet.
Embodiment five, and the trimethyl-glycine Whitfield's ointment is to the influence of subcutaneous injection D-semi-lactosi rat cataract animal model
One, materials and methods
1, laboratory animal Wistar rat (No.1 Military Medical Univ.'s Experimental Animal Center provides), 40, male and female half and half.
2, medicine and reagent semi-lactosi (AR, Shanghai biochemical reagents two factories) are made into 50% injection liquid, and use conventional sterilization back; Trimethyl-glycine salicylate (AR, self-control); Compound takes off product acid amides collyrium (Beijing Double-Crane Modern Medicine Technologies Limited Liability Company), uses for expanding pupil before the microscopy.
3, the foundation of rat D-galactose cataract model: 3w age (21d age) Wistar rat, mean body weight 25 ± 5g, the slit lamp examination lens is transparent behind mydriasis.The equal routine disinfection of animal in nape portion subcutaneous injection 50% semi-lactosi (30ml/kg/d), is equivalent to semi-lactosi 15g/kg/d); Every day 1 time, 30d continuously.
4, experiment grouping: control group, 10; 1% Whitfield's ointment group, 10; 2% trimethyl-glycine Whitfield's ointment group, 10; 0.5% trimethyl-glycine Whitfield's ointment group, 10.Control animals is freely drunk water, and Whitfield's ointment and trimethyl-glycine Whitfield's ointment join in the drinking-water to be drunk.Each treated animal in 7,14,21,30d respectively with compound mydriacyl mydriasis after, with the dynamic change of slit lamp observation crystalline, and by following standard the cataract that takes place is carried out classification and comparison: the I level: lens does not have muddiness; The II level: lens is slightly muddy, and cavity appears in periphery; The III level: lens moderate muddiness, peripheral cavity is expanded to the center, and vaporific muddiness appears in centronucleus; The IV level: lens height muddiness, cavity expand to the nuclear district, and the vaporific muddiness of centronucleus increases the weight of; V level: lens nucleus muddiness, cataract maturation.
5, statistical treatment: data are all used x between each group
2Check.
Two, result:
The muddy situation of each phase crystal of experimental group and control group is (table 4) relatively
Table 4 is respectively organized the comparison (n=20) of rat crystal pathological change behind the injection different time
| 7d | 14d | 21d | 30d | |||||||||||
| I | II | I | II | III | IV | I | II | III | IV | II | III | IV | V | |
| Control group Whitfield's ointment group trimethyl-glycine Whitfield's ointment high dose group low dose group | 2 9 6 8 | 18 - - - | - 6 12 10 | - 10 8 10 | 20 4 - - | - - - - | - 4 10 6 | - 2 8 8 | 2 12 2 3 | 18 2 - 1 | - 4 12 10 | - 2 6 5 | 2 2 2 3 | 18 10 2 2 |
The result shows that Whitfield's ointment can obviously weaken the forming process (with control group significant difference relatively arranged) of semi-lactosi to rat cataract, and to slow down cataractous formation effect especially obvious and trimethyl-glycine is salicylic.
Three, conclusion: the trimethyl-glycine salicylate can obviously slow down experimental cataractous formation.
Embodiment six, the preparation of trimethyl-glycine salicylate (the bright capsule of eye)
Trimethyl-glycine salicylate: 1500g
Auxiliary material (Zinic stearas/Magnesium Stearate, Microcrystalline Cellulose etc.) 500g balanced mix is even, encapsulated 10000.Also can be pressed into tablet.
Usage: 0.2-0.6g/ time, three times/day.Purposes: be used for the prevention and the treatment of senile cataract.
Embodiment seven, the preparation of trimethyl-glycine salicylate eye ointment or collyrium.
The trimethyl-glycine Whitfield's ointment of 0.1-3%, preferred 0.5%, add relevant auxiliary materials, accents pH is 6.5-7.5, branch 10-50ml flexible pipe or Glass tubing.
Usage: external application is used for the treatment of senile cataract.
Embodiment eight, the preparation of compound betaine salicylate (the bright capsule of compound eye)
Trimethyl-glycine salicylate: 1500g
Vitamin-E 0-500g, preferred 50g;
Vitamin A 0-10g, preferred 3g;
VitaminB10-20mg, preferred 3mg;
Wei ShengsuB2 0-20g, preferred 4g;
Vitamin B6 0-40g, preferred 5g;
Vitamin B12 0-200mg, preferred 30mg;
Vitamins C 0-2000g, preferred 300g;
Folic acid 0-20g, preferred 2g;
Vitamin H, 0-2000mg, preferred 200mg;
Pantothenic acid, 0-200g, preferred 20g;
Nicotinic acid, 0-2000g, preferred 100g;
Various trace elements, auxiliary material (Zinic stearas/Magnesium Stearate, Microcrystalline Cellulose etc.) 100g balanced mix is even, encapsulated 10000.Also can be made into tablet.
Usage: 0.2-0.6g/ time, three times/day.Purposes: be used for the prevention and the treatment of senile cataract.
Embodiment nine, the preparation of compound betaine salicylate (compound heart and brain curing capsule)
Trimethyl-glycine salicylate: 1500g
Arginine 10-5000g, preferred 500g;
Vitamin-E 0-500g, preferred 50g;
Vitamin A 0-10g, preferred 3g;
VITMAIN B1 0-20mg, preferred 3mg;
Wei ShengsuB2 0-20g, preferred 4g;
Vitamin B6 0-40g, preferred 5g;
Vitamin B12 0-200mg, preferred 30mg;
Vitamins C 0-2000g, preferred 300g;
Folic acid 0-20g, preferred 2g;
Vitamin H, 0-2000mg, preferred 200mg;
Pantothenic acid, 0-200g, preferred 20g;
Nicotinic acid, 0-2000g, preferred 100g;
Various trace elements, auxiliary material (Zinic stearas/Magnesium Stearate, Microcrystalline Cellulose etc.) 500g balanced mix is even, encapsulated 10000.Also can be pressed into tablet.
Usage: 0.8-0.9g/ time, three times/day.Purposes: be used for the prevention and the treatment of cardiovascular and cerebrovascular diseases, atherosclerosis, senile dementia.
Claims (9)
1, is applicable to analgesic, analgesia, anti-inflammatory, platelet aggregation-against, antimycotic, anti-senile dementia; anti-ageing year cataract, atherosclerosis, protection normal cell; with the trimethyl-glycine Whitfield's ointment and corresponding isomer and the preparation method that protect effects such as hepatic and renal function; it is characterized in that: garden beet alkali and Whitfield's ointment salify, and represent with following structural:
2, trimethyl-glycine Whitfield's ointment according to claim 1 and corresponding isomer and preparation method, it is characterized in that: described preparation method is as follows: an amount of dissolved in distilled water of 1.17g trimethyl-glycine, slowly add the 1.382g Whitfield's ointment, stirring reaction liquid is to clarification, air-dry, lyophilize or vacuum-drying below 60 ℃.
3, preparation method according to claim 1 and 2 is characterized in that: the mol ratio of described Whitfield's ointment and trimethyl-glycine is arbitrary ratio, preferred 1: 2 or 1: 1.
4, preparation method according to claim 1 and 2 is characterized in that: the drying means of described Whitfield's ointment-beet alkali salt, can take any physical method below 60 ℃.
5, preparation method according to claim 1 and 2 is characterized in that: described trimethyl-glycine comprises formyl radical, ethanoyl, propionyl and butyryl radicals-trimethyl-glycine, or arbitrary biological trimethyl-glycine.
6, preparation method according to claim 1 and 2 is characterized in that: described Whitfield's ointment comprises Whitfield's ointment or salicylic resin such as acetylsalicylic acid, or greasiness acyl Whitfield's ointment, and also available arbitrary non-steroid antiphlogiston (as Ibuprofen BP/EP) substitutes Whitfield's ointment.
7, trimethyl-glycine Whitfield's ointment according to claim 1 and 2 and corresponding isomer is characterized in that: they have common bigcatkin willow acidolysis heat, analgesia, anti-inflammatory, platelet aggregation-against, effect such as antimycotic.And has anti-cataract crystal fibre muddiness, protection hepatic and renal function, protection normal cell, effects such as arteriosclerosis patch formation.
8, trimethyl-glycine Whitfield's ointment according to claim 1 and 2 and corresponding isomer; it is characterized in that: they have the acute, chronic hepatitis hepatocyte protection; the protection of acute and chronic nephritis uriniferous tubules, senile dementia, effects such as cardiovascular and cerebrovascular diseases and senile cataract prevention, treatment.
9, Whitfield's ointment beet alkali salt according to claim 1 and 2 and corresponding isomer is characterized in that: Whitfield's ointment beet alkali salt of the present invention can use with other preparation or compatibility of drugs, also can be used as mixed preparation and uses.Can external application or for oral administration, can be single or be mixed and made into external application aqua, finish or creme, ointment medicine or the water-sol with other medicines, also can make capsule, oral liquid, granule, tablet or injection can oral or intravenous injections.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110294683A (en) * | 2019-05-20 | 2019-10-01 | 深圳市萱嘉生物科技有限公司 | A kind of glycine betaine phenolic acid ion salt and the preparation method and application thereof technical field |
| CN110236974A (en) * | 2019-06-14 | 2019-09-17 | 珠海萱嘉君行健康产业发展有限公司 | A kind of toner and preparation method thereof containing glycine betaine salicylic acid ionic liquid |
| CN112409198A (en) * | 2019-08-23 | 2021-02-26 | 衢州市展宏生物科技有限公司 | Betaine salicylate and preparation method thereof |
| CN113620827A (en) * | 2021-07-02 | 2021-11-09 | 深圳市萱嘉生物科技有限公司 | Betaine salicylic acid eutectic crystal and preparation method and application thereof |
| WO2023274401A1 (en) * | 2021-07-02 | 2023-01-05 | 深圳市萱嘉生物科技有限公司 | Betaine salicylic acid eutectic, preparation method therefor, and application thereof |
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