CN1108528A - Biologically actie dermatological treatment - Google Patents

Abstract

The present invention relates to a synergistic compound which contains methylsulfonyl methane and a kind of sulfur-bearing amino acid. Besides, said invention also relates to its application in preparation and therapeutic method for protecting skin and improving skin opsonization.

Description

Biologically actie dermatological treatment

The present invention relates to a kind of treatment dermatosis and pharmaceutical composition in disorder and that improve skin condition of being applicable to.

Since skin to environmental pollutants, the susceptibility of stimulus object and toxic reagent and because skin surface is long-pending big, be the regular incidence position of degeneration, inflammation, endocrine, metabolism or formation tumor so skin is various diseases and disorder.Although many dermal agents are arranged on the market, these medicaments are difficult to the media of opposing skin injury or disease, or strengthen the repair ability of skin after damage or disease, or resist this recurrence in disorder or prevent that its development is to keep the integrity of skin.Moreover present getable many medicine for treatment modes all have limitation to patient's selection or application.Therefore, the objective of the invention is to introduce a kind of synergistic pharmaceutical combination, said composition can not only overcome these limitation, and can also effectively resist the media that causes dermatosis or damage, strengthen the repair ability of suffered any damage or damage, and, keep the integrity of skin by strengthening disease or the resistance that recurs in disorder that the skin opposing was treated.

The invention provides a kind of synergistic pharmaceutical combination, said composition contain the aminoacid of methyl sulfonyl methane and a kind of sulfur-bearing such as cysteine, cystine, cysteamine, methionine carboxyl esterification with S-methylmethionine sulfonium derivant.This carboxyl is preferably had the low alkyl group such as the methyl-esterified of 1-6 carbon atom.S-methyl substituted ternary sulfonium derivant such as bromination, iodate and the chlorination methionine methyl sulfonium that also can contain methionine.

It should be noted that more above-mentioned at least chemical compounds have one or more optical activities center, especially in the aminoacid situation of substituted-amino and carboxyl carbon.Therefore, in order to disarm suspicion, two independent isomers can observing that the present invention extends such as D-and L-isomer and enantiomer, and when having two or more optical activities center, diastereomer and mixture of isomers also comprise the DL mixture of racemization.

Be surprised to find that, methyl sulfonyl methane can change degeneration and the ageing process that skin occurs, the treatment various diseases is inflammation, metabolism, endocrine or wound such as wound and routed trace, and can make skin avoid these diseases and recurrence in disorder by postponing its plysiochemical character, thereby strengthen skin causes damage to noxious substance resistance; Meanwhile, especially wonderful discovery is added sulfur-containing amino acid and can be promoted its treatment benefit with cooperative mode.Each active component total contribution that this effect relates to is lower than the effect that these active component combine and can reach.Also can be observed said composition and have the favourable character that adheres to skin, thereby prolonged and the contacting of area for treatment, improve therapeutic efficiency.Have following effect with the in vitro tests proof present composition in the body:

1. eliminate the deutero-free radical of oxygen, this free radical is a cytotoxic agent, with tissue damage and wound congener, can weaken the process of curing and repairing in addition.

2. cytoprotection relates to the physiology-chemical property that postpones biological tissue, therefore can strengthen the resistance to poisonous stimulus object.

3. giving of biosynthesis and sulfur, its influence strengthen repairs and cures.

As long as do not limit the scope of the invention, can think one or more beneficial effects that on either large or small degree, cause the present composition to have of these effects.

The present composition is applied on the skin to improve its conditioning, can adopts many modes, comprising:

A. improve the order of severity of the degeneration variation that has occurred.

B. prevent the development of this variation.

C. by postponing its plysiochemical character, improve the resistance of skin, can prevent the illeffects of environmental stimulus thing, pollutant and toxic reagent thus damage.

D. have effective sun-proof effect, thereby prevent that ultraviolet from making skin that deposition degeneration and premature aging take place.Can strengthen the susceptibility that transforms harmful in addition.

E. strengthen healing ability to inflammation, E﹠M disorder.

F. strengthen the healing of wound, ulcer, crackle and sinus tract, also can strengthen dermatoplastic processing and healing.

The improvement of skin condition aspect also can comprise maintenance skin vitality, smooth, firm and tissue.

Advantageously, in order further to strengthen the effectiveness of said composition in skin, also can contain vasodilator substance such as menthol.In addition, have been noted that and in the present composition, mix vitamin A and E can improve the effect of treatment.

In addition, the invention provides a kind ofly contain methyl sulfonyl methane and sulfur-containing amino acid, with the pharmaceutical carrier uniform mixing, be applicable to the Pharmaceutical composition that improves skin condition.

On the other hand, the invention provides a kind of mixed uniformly topical preparation of methyl sulfonyl methane and sulfur-containing amino acid and pharmaceutical carrier of containing, this carrier to biological tissue should not be deleterious or with any composition of said preparation can not be compatible.Because some people more can not be fused into one with any composition of said preparation than other people's skin.

The carrier that is suitable for is well known in the prior art, at all in its general publication, as British National Formulary and British Pharmacopoeia(British National Formulary and British Pharmacopoeia) in be described.These carriers comprise ointment and cream substrate, washing liquid, paste, gel, spray, aerosol and bath oil.Ointment and cream can contain oiliness suction colloidal clays, thickening agent such as tragacanth gum or sodium alginate and other medicinal auxiliary element, and as lubricant, antiseptic, buffer agent and antioxidant, these all are useful in described preparation.Usually cream preparation is best, because be the most receptible for most of user.A kind of specially suitable substrate is the substrate with the polyethyleneglycol cetyl ether, comprise for example 30%W/V polyethyleneglycol cetyl ether emulsifying ointment (30%W/V polyethyleneglycol cetyl ether emulsifing wax, the 20%W/V liquid paraffin, 50% white soft paraffin) newly boil with refrigerative pure water in, this water contains for example 0.1%W/V chlorocresol or 0.08%W/V propyl hydroxy benzoate, the benzylalcohol of 0.15%W/V methyl hydroxybenzoate and 1.5%W/V.

Its various active component contents of topical preparation of the present invention are at least 0.5%W/W, are preferably 1-20%W/W, are preferably 1-10%, for example 5% methyl sulfonyl methane and 2% cysteine or methionine.When containing menthol, use amount is 1-20%W/W usually, is preferably 1-5%W/W.

In addition, the present invention can mouthful absorption administration or parenteral, especially intravenous injection in suitable carrier.

When being used for oral administration, each composition of the present invention and any additional material, the form that exists can be water or syrupy potus, capsule, sachet, bolus or tablet, as the suspension in water or oily solution or suspension or the syrup, the alternative suspending agent-containing of this suspension or oil-in-water or water-in-oil emulsion.

Comprise oral route, the present composition can be to use in alcoholic solution, wine or the medicated beer at the beverage of alcohol.The beverage of non-pure type also can be used as the carrier of pro ore of the present invention.In addition, compositions of the present invention can also be added in fruice, the mineral water (carbonating or not carbonating), but also can add in the soft drink of form of ownership.

The present composition can directly be transported in the lung by smog, and in this, they can be used as powder or solution and are added in the Nicotiana tabacum L. or are added in the tobacco shred of medicated cigarette, cigar and tobacco pipe.The present composition also can make the powder of solution or medicated cigarette filtrate or add the very little compartment that transports in the medicated cigarette.This interlayer also can contain and be the granular present composition.Volatilization when contacting with smog, thus its active component transported by the smog carrier band.

Said preparation also can contain that want or necessary spice, sweeting agent, antiseptic, thickening agent or emulsifying agent.

Tablet also can contain with binding agent, lubricant, inert diluent or surfactant or dispersant be powder or granular composition of the present invention and additional arbitrarily material.

During for parenteral, the present composition and any additional material all can be present in the antiseptic solution or suspension of aqueous or oiliness carrier, wherein also can contain the material of antiseptic, antioxidant and suitable and isoosmotic solution of receiver's blood or suspension.Said preparation can easily be sealed in the container with unit dose or many multiple doses.

Be used for oral or during parenteral, the present composition preferably exists with unit dose or many multiple doses form of solution, suspension or emulsion, its concentration is 0.5%-20%W/V, better is 2-5%W/V.When existing with unit dosage form, its every kind active component content of per unit dosage is preferably 100-500mg.This dosage can be given one or many every day, preferably is spaced apart 2-8 hour, and preferably per 6 hours once.Advantageously, the composition of present composition administration in slow release or self-dalay release vehicle.Such various suitable carrier is that prior art is known.

When being used for topical therapeutic, described compositions can be applied on the skin, be coated on the whole area of desire treatment every day 1-3 time, and massaged about 3-5 minute.If will make the injury repairing of any skin, application is at dusk spent the night.New in order to be coated with one deck, there is no need to wash off former application, even wash off also as long as carry out simply with warm water.

Further preferred feature of the present invention and advantage will come into plain view by the following example, provide the purpose of embodiment only to be explanation.

Embodiment 1: be used for the treatment of the preparation of the topical formulations of skin

A. methyl sulfonyl methane 5g

DL-cysteine hydrochlorate 2g

Polyethyleneglycol cetyl ether ' A ' adds to 100g

B. methyl sulfonyl methane 5g

DL-cysteine hydrochlorate 2g

Menthol crystal 1g

Polyethyleneglycol cetyl ether ' A ' adds to 100g

C. methyl sulfonyl methane 5g

Methyl chloride methionine sulfur 2g

Polyethyleneglycol cetyl ether ' A ' adds to 100g

D. methyl sulfonyl methane 5g

Methyl chloride methionine sulfur 2g

Menthol crystal 1g

Polyethyleneglycol cetyl ether ' A ' adds to 100g

These preparations are to prepare in the medium of 25 ℃ of temperature.In glass or rustless steel container, the methyl sulfonyl methane of 5g is mixed with cysteine hydrochloride or the methyl chloride methionine sulfur of 2g.The Powdered menthol that adds 1g then.The polyethyleneglycol cetyl ether is added to 100g, whole compositions was mixed 10 minutes.And then product put into before the opaque airtight glass container, it was left standstill 15 minutes at least, and store down for 26 ℃ in optimum temperature, preferably be not higher than this temperature, be not placed on the periods of direct sunlight place.After the preparation, these preparations just use after 24 hours at least, and long term exposure directly is not exposed under the sunlight in air yet.

Embodiment 2: the use of local cream preparation

Embodiment 1 described cream can apply for several times in one day, and the application that is coated with is at dusk spent the night, and used the warm water flush away that adds soap or do not add soap second day morning.Look each case situation treatment a couple of days or several months.Usually, during for the protection purpose, preparation is coated on the skin part of desire protection, once a day,, not be exposed under environmental stimulus thing or the sunlight before this as face and arm.As when being therapeutic purposes, according to the state of an illness control coating time to be treated, as dermatitis 5-10 days (unless cause by cirso-, treatment will be extended down to for 4 weeks), wound healing 2-3 week, swelling ulcer 12-16 week, in these cases, apply 2-3 every day, and best interval is 8 hours.Successfully continuing treatment after the treatment, or keeping skin conditioning, needing once a day that specific part coating at skin continues the several months, several years even infinitely.

Embodiment 3: the detailed mensuration of compositions

A. be in one group respectively the organizing 20 Sprague-Dawley Mus of getting two kinds of sexes arbitrarily, the heavy 200-290g of Mus detects the influence to Mus gastric mucosa acute injury of methyl sulfonyl methane and cysteine.The solution for preparing cysteine or methyl sulfonyl methane with redistilled water.Use the 6FG charge pipe to instil by gastrostome under a small amount of etherization, all medicines are all delivered in the stomach through tube feed, the animal fasting is after 24 hours, and the cysteine of 1ml and/or methyl sulfonyl methane or redistilled water are splashed in the stomach.Tube feed 1ml40% ethanol or redistilled water after 1 hour.With excess dose ether kill animals, collect its gastric acid secretion thing after 2 hours, and with 0.1M NaOH titration to pH7, analysis H ⁺Output, detect their stomach, check that the degree of the acute gastric mucosal lesion that alcohol brings out (is used mm ²Surface area is represented the standard error of each cell mean ± meansigma methods, SEM).Carry out following observation:

The therapy animal shows damage damaged area mm ²

(n=20) the incidence rate % of Shanging (meansigma methods ± SEM)

Distilled water+distilled water 0% 0

Distilled water+ethanol 100% 40 ± 1.2

0.5%MSM+ ethanol 80% 31.7 ± 1.4

1%MSM+ ethanol 70% 25.1 ± 0.9

5%MSM+ ethanol 60% 18.3 ± 1.1

10%MSM+ ethanol 60% 17.9 ± 1.5

20%MSM+ ethanol 60% 19.1 ± 1.2

0.5% cysteine+ethanol 90% 32.3 ± 1.6

1% cysteine+ethanol 70% 25.1 ± 1.1

5% cysteine+ethanol 50% 16.2 ± 0.8

10% cysteine+ethanol 50% 16.1 ± 0.9

20% cysteine+ethanol 50% 15.9 ± 1.2

0.5%MSM & 50% 12.3±1.4

0.5% cysteine+ethanol

1%MSM ﹠amp; 1% cysteine+ethanol 25% 3.2 ± 0.4

5%MSM ﹠amp; 5% half Guang ammonia alcohol+ethanol 0% 0

10%MSM & 0% 0

10% cysteine+ethanol

20%MSM & 0% 0

20% cysteine+ethanol

MSM: methyl sulfonyl methane

Alcohol can destroy the gastric mucosa barrier layer and cause hydrion diffuse in reverse direction and coagulation necrosis.Proved that the acute gastric mucosal lesion that alcohol brings out mediates by the deutero-free radical of oxygen.The dosage relevant with exempting from this damage is provided respectively by cysteine and methyl sulfonyl methane.In addition, these reagent are introduced body together in that avoiding can show synergistic aspect the tissue injury.It is relevant with these effects that gastric acid secretion is not had influence.

Therefore, can think that cysteine and methyl sulfonyl methane all have the cytoprotection of anti-tissue injury, and be reflected at each other and produce cooperative effect in this respect.The mechanism of believing this effect is to remove to cause the free radical of tissue injury, and this free radical is deutero-by oxygen.

B. detect methyl sulfonyl methane and/or cysteine or methyl chloride methionine sulfur then to influencing the ability that alcohol brings out the acute gastric mucosal lesion healing rate.20 Sprague-Dawley Mus of getting two kinds of sexes arbitrarily are one group, and Mus heavily is 190-270g, fasting 24 hours after gavage under the situation of etherization, 1ml40% ethanol or redistilled water are sent in the stomach with the 6FG charge pipe.After 1 hour, 24 hours and 48 hours, make animal send into the redistilled water of 1ml or the solution that cysteine, methyl chloride methionine sulfur (MMSC) and/or methyl sulfonyl methane (MSM) prepare through gavage in redistilled water equally.10 animals in every group are killed with the ether of overdose in after instiling for the second time and for the third time 6 hours, collect their gastric acid secretion thing, and analyze H as mentioned above ⁺Output, detect their stomach again, the integrity of check mucosa, and determined whether damage, carry out following observation:

Therapy shows the incidence rate % of damage animal

N=20 is for the second time behind the dosage for the third time behind the dosage

Distilled water+distilled water 0% 0%

Ethanol+distilled water 100% 80%

Ethanol and 0.5%MSM 80% 60%

Ethanol+1%MSM 60% 50%

Ethanol+5%MSM 50% 50%

Ethanol+10%MSM 50% 50%

Ethanol+20%MSM 50% 50%

Ethanol+0.5% cysteine 90% 80%

Ethanol+1% cysteine 80% 70%

Ethanol+5% cysteine 60% 60%

Ethanol+10% cysteine 60% 60%

Ethanol+20% cysteine 60% 60%

Ethanol+0.5%MMSC 90% 80%

Ethanol+1%MMSC 80% 70%

Ethanol+5%MMSC 70% 60%

Ethanol+10%MMSC 60% 60%

Ethanol+20%MMSC 60% 60%

Ethanol+0.5%MSM+0.5% cysteine 60% 30%

Ethanol+1%MSM+1% cysteine 30% 10%

Ethanol+5%MSM+5% cysteine 0% 0%

Therapy shows the incidence rate % of damage animal

N=20 is for the second time behind the dosage for the third time behind the dosage

Ethanol+10%MSM+10% cysteine 0% 0%

Ethanol+20%MSM+20% cysteine 0% 0%

Ethanol+0.5%MSM+0.5%MMSC 50% 30%

Ethanol+1%MSM+1%MMSC 20% 10%

Ethanol+5%MSM+5%MMSC 0% 0%

Ethanol+10%MSM+10%MMSC 0% 0%

Ethanol+20%MSM+20%MMSC 0% 0%

MSM: methyl sulfonyl methane

MMSC: methyl chloride methionine sulfur

Methyl sulfonyl methane and/or cysteine or methyl chloride methionine sulfur are introduced body does not obviously influence gastric acid secretion, and therefore, the effect of these reagent has nothing to do with mediating through the acid secretion.The result shows that cysteine, methyl chloride methionine sulfur and methyl sulfonyl methane can stimulate the healing of acute mucosal lesion respectively, and also showing each other can the reaction of cooperating type ground and reach the object of the invention.Because to the not influence of mentioning of sour secretor state, so can think that the mechanism by cell concentration control reaches the enhancing of healing, biological example sulfur synthetic and except removing the deutero-free radical of oxygen gives, and described free radical heals so damage because tissue is had direct deleterious effects.

According to these two groups experiments; can learn the aminoacid and the methyl sulfonyl methane energy protective tissue of sulfur-bearing; comprise skin, anti-wound (cytoprotective) and can strengthen as yet the damage recovery from illness of not curing, also think these favourable effects by its together administration can strengthen synergistically.And these the two kinds of reagent concentration separately that obviously is used for embodiment 1 preparation is normally preferred.

Embodiment 4: clinical trial

Carry out pre-determined random double blinding controlled experiments in patient, patient enters matched group (polyethyleneglycol cetyl ether (cetomacrogol) A) or enters the active treatment group by the extraction seal envelopes all is at random.The treatment coding is only just torn when experimental period finishes.The preparation of all uses is all pressed embodiment 1 and is described preparation in detail.

After getting rid of the patient that can not fully detect, carry out following observation:

A. the ability of checking the sun-proof effect of embodiment preparation that 1.A describes and protection patient thereof to prevent to be exposed to the sun skin burn, erythema after following a few hours, itch and come off.12 example contrast case (10 women and 2 male are arranged; the range of age is 18 years old-31 years old; average 25 years old) and 14 example treatment case (8 women and 6 male; the range of age was from 18 years old to 39 years old; average 28 years old); be coated with 7 days (directly exposing the time limit under the sunlight) of cream treatment every day before exposure, and its amount is the zone of the full desire protection of lid enough.Whole illeffectss that active treatment can provide fully protection (100%) to avoid exposing under the sunlight to be produced.This protection can expand to and prevent skin burn or stimulation.Matched group does not have protective effect.

B. check the curative effect of the described preparation of embodiment 1.C in the contact dermatitis in treatment.Treat twice every day, continue 5 days.There are 10 contrast cases (5 male and 5 women, the range of age is from 18-to 34-year-old, average 22 years old) and 12 to treat case (8 male and 4 women, the range of age is 20-39 year, average 26 years old).All fully recover although when this off-test, notice all active treatment case (100%) dermatitis, have only 1 contrast case (10%) can prove this sound response.

C. hyperkeratosis is a kind of hypertrophy dermatosis, represents epidermal hyperplasia, and the possibility of deterioration is arranged.Conditioning influences expose portion, especially face and the arm top of middle age skin.The treatment of these damages is by the described preparation of twice coating embodiment 1.D every day, continues 4 weeks (21 cases, 12 women and 11 male, the range of age is 55-69 year, average 63 years old), cause injury region to come off fully, all cases are normal skin and replace.Noticed that any contrast case (the range of age is 54-67 year, average 61 years old for 20 patients, 13 women and 7 male) is all reactionless.Therefore, can think the reparation that used preparation can the chafe damage.

D. check the described preparation of embodiment 1.B to treat 10 days curative effect of this disease owing to the symptom that exposes caused skin burn generation under the sunlight with by it being coated in the skin injury position every 8 hours in control.11 treatment cases (6 male and 5 women, the range of age is 21 years old-33 years old, average 26 years old) and 13 contrast cases (8 women and 5 male, the range of age is 19 years old-35 years old, average 25 years old) are arranged.In treatment 24 hours, the symptom of burning in all members of active treatment group (hyperesthesia, itch, bitterly) is under control fully, and matched group does not then have.End active treatment the 5th day to the 7th day, the skin of all calcinations all comes off, and has all recovered normal skin in the 10th day all case of treatment.Have only 2 example contrast cases (15%) sx in 24 hours, 4 example contrast cases (31%) were only taken off its skin ambustion and were occurred normal skin on the 10th day in treatment after 5-7 days.

E. the described preparation of embodiment 1.D is to keeping the smooth of skin and avoid its check coarse and/or crackle is renderd a service, and this carries out in one group of women, uses the beauty treatment cream of some form before this group women tests already, and their former no any skin medical history.All participate in the case of this test and all abandon using their original cream, enter matched group or the active treatment group is at random, instruct them that cream is used for hands and/or face, once and it is spent the night, continue 2 months before sleep every day.20 cases (the range of age is 18-26 year, average 23 years old) are arranged in the active treatment group, 21 cases (the range of age is 18-25 year, average 21 years old) are arranged at matched group.When this off-test, 3 reference examples (14%) and 18 active treatment cases (90%) show that cream that they use is better than the cream of their the original conduct beauty treatment usefulness of using, and avoids it coarse because this cream can keep skin smooth.Therefore, can determine capable skin vitality and its resistivity of raising of keeping of used preparation to environmental stimulus thing and infringement.

F. the women who has an obvious dermatosis signal of skin aging mainly is emerging in facial and hand (shortage robustness, coarse, plump, keratosis, crackle and wrinkle), such women is chosen at random the use described preparation for treating of embodiment 1.A or compares group, treat every day twice, continue 6 months, and then the coating 6 months of spending the night merely.43 routine active treatment (the range of age is 53-67 year, average 56 years old) and 41 example contrast cases (the range of age is 52-65 year, average 57 years old) are arranged, and these cases can be done complete detection.After 3 months, the case of all active treatment groups is all observed has the more smooth skin that does not have crackle, has taken off whole keratinization damages.By 6 months, these advantages caused skin firm, and obviously wrinkle seldom.And matched group does not have an example can obtain any benefit with regard to improving the degeneration order of severity.

Treat after 1 year, all active treatment cases all obtain smooth, firm, flawless skin, do not have any keratosis, and wrinkle is very not obvious, have at least 36 examples (84%) almost to cannot see.And these incomes all there are not acquisition in any member of matched group.

Therefore, can think that used preparation is being effective especially aspect the order of severity of degeneration skin variation of being noted by the aging introducing that causes and the improvement this variation of appearance already.

G. select facial women with obvious wrinkle to accept the described preparation of embodiment 1.D or compare group arbitrarily, elder generation treats twice every day, continues 6 months, and (application spends the night) continues 18 months then once a day.Wrinkle is plotted on the special-purpose drawing, and any improvement (degree is not obvious) of its outward appearance is calculated to improving percentage ratio.Work as matched group (n=45 after 6 months, the range of age is 50-59 year, average 54 years old) when obtaining 5% improvement, active treatment group (n=48, the range of age is 48-59 year, average 56 years old) in equally during this period of time, reach 71% improvement, when this off-test (2 years), matched group improves percentage ratio and has expanded 10% to, yet the same improvement of active treatment group has reached 89%.The remarkable improvement of wrinkled appearance is relevant with the improvement of skin of face slickness and robustness.After wrinkle becomes not too obviously, the latter's the chances are principal element.And during this off-test, do not observe new wrinkle development.

These advantages reflect that used preparation is changing order of severity struggle with degeneration of skin and weakening aspect its rising profitable.

H. it is involutory comprehensively and epidermis undertissue is close to press on the skin center line laparotomy otch, at random 50 such patients are divided to active treatment group (22 male and 28 women, the range of age is 18-53 year, average 31 years old), the described preparation of embodiment 1.D is spread on wound last 10 day once a day with conventional dressing, other 52 patients (23 male and 29 women, the range of age is 18-57 year, average 34 years old) are divided into matched group at random and do similar treatment.Continued again to test in 6 months not observe 1 routine active treatment case generation wound dehiscence, incisional hernia, wound pigmentation or hypertrophy spot at whole 1 year.In matched group, wound dehiscence takes place in 1 patient, and incisional hernia takes place two patients (4%), and the wound hyperpigmentation takes place 3 patients (6%), and the spot tumor takes place other 3 patients (6%).

Therefore, can conclude that used preparation can not only stimulating wound healing, and can also keep the integrity of reparation.

1. make 12 quadriplegia patients (8 male and 4 women, the range of age is 23-59 year, average 31 years old) arbitrarily select for use twice of the coating of embodiment 1.C institute series preparation, every day, physical therapy simultaneously 6 months, and with other 10 patients (6 male and 4 women, the range of age is 19-53 year, average 29 years old) arbitrarily elect matched group as and similarly treat.Pressure ulcer (decubital ulcer) does not all take place in any member of active treatment group, in 3 members (30%) of matched group pressure ulcer has taken place then.

Therefore, available another evidence is that used preparation can improve the resistance of skin to mechanical trauma.

J. reached among the patient of 9-18% by the third degree burn area, burn area is treated, every day twice, continued for 3 weeks.Choose at random 25 patients (15 male and 10 women, the range of age is 18-41 year, average 29 years old) accept the described preparation of embodiment 1.B, compare group (18 male and 8 women and choose at random other 26 patients, the range of age is 18-44 year, average 30 years old).Active treatment contrasts cream alleviating the pain that caused by burn, not accommodating on the degree of itching obviously more effectively, and causes having the good healing of cosmetic result, simultaneously pigmentation or variable color much less.Therefore, used preparation can strengthen the agglutination of skin.

K. classify down that deep burn spreads all over lower limb and area reaches the excision of 9-12% and the transplantation of segment thickness skin as, before the wound dressing on the zone of transplanting the described preparation of embodiment 1A of coating capacity or contrast cream earlier.12 patients are divided at random to active treatment group (8 women and 4 male, the range of age is 18-38 year, average 25 years old) with 14 patients divide at random to matched group (7 women and 7 men age scopes are 18-43 year, average 29 years old).When dressing is removed in after transplanting 5 days, in all members of active treatment group, all can be observed complete successful processing.Yet two contrast cases (14%) show the migration process failure.This test reflects that used active treatment can improve dermatoplastic ability.

L. choose at random incompetent perforating veins and cause that patient's (appear itch, exudate, erythema and squama) of the lower inside dermatitis of lower limb 1/3rd accepts the described preparation of embodiment 1.C or compares group and treated for 4 weeks, when spending the night and being seated or during rest, foot is raised, be coated with cream every day once, use the classification compression bandage below knee at the open weave terylene with above the cotton yarn dressing.Compression bandage is depressed the ankle of about 40mmHg and is dropped to about 16mmHg at one's knees and comprise one deck crape ace bandage, then be one deck Elset binder, is the cohesion binder of one deck Coban then.Choose at random 32 patients (20 women and 12 male, the range of age is 30-71 year, average 55 years old) to the active treatment group with choose at random 30 patients (19 women and 11 male, the range of age is 32-69 year, average 53 years old) to matched group.When this off-test, all active treatment case (100%) dermatitis is healing fully all, and the skin condition of getting well.Yet matched group only has 21 patients (70%) to reach this gratifying effect.

M. there is swelling ulcer the inboard that chooses at random the lower limb bottom, the not enough 10cm of surface area ², do not treat in the past and do not infect or the patient of the loose lower limb edema of association yet, with the described preparation for treating of embodiment 1.D or compare group.Choose at random 40 patients (25 women and 15 male, the range of age is 28-71 year, average 57 years old) and make the active treatment group, compare group and choose at random 42 patients (23 women and 19 male, the range of age is 30-74 year, average 54 years old).Remove around the skin of ulcer any no vitality all around with warm olive oil, wash ulcer with normal saline then, remove any lax tissue again.After coating cream, ulcer place open weave terylene and cotton cloth dressing.Skin around ulcer is handled with propylene glycol monostearate, then below knee by the above-mentioned classification compression bandage that adds in dressing.Repeat this program every day, continue 7 days, repeat up to the ulcer recovery from illness then weekly or this off-test during up to 3 months.Advise that patient will raise footpost in bed, shank is pumped, no matter when will take a walk as far as possible, when being seated, will raise lower limb to avoid long-term immobilization.

Active therapy heals ulcer in 37 routine patients (93%) and 28 example contrast cases (67%) fully, thereby proves the capable swelling ulcer healing that stimulates of used preparation.

Embodiment 5: toxicity test

Preparation methyl sulfonyl methane (MSM) and DL-cysteine hydrochlorate (CYS) or the solution of methyl chloride methionine sulfur (MMSC) in redistilled water are to provide following ingredients:

1.1%MSM+1%CYS

2.5%MSM+5%CYS

3.10%MSM+10%CYS

4.15%MSM+15%CYS

5.1%MSM+1%MMSC

6.5%MSM+5%MMSC

7.10%MSM+10%MMSC

8.15%MSM+15%MMSC

With two kinds of sexes, 10 Sprague-Dawley Mus of heavy 200-300 gram are one group many groups of fasting 24 hours, then, under a small amount of etherization left the ilium ditch by above-mentioned a kind of preparation of peritoneal injection, subcutaneous injection or gastrostome instillation 1ml, observe animal and allow feed and beverage after 24 hours, observed again 6 days.The dosage ether that overuses kills animal, and dissects all corpse.

In Syrian gold hamster (heavy 150-200 gram) and nude mice (nudemice) (40-50 grammes per square metre), repeat same test.Before latter's administration and after, the fasting phase reduces to 12 hours, and only gives every kind of preparation 0.25ml.

Death and uncomfortable in each group, occurs, or in any case, all do not run into significantly tired brain, excitement, drowsiness, withdrawal, depression, vomiting or diarrhoea.Obduction does not show not to be had to cause variation because of medication.

Therefore, can think in very wide dosage range that used preparation can not show any deleterious effects or attractive acute toxicity, thereby can in the therapeutic domain of selecting, use safely.

In the group of 20-48 between year, in the morning, on face, neck, shoulder, be coated with embodiment 1 described each preparation 5g one time at 10 healthy male volunteers, the range of age, be coated with morning once, and then be coated with at night once or be coated with once in per 8 hours.Treatment continues 10 days, and application is applied on the skin of face, neck and shoulder, massages a few minutes lightly, and it was kept 3 hours.

In 10 days process of the test, carry out a medical examination once every day.Similarly, carry out urine examination standard blood and biochemical test (comprising liver and kidney function test, blood glucose, serum amylase and flood gas) every day, finish the electrocardiogram of cardiac's enzyme level estimated value every other day.

Finish all treatment plans giocoso, without any significantly allergia or adverse reaction.In addition, used therapy can toxigenicity.Therefore, can think that it is safe that embodiment 1 described preparation is used for the people in the dosage range of recommending.

Although methyl sulfonyl methane and sulfur-containing amino acid be preferably equivalent (by weight) use usually, in cooperative compositions of the present invention, other ratio also can be used.In general, used ratio is 10: 1-1: 10(is by weight), be preferably 5: 1-1: 5, preferably about 1: 1(is by weight).Though can think, a seed amino acid may be different with another kind of aminoacid preferred proportion, yet the preferred proportion of methyl sulfonyl methane and cysteine or methionine is approximately 5: 2 or 5: 1 as mentioned above.

Claims (13)

1, a kind of cooperative compositions, said composition contains the aminoacid of methyl sulfonyl methane and a kind of sulfur-bearing.

2, by a kind of compositions of claim 1, wherein said aminoacid is selected from cysteine, cysteamine, cystine, methionine, wherein the methionine carboxyl is esterified and S-is methyl substituted, ternary sulfonium derivant.

3, by a kind of compositions of claim 2, wherein said carboxyl has been had the low alkyl group esterification of 1-6 carbon atom.

4, by a kind of compositions of claim 2, wherein said methionine derivant comprises bromination, iodate or chlorination methionine-S-methyl sulfur.

5, by each a kind of compositions of claim 1-4, wherein said methyl sulfonyl methane and amino acid content ratio are by weight from 1: 5 to 5: 1.

6, a kind of methyl sulfonyl methane and sulfur-containing amino acid of containing can be used for preparing for skin condition, dermatosis and the trauma care compositions with preparation.

7, a kind of containing by each compositions of claim 1-5 and the mixed uniformly preparation of pharmaceutical carrier, it can be used in the treatment of skin condition, dermatosis and wound.

8, a kind of topical preparation by claim 7, said preparation at least respectively contains 0.5%W/W methyl sulfonyl methane and aminoacid.

9, by a kind of preparation of claim 8, said preparation respectively contains methyl sulfonyl methane and the aminoacid of 1-20%W/W.

10, by a kind of oral formulations of claim 7, said preparation is the unit dose type, and per unit dosage respectively contains methyl sulfonyl methane and the aminoacid of 100-500mg.

11, the method for the treatment of a kind of skin condition, dermatosis or wound or prevention, this method comprise introduces body with effective dose by claim 7 preparation.

12, by a kind of method of claim 11, wherein will be applied to skin by the topical preparation of claim 8.

13, by a kind of method of claim 12, twice of every day at least when wherein described topical preparation being applied to skin.