CN101128193B - Anti-radical agents - Google Patents

Abstract

The invention discloses compounds of the formulae (1), (2) and selected hindered nitroxyl, hydroxylamine and hydroxylamine salt compounds such as the compound of formula (3), wherein Gi is hydrogen; C1-C22alkyl; C1-C22alkylthio; C2-C22alkylthioalkyl; C5-C7cycloalkyl; phenyl; C7-C9phenylalkyl; or SO3M; G2 is C1-C22alkyl; C5-C7cycloalkyl; phenyl; or C7-C9phenylalkyl; E is oxyl or hydroxyl; V is -O-; or -NH-; a is 0 or 1 or 2; b, c and d and g are each independently of one another 0 or 1; e is an integer from 1 to 4; f, m, n and p are each independently of one another an integer from 1 to 3; q is 0 or an integer from 1to 3; Q, T and G3 are as defined in claim 1; G4 and G5 are each independently of the other hydrogen; or C1-C22alkyl; exhibit marked antiinflammatory action.

Description

Antifree radical agent

The present invention relates to the phenol of carbon especially or ester/amide bridging or its lactone or some sterically hindered amine purposes as forms of pharmacologically active agents, and the pharmaceutical composition that contains them skin composition (dermatological compositions) especially.The invention still further relates to these chemical compounds and be used to prepare damage (radical induced impairment) that the treatment free radical brings out purposes (as antidotal purposes) as the medicine or the preparation of inflammatory or allergic conditions, collagen protein damage, DNA damage or reperfusion injury.

Using glucocorticoid topical therapeutic inflammatory and allergic conditions is standard practice.Well-known these chemical compounds may have undesirable side effects.

Because they are transdermal fully, contains the anti-inflammatory drug local application effectively such as ketoprofen, BW755c, piroxicam, diclofenac or indomethacin (indomethazin) therapeutic agent, and can only systemic administration.Also the someone proposes the performance (reaching the document of wherein quoting referring to EP-A-1366763) that some 2, 2-Oxydiphenol have antioxidation, antiinflammatory and antiallergic (antiallergic).

The purpose of this invention is to provide have unexpected pharmacology's performance, particularly antioxidation, antiinflammatory and the antiallergic performance pharmaceutical composition of (especially when use the part).

Have been found that the chemical compound (1) of following formula and/or (2) and/or (3) show tangible removing free radical and antiinflammatory action on one's body in the in vitro tests of cell that people volunteer carries out and enzyme and in vivo test, demonstrate advantages of good skin and cell compatibility simultaneously,

And/or

And/or

(3) the sterically hindered nitroxyl chemical compound of following formula, steric hindrance hydroxylamine compound, steric hindrance hydroxylamine salt chemical compound

Wherein in following formula

G ₁Be hydrogen; C ₁-C ₂₂Alkyl; C ₁-C ₂₂Alkylthio group; C ₂-C ₂₂Alkylthio alkyl; C ₅-C ₇Cycloalkyl; Phenyl; C ₇-C ₉Phenylalkyl; Or SO ₃M;

G ₂Be C ₁-C ₂₂Alkyl; C ₅-C ₇Cycloalkyl; Phenyl; Or C ₇-C ₉Phenylalkyl;

Q is-C _mH _2m-;

-C _mH _2m-NH; The group of following formula

Or (1b)

T is-C _nH _2n-;-(CH ₂) _n-O-CH ₂-; Phenylene;

Or the group of formula (1c)

V is-O-; Or-NH-;

A is 0; 1; Or 2;

B, c and d and g are 0 or 1 separately independently of one another;

E is the integer of 1-4;

F is the integer of 1-3; And

M, n and p are the integer of 1-3 separately independently of one another;

Q is 0 or the integer of 1-3;

If e=1, then G ₃Be hydrogen; C ₁-C ₂₂Alkyl; C ₅-C ₇Cycloalkyl; C ₁-C ₂₂Alkylthio group; C ₂-C ₂₂Alkylthio alkyl; C ₂-C ₁₈Thiazolinyl; Phenyl C ₁-C ₁₈Alkyl or C ₁-C ₁₈Alkyl phenyl; M; SO ₃M;

The group of following formula (1d)

Or (1f)

Or G ₃For by OH and/or by C ₂-C ₂₂The propyl group that alkanoyloxy replaces;

M is an alkali metal; Ammonium; H;

If e=2, then G ₃Be direct key (direct bond);-CH ₂-; Or-S-; Or G ₃For by OH or C ₂-C ₂₂The propyl group that alkanoyloxy replaces;

If e=3, then G ₃Group (1g) for following formula

Or

If e=4, then G ₃For

G ₄And G ₅Be hydrogen separately independently of one another; Or C ₁-C ₂₂Alkyl;

A ₁And A ₂Be the alkyl of 1-4 carbon atom or independently together for pentamethylene (pentamethylene),

Z ₁And Z ₂Methyl or Z respectively do for oneself ₁And Z ₂Form linking group together, this linking group can be replaced by ester group, ether, hydroxyl, oxo, cyanohydrin base (cyanohydrin), acylamino-, amino, carboxyl or carbamate groups in addition,

H is a positive changes and j is the negative charge number,

X is inorganic or organic anion, and

Wherein the total electrical charge of cations h equals the total electrical charge of anion j.

This chemical compound can use separately or use with each other mixture and/or with other mixture of ingredients form, for example those that hereinafter further describe.Therefore the present invention relates to a kind of pharmaceutical composition, it comprises at least a chemical compound in formula (1) and/or (2) and/or (3), and pharmaceutically suitable carrier or adjuvant, and the chemical compound of formula (1), (2) and/or (3) is used to prepare skin injury and the medicine of inflammatory and allergic conditions or the purposes of preparation such as cosmetics or pharmaceutical preparation that treatment or prevention free radical bring out.

The chemical compound of formula 1, wherein e is 1, comprises spacer groups Q and (CO)-V usually, eligible b=c=1.Also can use the chemical compound of following formula

Known free radical oxygen class (ROS) is understood lipid oxide, catabolic enzyme and stromatin, is influenced this DNA or RNA, and causes skin precocious old and feeble by the destruction of component in desiccation, elasticity disappearance, strong stimulation and the promotion skin.The generation of inflammation and ROS can activate matrix metalloproteinase (MMP) and cause the oxidative damage of pair cell albumen, lipid and carbohydrate.

MMP is one group of energy degradation of cell epimatrix (ECM) composition (as collagen protein, elastin laminin, fibronectin, gelatin, laminin), causes that the zinc dependency endopeptidase of (dispigmentation) reaction of fading crease lines appears and in the skin of photo-aging.Chemical compound of the present invention can strengthen endogenous anti-oxidative defense system, comprises enzyme component such as glutathion peroxidase, catalase, erythrocuprein, metallothionein (Methallothionein); Or non-enzyme component such as glutathion, vitamin E, vitamin C, pantothenylol, beta-carotene.

After being applied to skin; this compounds can be protected lipid, lipoprotein, cell membrane, the low molecular compound in intercellular and the born of the same parents, as lipid, sugar, unsettled aminoacid (for example containing mercapto), glutathion, also have macromole such as albumen, proteoglycan and glycosaminoglycan (glycosaminoglycane) to exempt from direct oxidation.

Other effect of those materials be its commute by the protective effect of the composition of the described preparation of air oxygen oxidation, this can provide high product stability and the benefit of long shelf life.The carrier emulsion of part medicine or beauty treatment is lipid and the emulsifying agent that contains lipid fragments, makes them that the inductive chemical conversion with the oxygen reaction take place easily.

According to chemical constitution and the dissolubility in typical medicine or cosmetics carrier heterogeneous, this compounds can be hydrophilic or lipophilic.The selection of best antioxidant not only depends on the dissolubility in some carrier system, and after its interaction of also being subjected to not expect, local application preparation with carrier penetration performance, the issuable and radical reaction of skin cytotoxicity or inhibitive ability of immunity product, have or do not have that ultraviolet light is coefficient to be influenced.

The radical damage of having described in more detail in animal and human's organism is arranged in US-4698360, this may prevent by chemical compound of the present invention-.

Chemical compound of the present invention, the chemical compound of formula (1), (2) and/or (3) for example, be used for the treatment of inflammatory and allergic conditions and (for example be described in Skaper etc., Free Radical Biology and Medicine22, and be used for the treatment of the disease that relates to the cell proliferation obstacle 669-78 (1997)).They are preferred for the topical therapeutic of untoward reaction that free radical brings out such as inflammatory and allergic conditions, collagen protein damage, reperfusion injury, DNA-damage, are particularly useful for skin treating.

Vitro detection shows that chemical compound of the present invention suppresses the formation of different medium, and these different media are factors important in the inflammation.

Chemical compound of the present invention works as free radical inhibitors.They represent lipoxygenase/-cyclooxygenase-2 inhibitors, promptly they can interfere inflammatory cascade (inflammatory cascade).Can show the anti-inflammatory agent of the erythema that they bring out as UV and work.They show antiinflammatory and antioxidation, and it is comparable to these effects of vitamin E in some applications.

Sterically hindered nitroxyl, azanol and hydroxylamine salt chemical compound (3) are for example formula A-EE and A ^*-EE ^*

Wherein

E is oxygen base (oxy) or hydroxyl,

R is hydrogen or methyl,

At formula A and A ^*In,

N is 1 or 2,

When n is 1,

R ₁Be hydrogen, the alkyl of 1-18 carbon atom, the thiazolinyl of 2-18 carbon atom, propargyl, glycidyl is by the alkyl of 1-20 oxygen atom 2-50 carbon atom at interval, described alkyl is replaced by 1-10 hydroxyl or had not only been replaced at interval but also by described hydroxyl by described oxygen atom, or

R ₁For by carboxyl or-alkyl of 1-4 the carbon atom that COOZ replaces, wherein Z is the alkyl or phenyl of hydrogen, a 1-4 carbon atom, or wherein Z is quilt-(COO ^-) _nM ^N+The described alkyl that replaces, wherein n is that 1-3 and M are the metal ion of first, second or the 3rd main group in the periodic table of elements, or is Zn, Cu, Ni or Co, or M is group N ^N+(R ₂) ₄, R wherein ₂Be the alkyl or the benzyl of 1-8 carbon atom,

When n is 2,

R ₁Alkylidene for 1-12 carbon atom, the alkenylene of 4-12 carbon atom, the alkylidene of an xylylene or 1-50 carbon atom, the alkylidene of a described 1-50 carbon atom are replaced by 1-10 hydroxyl or had not only replaced by described oxygen atom interval but also by described hydroxyl by 1-20 oxygen atom at interval

At formula B and B ^*In,

M is 1-4,

When m is 1,

R ₂Be the alkyl of 1-18 carbon atom, the alkyl of quilt-COO-3-18 carbon atom at interval, or R ₂For-CH ₂(OCH ₂CH ₂) _nOCH ₃, wherein n is 1-12, or

R ₂Be the cycloalkyl of 5-12 carbon atom, the aryl of 6-12 carbon atom, or described aryl replaced by the alkyl of one to four 1-4 carbon atom, or

R ₂For-NHR ₃, R wherein ₃Be the alkyl of 1-18 carbon atom, the cycloalkyl of a 5-12 carbon atom, the aryl of a 6-12 carbon atom, or described aryl replaced by the alkyl of one to four 1-4 carbon atom, or

R ₂For-N (R ₃) ₂, R wherein ₃As above definition,

When m is 2,

R ₂Be the alkylidene of the alkenylene of the alkylidene of 1-12 carbon atom, a 4-12 carbon atom, xylylene, quilt-COO-2-12 carbon atom at interval, or R ₂For-CH ₂(OCH ₂CH ₂) _nOCH ₂-, wherein n is 1-12, or

R ₂Be the cycloalkylidene of 5-12 carbon atom, the inferior aralkyl of a 7-15 carbon atom or the arlydene of 6-12 carbon atom, or

R ₂For-NHR ₄NH-, wherein R ₄Be the alkylidene of 2-18 carbon atom, the cycloalkylidene of a 5-12 carbon atom, the inferior aralkyl of a 8-15 carbon atom or the arlydene of 6-12 carbon atom, or

R ₂For-N (R ₃) R ₄N (R ₃The R of)-wherein ₃And R ₄As above definition, or

R ₂For-CO-or-NH-CO-NH-,

When m is 3,

R ₂Be alkane three bases (alkanetriyl) or benzene three bases (benzenetriyl) of 3-8 carbon atom, or when m is 4,

R ₂Be alkane four bases (alkanetetrayl) or benzene four bases (benzenetetrayl) of 5-8 carbon atom, or

At formula C and C ^*In,

R ₁₀Be the alkyl of hydrogen, a 1-18 carbon atom, the cycloalkyl of a 5-12 carbon atom, the aralkyl of a 7-15 carbon atom, the alkanoyl of a 2-18 carbon atom, the enoyl-of 3-5 carbon atom or benzoyl,

X is 1 or 2,

When x is 1,

R ₁₁Be hydrogen, the alkyl of 1-18 carbon atom, the thiazolinyl of 2-18 carbon atom, propargyl, glycidyl is by the alkyl of 1-20 oxygen atom 2-50 carbon atom at interval, described alkyl is replaced by 1-10 hydroxyl or had not only been replaced at interval but also by described hydroxyl by described oxygen atom, or

R ₁₁For by carboxyl or-alkyl of 1-4 the carbon atom that COOZ replaces, wherein Z is the alkyl or phenyl of hydrogen, a 1-4 carbon atom, or wherein Z is quilt-(COO ^-) _nM ^N+The described alkyl that replaces, wherein n is that 1-3 and M are the metal ion of first, second or the 3rd main group in the periodic table of elements, or is Zn, Cu, Ni or Co, or M is group N ^N+(R ₂) ₄, R wherein ₂For the alkyl of hydrogen, a 1-8 carbon atom or benzyl or

When x is 2,

R ₁₁Be the alkylidene of 1-12 carbon atom, the alkenylene of 4-12 carbon atom, the alkylidene of an xylylene or 1-50 carbon atom, it is replaced by 1-10 hydroxyl or had not only replaced by described oxygen atom interval but also by described hydroxyl by 1-20 oxygen atom at interval,

At formula D and D ^*In,

R ₁₀As above definition,

Y is 1-4, and

R ₁₂As above-mentioned R ₂Definition

At formula E and E ^*In,

K is 1 or 2,

When k is 1,

R ₂₀And R ₂₁Be the alkyl of 1-12 carbon atom, the thiazolinyl of a 2-12 carbon atom or the aralkyl of 7-15 carbon atom independently, or R ₂₀Also can be hydrogen, or

R ₂₀And R ₂₁Replaced by hydroxyl for the alkylidene of 2-8 carbon atom or described alkylidene together, or be the acyloxy-alkylidene of 4-22 carbon atom, or

When k is 2,

R ₂₀And R ₂₁Be (CH together ₂) ₂C (CH ₂-) ₂,

At formula F and F ^*In,

R ₃₀Be the alkoxyalkyl of alkyl, benzyl, glycidyl or the 2-6 carbon atom of hydrogen, a 1-18 carbon atom,

G is 1 or 2,

When g is 1, R ₃₁As above-mentioned R ₁Definition when n is 1,

When g is 2, R ₃₁As above-mentioned R ₁Definition when n is 2,

At formula G and G ^*In,

Q ₁For-NR ₄₁-or-O-,

E ₁Be the alkylidene of 1-3 carbon atom, or E ₁For-CH ₂-CH (R ₄₂)-O-, wherein R ₄₂Be hydrogen, methyl or phenyl, or E ₁For-(CH ₂) ₃-NH-or E ₁Be direct key,

R ₄₀Be the alkyl of hydrogen or 1-18 carbon atom,

R ₄₁Be the alkyl of hydrogen, a 1-18 carbon atom, the cycloalkyl of a 5-12 carbon atom, the aralkyl of a 7-15 carbon atom, the aryl of a 6-10 carbon atom, or R ₄₁For-CH ₂-CH (R ₄₂)-OH, wherein R ₄₂As above definition,

At formula H and H ^*In,

P is 1 or 2,

T ₄According to R ₁₁Definition when x is 1 or 2,

M and Y are methylene or carbonyl independently, and for example M is that methylene and Y are carbonyl,

At formula I and I ^*In,

The repetitive structure unit that this formula is represented polymer is T wherein ₁Be ethylidene or propylene, or be repetitive structure unit from alpha olefin copolymer and alkyl acrylate or alkyl methacrylate, and wherein

Q is 2-100,

Q ₁For-N (R ₄₁)-or-O-. R wherein ₄₁As above definition,

At formula J and J ^*In,

R is 1 or 2,

T ₇According to R ₁Definition in formula A when n is 1 or 2,

T for example ₇For the octamethylene when r is 2 (1,8-octamethylene),

At formula L and L ^*In,

U is 1 or 2,

T ₁₃According to R ₁Definition, wherein n is 1 or 2 in formula A, condition is T when u is 1 ₁₃Not hydrogen,

At formula M and M ^*In,

E ₁And E ₂Difference, respectively do for oneself-CO-or-N (E ₅)-, be E wherein ₅Alkyl or the alkoxycarbonyl alkyl of 4-22 carbon atom, for example E for hydrogen, a 1-12 carbon atom ₁For-CO-and E ₂For-N (E ₅)-,

E ₃Be alkyl, phenyl, the naphthyl of hydrogen, a 1-30 carbon atom, described phenyl or described naphthyl replace by chlorine or by the benzene alkyl of the alkyl of 1-4 carbon atom or 7-12 carbon atom, or described benzene alkyl is by the replacement of the alkyl of 1-4 carbon atom,

E ₄Be the benzene alkyl of alkyl, phenyl, naphthyl or the 7-12 carbon atom of hydrogen, a 1-30 carbon atom, or

E3 and E4 are the polymethylene (polymethylene) of 4-17 carbon atom together, or described polymethylene is by the alkyl of one to four 1-4 carbon atom methyl substituted for example,

In formula N,

R ₁Suc as formula among the A to R ₁Define, wherein n is 1,

G ₃For the alkylidene of directly key, a 1-12 carbon atom, phenylene or-NH-G ₁-NH-, wherein G ₁Be the alkylidene of 1-12 carbon atom,

At formula O and O ^*In,

R ₁₀Suc as formula among the C to R ₁₀Define,

At formula P and P ^*In,

E6 is aliphatic series or the quaternary group of aromatics, for example neopentane four bases (neopentanetetrayl) or benzene four bases,

At formula T and T ^*In,

R ₅₁Be the alkyl of hydrogen, a 1-18 carbon atom, the cycloalkyl of a 5-10 carbon atom or the aryl of 6-10 carbon atom,

R52 is the alkyl of hydrogen or 1-18 carbon atom, or

R51 and R52 are the alkylidene (alkylene) of 4-8 carbon atom together,

F is 1 or 2,

When f is 1,

R50 suc as formula among the C to R ₁₁Define, wherein x is 1, or R ₅₀For-(CH ₂) _zCOOR ₅₄, wherein z is that 1-4 and R54 are the alkyl of hydrogen or 1-18 carbon atom, or R54 is metal ion or group-N (R of first, second or the 3rd main group in the periodic table of elements ₅₅) ₄, wherein R55 is the alkyl or the benzyl of hydrogen, a 1-12 carbon atom,

When f is 2, R50 suc as formula among the C to R ₁₁Define, wherein x is 2,

At formula U and U ^*In,

R ₅₃, R ₅₄, R ₅₅And R ₅₆Be the alkyl of 1-4 carbon atom or independently together for pentamethylene.

At formula V and V ^*In,

R ₅₇, R ₅₈, R ₅₉And R ₆₀Be the alkyl of 1-4 carbon atom or independently together for pentamethylene.

At formula W and W ^*In,

R ₆₁, R ₆₂, R ₆₃And R ₆₄Be the alkyl of 1-4 carbon atom or independently together for pentamethylene,

R ₆₅Be the alkyl of 1-5 carbon atom,

M is hydrogen or oxygen,

Wherein at formula X-CC and X ^*-CC ^*In

N is 2-3,

G ₁Be hydrogen, methyl, ethyl, butyl or benzyl,

M is 1-4,

X is 1-4,

When x is 1,

R ₁And R ₂Be the alkyl of 1-18 carbon atom independently, described alkyl by 1-5 oxygen atom at interval, described alkyl is replaced by 1-5 hydroxyl or described alkyl had not only replaced by described oxygen atom interval but also by described hydroxyl; The aryl of the aralkyl of the cycloalkyl of 5-12 carbon atom, a 7-15 carbon atom, a 6-10 carbon atom or described aryl are replaced or R by the alkyl of one to three 1-8 carbon atom ₁Also can be hydrogen,

Or R ₁And R ₂Be tetramethylene, pentamethylene, hexa-methylene or 3-oxo pentamethylene together,

When x is 2,

R ₁Be the alkyl of hydrogen, a 1-8 carbon atom, described alkyl by one or two oxygen atom at interval, described alkyl is replaced by hydroxyl, or described alkyl not only replaced at interval but also by hydroxyl by one or two oxygen atom,

R ₂Be the alkylidene of 2-18 carbon atom, described alkylidene by one to five oxygen atom at interval, described alkylidene is replaced by 1-5 hydroxyl, or described alkylidene had not only replaced by described oxygen atom interval but also by described hydroxyl; Adjacent, or phenylene or described phenylene replaced by the alkyl of one or two 1-4 carbon atom, or

R ₂For-(CH ₂) _kO[(CH ₂) _kO] _h(CH ₂) _k-, wherein k be 2 to 4 and h be 1 to 40, or

R ₁And R ₂With two N atoms that they connected is piperazine-1,4-two bases,

When x is 3,

R ₁Be hydrogen

R ₂For by the alkylidene of nitrogen-atoms 4 to 8 carbon atoms at interval,

When x is 4,

R ₁Be hydrogen,

R ₂For by the alkylidene of two nitrogen-atoms, 6 to 12 carbon atoms at interval,

R ₃Be the alkyl of hydrogen, a 1-8 carbon atom, described alkyl by one or two oxygen atom at interval, described alkyl is replaced by hydroxyl, or described alkyl not only replaced at interval but also by hydroxyl by one or two oxygen atom,

P is 2 or 3, and

Q is alkali metal salt, ammonium or N ⁺(G ₁) ₄,

At formula DD and DD ^*In,

M is 2 or 3,

When m is 2,

G is-(CH ₂CHR-O) _rCH ₂CHR-, wherein r is 0 to 3, and R is hydrogen or methyl, and

When m is 3,

G is a glyceryl,

At formula EE and EE ^*In,

G ₂For-CN ,-CONH ₂Or-COOG ₃, G wherein ₃Be the alkyl or phenyl of hydrogen, a 1-18 carbon atom,

X is inorganic or organic anion, as phosphate anion, phosphonium acid ion, carbanion, bicarbonate ion, nitrate ion, chloride ion, bromide ion, sulfurous acid hydrogen radical ion, sulfite ion, hydrogen sulfate ion, sulfate ion, borate ion, formate ion, acetate ion, the benzoate anion ion, citrate ion, oxalate denominationby, the tartrate anion ion, the acrylic acid radical ion, the polyacrylic acid radical ion, fumarate ion, the maleate ion, the itaconate ion, the glycolic radical ion, the gluconic acid radical ion, the malate ion, the mandelic acid radical ion, the tiglic acid radical ion, the ascorbic acid radical ion, the polymethyl acid ion, nitrilotriacetic acid(NTA), hydroxyethylethylene diamine tri-acetic acid, the carboxylic acid ion of ethylenediaminetetraacetic acid or diethylene-triamine pentaacetic acid, the diethylene-triamine-pentamethylene phosphonic acid radical ion, alkyl sulfonate ion or aryl sulfonic acid radical ion, and

Wherein the total electrical charge of cations h equals the total electrical charge of anion j.

For example, chemical compound (3) is formula A, A ^*, B, B ^*, C, C ^*, D, D ^*, Q, Q ^*, R, R ^*, S, S ^*, X, X ^*, Y, Y ^*, Z and Z ^*Those,

R is a hydrogen,

At formula A and A ^*In,

N is 1 or 2,

When n is 1,

R ₁Be hydrogen, the alkyl of 1-6 carbon atom, the thiazolinyl of 2-6 carbon atom, propargyl, glycidyl is by the alkyl of one to ten oxygen atom 2-20 carbon atom at interval, described alkyl is replaced by 1-5 hydroxyl or had not only been replaced at interval but also by described hydroxyl by described oxygen atom, or

R ₁For by carboxyl or-1-4 carbon atom alkyl that COOZ replaces, wherein Z is the alkyl of hydrogen or 1-4 carbon atom,

When n is 2,

R ₁Be the alkylidene of 1-8 carbon atom, the alkenylene of 4-8 carbon atom, the alkylidene of 1-20 carbon atom, it is replaced by 1-5 hydroxyl or had not only replaced by described oxygen atom interval but also by described hydroxyl by 1-10 oxygen atom at interval,

At formula B and B ^*In,

M is 1 or 2

When m is 1,

R ₂Alkyl or R for 1-4 carbon atom ₂Be CH ₂(OCH ₂CH ₂) _nOCH ₃, wherein n is 1 to 12, or

R ₂Be phenyl, or described phenyl is by one to three methyl substituted,

R ₂For-NHR ₃, R wherein ₃Be the alkyl or phenyl of 1 to 4 carbon atom, or described phenyl is by one or two methyl substituted,

When m is 2,

R ₂Be the alkylidene of 1 to 8 carbon atom, the alkenylene of 4 to 8 carbon atoms, or R ₂For-CH ₂(OCH ₂CH ₂) _nOCH ₂-, wherein n is 1-12,

R ₂Be NHR ₄NH, wherein R ₄Be the inferior aralkyl of 2-6 carbon atom, a 8-15 carbon atom or the arlydene of 6-12 carbon atom,

R ₂For-CO-or-NHCONH,

At formula C and C ^*In,

R ₁₀For hydrogen or, the alkanoyl of a 1-3 carbon atom,

X is 1 or 2,

When x is 1,

R ₁₁Be the alkyl or the glycidyl of hydrogen, a 1-6 carbon atom,

R ₁₁For by carboxyl or-1-4 carbon atom alkyl that COOZ replaces, wherein Z is the alkyl of hydrogen or 1-4 carbon atom,

When x is 2,

R ₁₁Be the alkylidene of 1-6 carbon atom,

At formula D and D ^*In,

R ₁₀Be hydrogen,

Y is 1 or 2,

R ₁₂As above-mentioned R ₂Definition,

At Y, Y ^*, Z and Z ^*In,

X is 1 or 2,

When x is 1,

R ₁And R ₂Be the alkyl of 1-4 carbon atom independently,

Or R ₁And R ₂Be tetramethylene or pentamethylene together,

R ₂Be the alkyl of hydrogen or 1-4 carbon atom, described alkyl is replaced by hydroxyl,

When x is 2,

R ₁Be the alkyl of hydrogen, a 1-4 carbon atom, described alkyl hydroxy replaces,

R ₂Be the alkylidene of 2-6 carbon atom,

R ₃As above definition.

For example, chemical compound (3) is formula A, A ^*, B, B ^*, C, C ^*, D, D ^*, Q, Q ^*, R and R ^*Those,

R is a hydrogen,

At formula A and A ^*In,

H is 1,

R ₁For the alkyl of hydrogen, a 1-4 carbon atom, glycidyl, by one or two oxygen atom 2-4 carbon atom alkyl at interval, described alkyl is replaced by one or two hydroxyl or had not only been replaced at interval but also by described hydroxyl by described oxygen atom, or

R ₁Be the 1-4 carbon atom alkyl that quilt-COOZ replaces, wherein Z is the alkyl of hydrogen or 1-4 carbon atom,

At formula B and B ^*In,

M is 1 or 2,

R ₂Alkyl or R for 1-4 carbon atom ₂Be CH ₂(OCH ₂CH ₂) _nOCH ₃, wherein n is 1-4,

When m is 2,

R ₁Be the alkylidene of 1-8 carbon atom,

At formula C and C ^*In,

R ₁₀Be the alkanoyl of hydrogen or 1 or 2 carbon atom,

X is 1 or 2,

When x is 1,

R ₁₁Be the alkyl or the glycidyl of hydrogen, a 1-4 carbon atom,

R ₁₁Be the 1-4 carbon atom alkyl that quilt-COOZ replaces, wherein Z is the alkyl of hydrogen or 1-4 carbon atom,

When x is 2,

R ₁₁Be the alkylidene of 1-6 carbon atom,

At formula D and D ^*In,

R ₁₀Be hydrogen,

Y is 1 or 2,

R ₁₂As above-mentioned R ₂Definition.

Selected sterically hindered nitroxyl, azanol and hydroxylamine salt chemical compound (3) preferably meet following formula

Wherein E is oxygen base or hydroxyl and G ₃, V, c define suc as formula (1), or its salt.

Chemical compound (3), suc as formula those of A-EE, those of following formula (3) especially, can itself form or use with the form of suitable acid-addition salts, as for example at above-mentioned formula A ^*-EE ^*Shown in.For example these chemical compounds are pharmaceutically useful inorganic or organic acid salt.Available acid-addition salts comprise form with mineral acid those as chloride or sulfate, or form with organic acid those, organic acid is sulfonic acid or carbonic acid for example, for example be hydrogen (or suitably time dihydro) phosphate, phosphonate, carbonate, bicarbonate, nitrate, chloride, bromide, bisulfites, sulphite, disulfate, sulfate, borate, formates, acetate, benzoate, citrate, oxalates, tartrate, acrylates, polyacrylate, fumarate, maleate, itaconate, oxyacetate, gluconate, pyruvate, malate, mandelate, tiglic acid salt, Ascorbate, poly-methyl acrylate, nitrilotriacetic acid(NTA), hydroxyethylethylene diamine tri-acetic acid acid, the carboxylate of ethylenediaminetetraacetic acid or diethylene-triamine pentaacetic acid acid, diethylene-triamine-pentamethylene phosphonic acid salt, alkylsulfonate or arylsulphonate are mesylate when suitable and favourable, benzoate, oxalates or acetate; These ions also meet the preferred meaning of X.Salt is preferably officinal salt.Officinal salt is mainly the salt of acid known in the art, and for example acid is as alkane carboxylic acid (C especially ₁-C ₄Acid) salt; Two or polycarboxylic acid and/or hydroxy carboxylic acid such as oxalic acid, malonic acid, succinic acid, fumaric acid, citric acid, maleic acid, tartaric acid, lactic acid, glucuronic acid and other sugared deutero-acid, these acid have two kinds of enantiomeric forms under optically active situation; Phosphoric acid, sulphuric acid, methanesulfonic acid, toluenesulfonic acid, benzoic acid; Some preferred salt comprise hydrochlorate, hydrobromate, hydriodate, benzoate, phosphate, hydrophosphate, sulfate, disulfate, especially citrate.Preferably, for example, citrate, hydrochlorate, oxalates.

C ₁-C ₂₂Alkyl is the straight or branched alkyl, as methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, sec-butyl, the tert-butyl group, amyl group, isopentyl or tertiary pentyl, heptyl, octyl group, iso-octyl, nonyl, decyl, undecyl, dodecyl, myristyl, pentadecyl, cetyl, heptadecyl, octadecyl or eicosyl.

C ₁-C ₂₂Alkylthio group is the straight or branched alkylthio group, as methyl mercapto, ethylmercapto group, positive rosickyite base, iprotiazem base, positive butylthio, secondary butylthio, uncle's butylthio, penta sulfenyl, heptan sulfenyl, hot sulfenyl, different hot sulfenyl, the ninth of the ten Heavenly Stems sulfenyl, the last of the ten Heavenly stems sulfenyl, hendecane sulfenyl, dodecane sulfenyl, tetradecane sulfenyl, pentadecane sulfenyl, hexadecane sulfenyl, heptadecane sulfenyl, octadecane sulfenyl or eicosane sulfenyl.

C ₂-C ₂₂The above-mentioned alkylthio group of alkylthio alkyl for being connected with alkyl by its sulphur atom, wherein all groups contain 2-22 carbon atom.

C ₂-C ₁₈Thiazolinyl is, for example, pi-allyl, methallyl (methallyl), isopropenyl, crotyl, 3-cyclobutenyl, isobutenyl ,-positive penta-2,4-dialkylene, 3-methyl-but-2-ene base ,-positive oct-2-ene base ,-positive 12-2-thiazolinyl, different laurylene base ,-positive 12 carbon-2-thiazolinyl or or-positive moroctic acid-thiazolinyl.

C ₅-C ₇Cycloalkyl is cyclopenta, suberyl or is preferably cyclohexyl.

C ₇-C ₉Phenylalkyl comprises phenylpropyl (as cumyl), phenethyl, is preferably benzyl.

M is generally Li as alkali metal, Na, K, Cs.

The useful chemical compound of formula of the present invention (1) and (2) comprises listed those in the table 1:

Available bulky amine chemical compound (3) comprises following: sterically hindered nitroxyl, azanol and hydroxylamine salt chemical compound, and it is selected from:

Two (1-oxygen base----2,2,6,6-tetramethyl piperidine-4-yl) sebacate;

Two (1-hydroxyl----2,2,6,6-tetramethyl piperidine-4-yl) sebacate;

1-hydroxyl----2,2,6,6-tetramethyl-4-acetoxyl group piperidines citrate;

1-oxygen base-2,2,6,6-tetramethyl-4-acetylamino piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines disulfate;

1-oxygen base-2,2,6,6-tetramethyl-4-oxo-piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-Piperidineacetic acid salt;

1-oxygen base-2,2,6,6-tetramethyl-4-methoxyl group-piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-methoxyl group-piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-methoxyl group-Piperidineacetic acid salt;

1-oxygen base-2,2,6,6-tetramethyl-4-acetoxyl group piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines;

1-oxygen base-2,2,6,6-tetramethyl-4-propoxyl group piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-propoxyl group Piperidineacetic acid salt;

1-hydroxyl-2,2,6,6-tetramethyl-4-propoxyl group piperidines;

1-oxygen base-2,2,6,6-tetramethyl-4-(2-hydroxyl-4-oxo amoxy) piperidines;

1-hydroxyl-2,2,6,6-tetramethyl-4-(2-hydroxyl-4-oxo amoxy) Piperidineacetic acid salt;

1-oxygen base-2,2,6,6-tetramethyl-4-hydroxy piperidine;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine chloride;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine acetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine disulfate;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine citrate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) citrate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) citrate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) edetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) edetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) edetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) diethylentriamine pentacetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) diethylentriamine pentacetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) diethylentriamine pentacetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) nitrilotriacetic acid(NTA) salt;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) nitrilotriacetic acid(NTA) salt;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) nitrilotriacetic acid(NTA) salt;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) diethylene-triamine-pentamethylene phosphonic acid salt;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) diethylene-triamine-pentamethylene phosphonic acid salt; With

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) diethylene-triamine-pentamethylene phosphonic acid salt.

Sterically hindered nitroxyl, azanol and the hydroxylamine salt chemical compound of preferred formula (3) are selected from:

1-oxygen base-2,2,6,6-tetramethyl-4-hydroxy piperidine;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine chloride;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine acetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine disulfate;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine citrate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) citrate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) citrate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) edetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) edetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) edetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) diethylentriamine pentacetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) diethylentriamine pentacetate; With

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidine) diethylentriamine pentacetate.

For example, formula (3) chemical compound is to be selected from following hydroxylamine salt:

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine citrate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) citrate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) citrate;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine diethylentriamine pentacetate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) diethylentriamine pentacetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) diethylentriamine pentacetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) diethylentriamine pentacetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) diethylentriamine pentacetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine edetate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) edetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) edetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) edetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines citrate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) citrate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) citrate;

1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines diethylentriamine pentacetate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) diethylentriamine pentacetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) diethylentriamine pentacetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) diethylentriamine pentacetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) diethylentriamine pentacetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines edetate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) edetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) edetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-oxo-piperidines) edetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines citrate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) citrate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) citrate;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines diethylentriamine pentacetate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) diethylentriamine pentacetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) diethylentriamine pentacetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) diethylentriamine pentacetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) diethylentriamine pentacetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines edetate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) edetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-acetylamino piperidines) edetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-hydroxy piperidine) edetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines citrate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) citrate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) citrate;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines diethylentriamine pentacetate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) diethylentriamine pentacetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) diethylentriamine pentacetate;

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) diethylentriamine pentacetate;

Five (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) diethylentriamine pentacetate;

1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines edetate;

Two (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) edetate;

Three (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) edetate; With

Four (1-hydroxyl-2,2,6,6-tetramethyl-4-acetoxyl group piperidines) edetate.

Above-mentioned counter ion is ethylenediaminetetraacetic acid (EDTA), diethylene-triamine pentaacetic acid (DTPA), hydroxyethylethylene diamine tri-acetic acid (HEDTA), nitrilotriacetic acid(NTA) (NTA) or diethylene-triamine-pentamethylene phosphonic acid (DTPMPA).

G ₁And G ₂Preferably be C independently of each other ₁-C ₁₈Alkyl, especially C ₁-C ₅Alkyl, the especially tert-butyl group.In preferred formula (1) or (2) chemical compound, G ₁Be positioned at G ₂Between the position.

G ₃Most preferably be hydrogen; C ₁-C ₂₂Alkyl; SO ₃M; By OH and/or by C ₂-C ₂₂The propyl group that alkanoyloxy replaces; Direct key;-CH ₂-;

By OH or C ₂-C ₂₂The propyl group that alkanoyloxy replaces;

Or

Preferred G ₄And G ₅Independent is H or C ₁-C ₄Alkyl, especially methyl.

Technical interested especially be those formula that contains sulfenyl (1) chemical compounds, i.e. G wherein ₁And/or G ₃Be selected from alkylthio group, alkylthio alkyl ,-those of S-.

The chemical compound of preferred use formula (1) and/or (2), especially wherein

A is 1;

B, c, d, e, n, M, q, V be as above definition separately;

If Q exists, then it is-C _mH _2m-and preferred methylene or ethylidene,

If T exists, then it is-C _nH _2n-or phenylene;

G ₃Be hydrogen; C ₁-C ₂₂Alkyl; SO ₃M; By OH and/or by C ₂-C ₂₂The propyl group that alkanoyloxy replaces;

Or G ₃Be direct key;-CH ₂-;

Or by OH or C ₂-C ₂₂The propyl group that alkanoyloxy replaces;

Or G ₃For

Or

G ₄And G ₅Independent is H or C ₁-C ₄Alkyl, especially methyl;

The chemical compound of those formulas (1) most preferably among them, wherein

E is 1 or 2 and G ₃Be SO ₃M; By OH and/or by C ₂-C ₂₂The propyl group that alkanoyloxy replaces;

Or G ₃Be direct key;-CH ₂-;

Or by OH or C ₂-C ₂₂The propyl group that alkanoyloxy replaces; Wherein M is that alkali metal and q are 0 or 1;

Or the chemical compound of formula (2).

Most preferred formula (3) chemical compound has following formula

Or be its acid-addition salts, especially as defined above.

Special compound of interest (1) comprises those of formula (4)

Wherein

G ₁And G ₂Be C independently of one another ₁-C ₅Alkyl or G ₁And G ₂Especially be 2, the 6-di-t-butyl;

A is 1 or 2, especially 1; And

G ₃, Q, V, T, b, c, d and e have the implication of quoting for formula (1), or especially

B be 1 and Q be ethylidene;

C be 1 and V be O or NH;

D be 1 and T be CH ₂Or phenylene; And

E is 1 and G ₃Be H, C ₁-C ₁₈Alkyl such as methyl or C ₁₇Alkyl, or be SO ₃Na; Or

E is 4 and G ₃Be carbon atom;

Or b, c and d respectively do for oneself 0, and e is 2 and G ₃Be methylene or ethylidene.

Most preferred is those of formula (1), especially wherein G ₁And G ₂Be the tert-butyl group; And a is 1.

Also preferably use the chemical compound of following formula

Wherein

G ₁And G ₂Be C independently of one another ₁-C ₅Alkyl;

Q is-C _mH _2m-; Or-c _mH _2m-NH-;

G ₃Be direct key;-O-;-S-;-CH ₂-; Or

A is 1 or 2;

M is 1-5; And

T has the implication of quoting in the formula (1).

Special compound of interest (1) is those, wherein

Q is an ethylidene; Or

G ₃Be direct key; And

G ₁, G ₂, T and a have the implication that provides in the formula (3).

The chemical compound of same preferred following formula

Wherein

Q is-C _mH _2m-;

T is-C _nH _2n-;

G ₁And G ₂Be C independently of one another ₁-C ₅Alkyl;

G _{3 are}Formula (1g); (1h); (1i); Or group (1k);

M and n are 1-3 independently of one another;

A is 1 or 2; And

B and d are 0 or 1 independently of one another.

Other antioxidant that preferably uses meets following formula

Wherein

A is the group of following formula

G ₁, G ₂And G ₃Be C separately independently of one another ₁-C ₅Alkyl; And

M is 1-3.

Other preferred anti-oxidants is those of following formula

Wherein

B is the group of following formula

G ₁And G ₂Be C independently of one another ₁-C ₅Alkyl;

V is-O-; Or-NH-;

A is 1; Or 2;

M is 1-3; And

N is 0-3.

Chemical compound of the present invention, for example formula (1), (2) and (3) chemical compound, previously known is as the antioxidant of plastics and some other organic material.

In the present invention, they can use with independent chemical compound or with the form of mixtures of several individual chemical compound.Because its fine solubility, they can easily mix in each preparation.

Chemical compound of the present invention, for example formula (1), (2), (3) chemical compound also can use with tocopherol and/or tocopheryl acetate, ascorbic acid and/or its derivant or ester, retinal, retinal, tretinoin and/or its derivant.

Other hydrophilic of this class or the contained concentration range of low-polarity component are generally the 0.001%-10% of total formulation weight.Those other compositions are preferably selected from:

--tocopherol (α, beta, gamma, δ isomer) and the ester that forms with following general formula acid thereof

H(CH ₂) _n(CHR)COOH (1)

CH ₃(CH ₂) _mCH＝CH(CH ₂) _nCOOH (2)

Wherein R is hydrogen atom or OH group, and m, n are the integer of 0-22, wherein m+n and be 22 to the maximum;

-tocotrienol (α, beta, gamma, δ isomer). contain a unsaturated aliphatic chain, with and the ester that forms with acid;

-ascorbic acid and the ester that forms with acid as phosphoric acid thereof, and sodium, potassium, lithium and magnesium salt, ascorbyl four different cetylates, other with the ester of 2-pyrrolidone-5-carboxylic acid's formation and with the ester of the acid formation of following general formula

H(CH ₂) _n(CHR)COOH (3)

CH ₃(CH ₂) _mCH＝CH(CH ₂) _nCOOH (4)

Wherein R is hydrogen atom or OH group, and m, n are the integer of 0-20, wherein m+n and be 21 to the maximum;

-retinoid comprises that all have geometric isomer and the stereoisomer of the bioactive natural and/or synthetic vitamin category-A of vitamin A in skin like thing or retinal sample chemical compound and this compounds.Preferred chemical compound is retinal, retinol ester (for example, the C of retinal ₂-C ₂₂Arrcostab (saturated or unsaturated alkyl chain) comprises retinyl palmitate, retinyl acetate, Vitamin A propionate), retinal and/or tretinoin (comprising all trans retinoic acids and/or 13-cis-tretinoin) or derivant.Other retinoid that is used for the present invention is described in US Patent No 4,677,120, Jun.30, and 1987 license to Parish etc.; 4,885,311, Dec.5,1989 license to Parish etc.; 5,049,584, Sep.17,1991 license to Purcell etc.; 5,124,356, Jun.23,1992 license to Purcell etc.Other suitable retinoid is tocopherol retinoic acid ester [Renascin of tretinoin (trans or cis)], adapalene (adapalene) [6-(3-(1-adamantyl)-4-anisyl)-2-naphthoic acid] and tazarotene (6-[2-(4, the 4-dimethyl disulfide is for chromane-6-yl)-acetenyl] ethyl nicotinate);

-carotenoid such as α-, β-, γ-, and δ-carotene, phylloxanthin (lutein), carotenol (xanthophylls), zeaxanthine, violaxanthin, cryptoxanthine, fukoxanthine, antheraxanthin (antheraxanthine), lycopene, two dehydrogenation lycoxanthin and four dehydrogenation lycopene carotenoid

-enzyme antioxidant is as glutathion peroxidase, catalase, erythrocuprein;

-ubiquinone and idebenone (hydroxy decyl ubiquinone), pantothenylol and derivant thereof;

-thioctic acid and derivant thereof such as alpha-lipoic acid;

-rutinic acid and derivant thereof such as alpha-glucosyl rutin, water solublity flavonoid, rutin hydrate (Citrin);

Red autumnal leaves extract, Rhizoma Curcumae Longae L (curcuminoid activating agent), Leontopodium alpinum extract, the Emblica officinalis (phyllanthus emblica) of-plant extract such as Ramulus et Folium Mussaendae Pubescentis and green tea extract, chicory leaf extract (Cichoriumintubybus), Passion flower P.E (maypop), Aspalathus linearis extract, Herba Rosmarini Officinalis extract, maple (Aceraceae Maple tree) or cherry tree (Rosaceae Cherrytree) set extract;

-phenolic acid such as caffeic acid, 3,4-dihydroxyphenyl acetic acid, 3,4-protocatechuic acid;

-flavonoid and polyphenol as flavanone, are selected from unsubstituted flavanone, mono-substituted flavanone and their mixture; Chalcone derivative is selected from and does not replace chalcone derivative, mono-substituted chalcone derivative, dibasic chalcone derivative, trisubstituted chalcone derivative and their mixture; Flavone is selected from and does not replace flavone, single flavone, dibasic flavone and their mixture of replacing; One or more isoflavone; Coumarin is selected from unsubstituted coumarin, mono-substituted coumarin, dibasic coumarin and their mixture; Flavonol, anthocyanin, catechin, proanthocyanidin (Semen Vitis viniferae extract).Can also use and extensively be disclosed in United States Patent (USP) 5,686, the flavonoid in 082 and 5,686,367;

-chlorogenic acid and ferulic acid.

Other type antioxidant of the photochemical reaction chain that causes in the time of also can using interruption to work as ultraviolet rays transdermal or hair.The representative instance of this class antioxidant is aminoacid (for example glycine, histidine, tyrosine, tryptophan) and their derivant; Imidazoles (for example urocanic acid (urocanine acid)) and derivant thereof; Peptide, as D, L-carnosine, D-carnosine, L-carnosine and derivant thereof (for example anserine); Carotenoid, carotene alkene class, lycopene and their derivant; Chlorogenic acid and derivant thereof; Thioctic acid (liponic acid) and derivant (for example dihydrolipoic acid) thereof; Aurothioglucose (aurothioglycose), propylthiouracil and other thiophene sulphur alcohol (for example thioredoxin, glutathion, cysteine, cystine, cystamine and glycosyl thereof, N-acetyl group, methyl, ethyl, propyl group, amyl group, butyl, lauryl, palmityl, oil base, inferior spunyarn base (linoleyl), cholesteryl and glyceryl ester) and salt thereof; Dilauryl thiodipropionate, distearyl thiodipropionate, thio-2 acid and derivant thereof (ester, ether, peptide, lipoid, nucleotide, nucleoside and salt); And sulfo group imines (Sulfoximin) chemical compound, as fourth methyllanthionine sulfo group oxime (buthioninsulfoximine), homocysteine sulfo group oxime (homocysteinsulfoximine), fourth methyllanthionine sulfone (buthioninsulfone), five-, six-, seven methyllanthionine sulfo group oxime (penta-, hexa-, heptathioninsulfoximine); Also have (metal) chelating agen (for example hydroxy fatty acid, Palmic acid, phytic acid, lactoferrin, chitosan and derivant such as phosphonomethyl chitosan) and preferably be disclosed in United States Patent (USP) 5,487,884; WO91/16035; Those of WO91/16034; Hydroxy acid (citric acid for example, lactic acid, malic acid), humic acid, bile acid, bile extract, bilirubin, biliverdin, EDTA, EDDS, EGTA and derivant thereof, unsaturated fatty acid and derivant thereof (linolenic acid for example, linoleic acid, oleic acid), folic acid and derivant thereof, ubiquinone and pantothenylol and their derivant, vitamin C and derivant thereof (for example anti-bad blood acyl cetylate, the ascorbyl magnesium phosphate, the ascorbyl acetate), tocopherol and derivant thereof (for example alpha-tocopherol acetate), the benzoin resin of vitamin A and derivant thereof (for example vitamin A palmitate) and coniferyl benzoate, rutinic acid and derivant thereof, glycosyl rutin, ferulic acid, the furfurylidene glucitol, carnosine, butyl benzene methanol, butylated hydroxyanisole (BHA), nordihydroguaiaretic acid, THBP 2,4,5 trihydroxybutyrophenone, uric acid and derivant thereof, mannose and derivant thereof, erythrocuprein, N-[3-(3,5-di-t-butyl-4-hydroxyphenyl) propionyl] p-anilinesulfonic acid. (and salt, for example this disodium salt), zinc and derivant thereof (ZnO for example, ZnSO4), selenium and derivant thereof (for example selenium methionine), stilbene and derivant thereof (stilbene oxide for example, the trans-stilbene oxide) and described activating agent be suitable for derivant (salt of the present invention, ester, ether, sugar, nucleotide, nucleoside, peptide and lipoid).Can mention HALS (" hindered amine as light stabilizer ") chemical compound in addition.

Other synthetic in addition and natural antioxidant for example is listed among the WO0025731 and lists: structure 1-3 (page 2), structure 4 (the 6th page), structure 5-6 (the 7th page) and chemical compound 7-33 (8-14 page or leaf).

----local application also can contain at least a other composition with antiinflammatory action, is preferably the 0.01%-10% of compositions, more preferably from about 0.5%-is about 5%, as:

The antibiotic medicine of-steroidal includes but not limited to 17-hydroxy-11-dehydrocorticosterone, as hydrocortisone and derivant thereof;

-NSAID (non-steroidal anti-inflammatory drug) includes but not limited to former times health, salycilates, acetogenin, fenamates, propanoic derivatives, pyrazoles;

-natural anti-inflammatory includes but not limited to that the chemical compound in α-bisabolol, allantoin, lyophilizing Aloe extract, pantothenylol, betulinol, the Radix Glycyrrhizae (Glycyrrhiza glabra) comprises that carbenoxalone, glycyrrhizic acid and their derivant (salt and ester) are as sodium glycyrrhetate, dipotaccium glycyrrhizate, ammonium glycyrrhizinate; Allantoxanicacid, its basic salt and alkali salt, boswellic acid, its basic salt and alkali salt, rosmarinic acid (rosemaric acid), its basic salt and alkali salt; Polyunsaturated fatty acid, as linoleic acid (18:2n6), alpha-linolenic acid (18:3n3), gamma-Linolenic acid (18:3n6), parinaric acid (octadekanetetraenic) (18:4n3), dihomo-gamma-linolenic acid (20:3n6), eicosatetraenoic acid (eikosantetraenic) (20:4n3), arachidonic acid (20:4n6), eicosapentaenoic acid (eikosanpentaenic) (20:5n3) acid and the ester that forms with the alcohol of following general formula thereof

R ₁(CH ₂) _m-(CHOH)-(CH ₂) _nR ₂ (5)

R wherein ₁And R ₂Be hydrogen atom or OH group, m, n are the integer of 0-17, wherein m+n and be 21 to the maximum;

The polyethoxylated derivant of phytosterol and following general formula (6) and (7), wherein R is isoalkyl or the different alkenyl with 8-10 carbon atom, wherein n is the integer of 0-50, especially campesterol, cupreol, stigmasterol, cholesterol, △-5-avenasterol, △-7-avenasterol, brassicasterol, chondrillasterol and fucosterol (fukosterol)

Described pharmaceutical composition comprises liquid, semisolid or solid preparation.

The example of composition of liquid medicine is Injectable solution, infusion solution, drop, spray, aerosol, Emulsion, lotion, suspension, drinkable solutions, gargarism and inhalant.

The example of semi-solid medicament compositions is ointment, emulsifiable paste (O/W emulsion), dense (rich) emulsifiable paste (W/O emulsion), gel, lotion, foam, paste, suspension, ovula, plaster (plasters), comprises to use through dermal system such as face shield (masks), compress (compresses), protective pad.

The example of solid composite medicament is tablet, coated tablet, capsule, granule, effervescent granule, effervescent tablet, lozenge, sucking and chewable tablet, suppository, implant, lyophilized products, adsorbate or powder.

Preferred liquid or semi-solid preparation.

The galenical pharmaceutical composition that comprises The compounds of this invention will be understood that especially to refer to emulsion, ointment, gel, spray and powder; For example emulsifiable paste, gel, lotion, alcoholic solution and water/alcoholic solution, emulsion, wax shape/fat composition, strip (stick) preparation such as red lip or deodorizer, powder or ointment.

Cited final preparation can multiple packing specification form exist, for example:

-with form such as W/O, O/W, O/W/O, W/O/W or PIT emulsion and the various microemulsion of liquid preparation,

-with the form of gel,

-with the form of grease, emulsifiable paste, Emulsion or lotion,

-with the form of powder, lacquer, tablet or cosmetics,

-with the rod (stick) form,

-with spray (containing the spray of impelling gas or the spray of pumping action) or aerocolloidal form,

-with the form of foam, or

-with the form of paste,

Advise several microgranules (particulate) skin protection induction system:

A] nanoemulsions (Nanoemulsions) and nanoparticle (nanoparticles) be mainly based on lecithin or fractional distillation phospholipid, especially

Particle size range is the nanoemulsions of 20nm-50nm, is representative with the monofilm, comprises that Nanotopes (surrounded by the film of being made up of phospholipid and cosurfactant by lipid core; Stable and undersized granule (less than liposome) are because the intecalation of the cosurfactant between the lecithin molecules of elongation) and Nanosomes;

-particle size range is the nanoparticle of 100nm-300nm, is representative with the duplicature;

Liposome promptly comprises the spherical vesicles that surrounds core water and form the amphiphilic lipids (mainly being phospholipid) of one or several concentric bilayer; Small unilamellar vesicle (SUV), big unilamellar liposome (LUV), big multilamellar liposome (MLV) or many vesicles (multivesicullar) liposome (MVV)).

For example, The compounds of this invention can mix in the bilayer, in the core water or intersperse among among both.

B] particle diameter the microcapsule of 1 μ m, based on substrate or encapsulation layer (based on the spherical system of the core that contains active component; Examine then by one or several coatings or shell and surround).

The polymer that is used to form those microcapsules comprises natural gum, cellulose components, polysaccharide, synthetic polyacrylate or polyacrylamide, polyvinyl alcohol (PVA), lipoid, inorganic matter (silicate/clay), high-molecular weight albumen such as gelatin, albumin etc.Example comprises that the little porous ball of nylon (Orgasol rangefrom ElfAtochem), mineral filler are as by difunctional overcoat surface-treated sericite (reaction between active derivative of fatty acid and sericite aqueous solution); Glycospheres (based on the nuclear of modified starch with based on the outer lipid membrane of fatty acid and polarity lipoid); CNT; Crepis is made by silicate, be used for non-water with the end capped product of solid as rod, dry powder etc.

C] the matrix granule system, it is capturing activating agent in nuclear matrix uniformly; Example:

-only based on solid lipid nanoparticle (SLN) technology of solid lipid;

-the nano structured lipid carrier (NLC) made by the mixture of solid lipid and liquid fatty (typical particle diameter diameter is within the scope of 80nm-1 μ m);

-millimicro ball (for example US-6491902) is representative with solid hydrophobic and high-cation millimicro ball (typical particle size range is 10nm-1 μ m), and based on the solid hydrophobic substrate with high-cation or bioadhesive layer coating.

D] many walls (Multi-walled) induction system, for example be similar to liposome structure but only by the system of non-phospholipid " analogue membrane " amphiphile preparation, wherein amphiphile such as oleic acid, saturated or unsaturated fatty acid, comprise the aqueous mixtures of amino acid residue, sucrose fatty acid ester, anion surfactant and cationic surfactant with long-chain soap, the derivant of polyglycereol, diammonium amphiphile, cationic surfactant, the cationic amphiphilic thing of tween combination.

E] the microsponge technology is as the system based on microcosmic polymer-type spheroid, and it is made of the interconnected interstices in the non-structure that withers (discontinuous shell); But water expanded granular, cellulose and cellulose derivative that example comprises the copolymer of styrene and divinylbenzene or ethenyl derivatives, made by lactose are as deriving from the Unispheres of Induchem etc.

F] silicone type vesicles, as be similar to the multilamellar vesicles of liposome structure, wherein each layer made by dimethicone cross linked polymer of mixture, dimethicone/vinyl-dimethyl base silicone oil cross linked polymer or the PEG modification of polyether-modified dimethicone (dimethicone copolyol), silicone elastomer, dimethicone cross linked polymer etc.

G] cyclodextrin, be generally the oligomeric and cyclic 6-8 of containing a glucose unit carbohydrate, as α-, β-and gamma-cyclodextrin.

According to preferable methods, chemical compound of the present invention is applied in nano-dispersed dosage form or the encapsulated form, as is described in US-2005-0191330 (especially referring to [0007-0079], [0120-0133] part and embodiment) and US2003-0190347 (especially referring to [0005-0087] part and embodiment).

Other important technically aspect is that discovery chemical compound of the present invention can be protected other activating agent among the present invention, especially easily the natural materials of oxidation or activating agent such as vitamin, plant extract, essence etc.Early stage degraded when protecting most effectively with described composition encapsulation.Therefore chemical compound of the present invention in these cases also is used for pure cosmetic formulations, does not wherein need them that any pharmacology's advantage is arranged, but also seeks for example protection of vitamin such as vitamin A, E or C of other active substance.

The final examples of formulations that contains the present composition also comprises

-skin protectant, as the skin washing and the cleaning formulation of tablet form or liquid soap, soapless detergent or washing paste form (washingpaste),

-shower preparation is as liquid (foam bath, breast, shower preparation) or solid shower preparation, as bathing piece and bath salt;

-skin protectant is as facial treatment milk (skin emulsion), multiple emulsion or skin protection oil (skin oil);

-personal care formulations, as face cosmetic with day cream or Refined Mercurous chloride (powder cream), face powder (loose or compacting), kermes or emulsifiable paste cosmetics form, the eye-care preparation is as eye shadow preparation, mascara, eyeliner, eye cream or fixed eye emulsifiable paste (eye-fix cream); The lip care formulations, as lip pomade, lip gloss (lip contour pencil), lip liner, the manicure preparation is as nial polish, enamel remover, scleronychia agent or horny layer remover;

-foodcare preparation, as foot bath, foot-powder, foot frost or foot face cream (foot balsam), special deodorant and antiperspirant or callus are removed preparation (callus-removing preparation);

-photoprotection preparation, as sunscreen, lotion, emulsifiable paste or oil, sunscreen cream (sunblock) or tropical powder (tropical) shine black preparation in advance or shine the back preparation;

-skin tanning preparation is as shining black frost certainly;

-the preparation that fades (depigmenting preparation), preparation or skin Lightening preparation as bleaching skin is used comprise rinsing preparation such as soap and preparation on skin such as emulsifiable paste etc.;

-dosing soap slab and the liquid that contains antifungal, antibacterial agent etc.

-anthelmintic is as anthelmintic oil, lotion, spray or rod;

-deodorizer is as deodorization spraying, pump sprays, deodorizing gel, rod or walk pearl;

-antiperspirant is as antiperspirant rod, frost or walk pearl;

-be used to clean and nurse the preparation of skin of tarnishing, as synthetic detergent (solid or liquid), peel off or clean preparation or lift off mask;

The depilatory of-chemical form (depilation), as the hair removing powder, liquid depilatory, the depilatory of the emulsifiable paste or the form of paste, the depilatory of gel form or aerosol foam;

-the preparation that shaves, as shaving soap, foaming shave emulsifiable paste, non-foaming shave emulsifiable paste, foam and gel, be used for preparation before the dried palpus that shaves, aftershave lotion or must the back lotion;

-flavoring formulation, as contain spice (cologne (eau de Cologne), beauty water (eau detoilette), fragrance perfume (eau de parfum), cosmetic fragrance (parfum de toilette), spice), aromatic oil or spice emulsifiable paste;

-hair treatment preparation, hair detergent compositions as shampoo and conditioner form, hair care formulations, as the pretreatment preparation, hair oil (hair tonics), moulding emulsifiable paste (styling cream), moulding gel (stylinggels), pomade (pomade), the hair purificant, pack processing, deep agent for treatment of hair, the hair structure chemical preparation, as be used for the hair-waving (burn, temperature is scalded, cold wave) hair-waving preparation, the hair straightening preparation, liquid hair typing preparation, the hair foam, hair sprays, float and send out agent, as hydrogenperoxide steam generator, the light shampoo, the bleaching emulsifiable paste, the bleaching powder, bleaching paste or oil, temporary transient, semipermanent or permanent hair coloring agent comprises the autoxidation dyestuff, or the preparation of natural hair coloring agent such as henna or Flos Chrysanthemi;

The skin preparation of particular importance is daily nursing and/or anti-senile preparation; comprise light protection preparation; as sun-proof Emulsion, lotion, emulsifiable paste, oil, sunscreen cream or topical preparation; Exposure to Sunlight pre-treatment preparation or Exposure to Sunlight post processing preparation; also have the skin tanning preparation, for example desalinate the combination of preparation or this type systematic from tanned emulsifiable paste, skin whitening preparation, skin colour.Interested especially is anti-senile preparation with the UV protection system in combination, as the daily nursing preparation of daily nursing emulsifiable paste, daily nursing lotion, daily nursing Emulsion and spray form.

The additional compounds as described below that also can contain one or more when compositions/preparation according to the present invention is suitable, especially in the skin treatment preparation:

Aliphatic alcohol

Based on the Guerbet alcohol (Guerbetalcohol) of the aliphatic alcohol with 6-18, preferred 8-10 carbon atom, it comprises spermol, stearyl alcohol, cetearyl alcohol, oleyl alcohol, octyldodecanol, C ₁₂-C ₁₅The benzoate of alcohol, Acetylated lanolin alcohols. etc.

Fatty acid ester

Straight chain C ₆-C ₂₄Fatty acid and straight chain C ₃-C ₂₄The ester of alcohol, branching C ₆-C ₁₃Carboxylic acid and straight chain C ₆-C ₂₄The ester of aliphatic alcohol, straight chain C ₆-C ₂₄Fatty acid and branching alcohol be the ester of 2-Ethylhexyl Alcohol especially, hydroxy carboxylic acid and straight chain or branching C ₆-C ₂₂The ester of aliphatic alcohol, malic acid dioctyl ester particularly, straight chain and/or branching fatty acid and polyhydric alcohol are (as propylene glycol, dimer diol or trimer triol) and/or the ester of Guerbet alcohol, as caproic acid, sad, 2 ethyl hexanoic acid, capric acid, lauric acid, different tridecanoic acid, myristic acid, Palmic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, elaidic acid, ocean Fructus Coriandri acid (petroselinicacid), linoleic acid, linolenic acid, eleostearic acid, arachidic acid, gadoleic acid (gadoleic acid), mountain Yu acid and sinapic acid and industrial grade mixture thereof are (for example in the pressure of natural fat and oil removes, in from the reduction of the synthetic aldehyde of Roelen oxidation or in the dimerization of unsaturated fatty acid, obtain), with alcohol as isopropyl alcohol, hexanol, capryl alcohol, 2-Ethylhexyl Alcohol, decanol, lauryl alcohol, different tridecyl alcohol, myristyl alcohol, spermol, Palmitoleyl alcohol (palmoleyl alcohol), stearyl alcohol, isooctadecanol, oleyl alcohol, anti-oleyl alcohol (elaidylalcohol), ocean Fructus Coriandri alcohol (petroselinyl alcohol), inferior oleyl alcohol, linolenyl alcohol, paulownia alcohol, arachidic alcohol, 20 carbon-9-enol (gadoleic acid), behenyl alcohol, the ester of erucyl alcohol and Ba Wei alcohol (brassidyl alcohol) and industrial grade mixture thereof (for example in based on fatty and oily technical grade methyl ester or high-pressure hydrogenation, obtain and obtain) as the monomeric fraction in the unsaturated fatty alcohol dimerization from the synthetic aldehyde of Roelen oxidation.

The example of above-mentioned ester oil is an isopropyl myristate, isopropyl palmitate, isopropyl stearate, the isostearic acid isopropyl ester, acid isopropyl, n-butyl stearate, the just own ester of lauric acid, oleic acid ester in the positive last of the ten Heavenly stems, the different monooctyl ester of stearic acid, stearic acid ester in the different ninth of the ten Heavenly Stems, isononyl isononanoate, Palmic acid 2-ethyl hexyl ester, the own ester of lauric acid 2-, stearic acid 2-hexyl decyl ester, Palmic acid 2-octyl group dodecyl ester, oleic acid oil base ester, erucic acid oil base ester, oleic acid mustard ester (erucyloleate), erucic acid mustard ester, sad cetearyl ester, cetin, the stearic acid cetyl, the oleic acid cetyl, mountain Yu acid cetyl, the acetic acid cetyl, myristyl myristate, mountain Yu acid myristin, the oleic acid myristin, the stearic acid myristin, the Palmic acid myristin, Tetradecyl lactate, propylene glycol dicaprylate/decanoin, the enanthic acid stearyl ester, malic acid two different stearyl esters, octyl hydroxystearate etc.

Other auxiliary agents

α glucityl rutin (CAS No.130603-71-3), o-hydroxybenzoic acid 2-butyl octyl ester (CAS No.190085-41-7), vitamin E (CAS No.1406-18-4), alpha-tocopherol acetate (CAS No.58-95-7), 2,6-naphthalenedicarboxylic acid diethylhexyl ester, Di-n-butyl Adipate, adipic acid two (2-ethyl hexyl ester), succinic acid two (2-ethyl hexyl ester) and two isotridecyl acelaat (diisotridecylacelaat), and binary alcohol esters, as the ethylene glycol bisthioglycolate oleate, the different tridecanoate of ethylene glycol bisthioglycolate, propylene glycol two (2-ethylhexanoate), propylene glycol diisopstearate, propylene glycol dipelargonate, butanediol diisopstearate and neopentyl glycol dicaprylate.C ₆-C ₂₇Aliphatic alcohol and/or Guerbet alcohol and saturated and/or undersaturated aromatic carboxylic acid, especially benzoic ester, C ₂-C ₁₂Dicarboxylic acids with have the straight chain or the branching alcohol of 1-22 carbon atom or have the ester of the polyhydric alcohol of 2-10 carbon atom and 2-6 hydroxyl, or imino-diacetic succinic acid and iminobisuccinate [CAS7408-20-0] or latex particle, Aloe, Flos Chrysanthemi, Semen Ginkgo biloba, Radix Ginseng, coenzyme Q10, laminaria ochroleuca extract, the magnoliaoborata extract, melalenca alternifolia leaf oil, raspberry seed oil, vacciniummacrocarpon seed oil, Semen Cucurbitae extract, pumpkin seed oil, Semen Vitis viniferae extract, carnosine, alpha-arbutin, asiaticoside, termino-laside, tetrahydrocurcuminoids (THC), mycosporines is derived from the mycosporine amino acid of red alga porphyra umbilicalis, mycosporine amino acid (as describing among the WO2002039974), cis-9-octadecene diacid, thioctic acid, Laurel imino-diacetic propanoic acid tocopherol phosphate ester (LDTP), microcrystalline Cellulose (MCC), the Merlon of describing among the WO0341676, the sterol (cholesterol of describing among the WO0341675, lanosterol, plant sterol) and the poly-alpha-glucans of the straight chain of describing among the US6616935.

Natural or the synthetic triglyceride that comprises glyceride and derivant

By with other pure reaction modifyings based on C ₆-C1 ₈The diglyceride of fatty acid or triglyceride (caprylic/capric triglyceride, Fructus Hordei Germinatus glyceride etc.).Polyglycereol (fatty acid ester such as polyglyceryl-4 decanoin of polyglyceryl-n), polyglyceryl-2 isostearate etc., or Oleum Ricini, hydrogenated vegetable oil, Semen pruni armeniacae oil, wheat germ oil (wheat germ oil), Oleum sesami, cotmar, Oleum Cocois, American Avocado Tree oil, Semen Maydis oil, castor oil hydrogenated, Adeps Bovis seu Bubali resin (shea butter), cupu oil, Oleum Glycines, ermine oil (mink oil), Oleum helianthi, safflower oil, macadimia nut oil, olive oil, h-tallow, almond oil, hazelnut oil, borage oil (borago oil) etc.

Comprise long chain acid and the ester of alcohol and wax, as Brazil wax, Cera Flava (white beeswax or Cera Flava), lanolin wax, candelilla wax, ceresine, Japan wax, paraffin, microwax, pure white ceresine, cetearyl ester type waxes (cetearyl esters wax), synthetic bees wax etc. with chemical compound of ceraceous character.In addition, hydrophilic wax such as cetearyl alcohol or partial glyceride.

Pearlescent waxes (Dearlescent wax)

Alkylidene diol ester, especially glycol distearate; Marlamid, especially fatty acid distribution of coconut oil diglycollic amide; Partial glyceride, especially stearic acid monoglyceride; Polyvalent, undersaturated or hydroxyl replaces carboxylic acid and the ester with aliphatic alcohol of 6-22 carbon atom, especially tartaric long-chain ester; Fatty material, for example aliphatic alcohol, aliphatic ketone, fatty aldehyde, fatty ester and aliphatic carbonate ester, it has at least 24 carbon atoms altogether, especially laurone and distearyl ether; Fatty acid, as stearic acid, hydroxy stearic acid or mountain Yu acid, olefin epoxide with 12-22 carbon atom with have the aliphatic alcohol of 12-22 carbon atom and/or have the open-loop products of the polyhydric alcohol of 2-15 carbon atom and 2-10 hydroxyl, with and composition thereof.

Hydrocarbon ils

Mineral oil (lightweight or heavy), vaseline (Yellow Vaselin or white vaseline), microwax, alkanisation compound and isomery alkanisation compound, hydrogenant isomery alkane molecule such as poly decene and polybutene, Parleam, squalane, 2-Methylpentadecane, Fancol ID and other other chemical compounds from plant and animal circle.

Silicones or siloxanes (polysiloxanes of organic replacement)

Dimethyl polysiloxane, methyl phenyl silicone, annular siloxane, and amino-, fatty acid-, alcohol-, polyethers-, epoxy-, fluoro-, glycosides-and/or alkyl-modified silicone compounds, it at room temperature can be liquid or resin form.Linear polysiloxane, dimethyl polysiloxane (Dow Corning200fluid, Rhodia Mirasil DM), dimethyl polysiloxane alcohol, the annular siloxane fluid, D5 (cyclopentasiloxanes) volatile matter (Dow Corning345fluid), phenyl trimethyl polysiloxanes (Dow Corning556fluid).Same suitable is dimethicone, and it is to have the dimethyl polysiloxane of an average chain length 200-300 dimethyl siloxane units and the mixture of hydrogenated silicate.People such as Todd can be in addition at Cosm.Toil.91 to studying in great detail of suitable volatile siloxane, finds in 27 (1976).

Any have straight chain or variable organosilicon polymer or the oligomer of ring-type, side chain or cross-linked structure molecular weight represented in term " silicone ", basically based on multiple construction unit, wherein the silicone atom interconnects (siloxane bond SiOSi) by oxygen atom, and randomly substituted alkyl directly is connected with the silicone atom by carbon atom.

Example comprises:

The cyclosiloxane polymer; The cyclohexyl methyl siloxanes of following general formula

As D5, ring six siloxanes (low viscous volatile fluid; The INCI name that marks concrete ring dimethyl polysiloxane chemical compound is called: cyclotrisiloxane (q.v.) is when n equals 3, cyclotetrasiloxane (q.v.) is when n equals 4, D5 (q.v.) is when n equals 5, encircle six siloxanes (q.v.) when n equals 6 and encircle seven siloxanes (q.v.) when n equals 7);

With the end-blocked linear siloxane polymers polydimethylsiloxane in trimethylsiloxy unit (M unit); The nonpolar liquid of the wide region viscosity of following general formula

Silanol compound or dimethyl silanol, as with general formula with hydroxyl (OH) end capped dimethyl siloxane

(elastomer: moderate is crosslinked, and density allows the prolongation/distortion of molecule, the common polydimethylsiloxane cross linked polymer that does not comprise the PEG modification for the silicone elastomer of the crosslinked acquisition by siloxane structure and resin such as polydimethylsiloxane; Resin: highly cross-linked, density can provide certain rigid for molecule).

Comprise polydimethylsiloxane cross linked polymer in the D5 (for example Dow Corning produce DC9045 silicone elastomer mixture) as the silicone elastomer of coemulsifier system; Polydimethylsiloxane cross linked polymer in the polydimethylsiloxane (for example DC9041 silicone elastomer mixture of Dow Corning production); With the crosslinked polydimethylsiloxanepolymer polymer (q.v.) of C3-C20; Polydimethylsiloxane/vinyl-dimethyl base silicone oil cross linked polymer (DC9506 powder, Dow Corning); Polydimethylsiloxane in the D5/vinyl-dimethyl base silicone oil cross linked polymer (for example SFE839 (GE silicone) or KSG15 (Shin-Etsu));

With the crosslinked dimethyl silicone copolymer of vinyl-dimethyl polysiloxanes.

The resin silicone comprises dispersant such as KP-545 (Shin-Etsu); Polydimethylsiloxanecopolymer copolymer in acrylate/D5; One or more monomeric copolymers in one of polydimethylsiloxane and acrylic acid, methacrylic acid or their simple ester; Siloxysilicates such as trimethylsiloxy silicate; The T-resin; The unitary branched polymer of T-; The Q-resin; The unitary branched polymer of Q-:

Film former and waterproofing agent such as trimethyl silyl oxygen silicate (for example SR399 (GE Silicones) or Wacker-Belsil TMS803 (Wacker Chemie) derive from the mixture of Dow Corning such as DC749 make up fluid (the trimethyl silyl oxygen silicate in the D5) or DC593 fluid (the trimethyl silyl oxygen silicate in the polydimethylsiloxane));

Alkyl-modified siloxanes (AMS), it can improve spreadability and clean resistance or, for example be used for inorganic sunscreen, improve Dispersion of Particles, reduce caking, improve lasting impact to skin.Example:

The alkyl polydimethylsiloxane of following general formula

Wherein R is-(CH ₂) _n-CH ₃

As two phenylpropyl polydimethylsiloxane (SF1555 fluids; The GE silicone);

The alkyl polymethyl siloxane of following general formula

Wherein R is-(CH ₂) _n-CH ₃

Be silicone wax such as the DC2503 wax (Dow Corning) of making up; The octadecyl polydimethylsiloxane

DC2502 fluid (Dow Corning); The cetyl polydimethylsiloxane; DC AMS-C30 wax (Dow Corning); 30-C45 alkyl polymethyl siloxane; DC580 wax (Dow Corning); Stearic oxygen trimethyl silane and stearyl alcohol.

Fluorizated or fluoridized oil

Perflexane, dimethyl cyclohexane, ethyl cyclopentane, poly-whole fluorinated methyl isopropyl ether.

Emulsifying agent

Any emulsifying agent commonly used can be used for described compositions.Emulsifier system for example can comprise: carboxylic acid and salt thereof: the basic soap of sodium, potassium and ammonium, the metallic soap of calcium or magnesium, organic basis soap such as lauric acid, Palmic acid, stearic acid and oleic acid etc.Alkylphosphonic or phosphate ester, acid phosphate, p diethylaminobenzoic acid hydramine, cetyl potassium phosphate.The carboxylic acid of ethoxylation or macrogol ester, the PEG-n acrylate.Straight-chain fatty alcohol with 8-22 carbon atom, its by the 2-30mol ethylene oxide and/or by the 0-5mol propylene oxide with have the alkyl phenol institute branching that has 8-15 carbon atom in the fatty acid of 12-22 carbon atom and the alkyl.Poly alkyl alcohol glycol ethers such as lauryl polyoxyethylene (n) ether, cetearyl polyoxyethylene (n) ether, stearyl polyoxyethylene (n) ether, oil base polyoxyethylene (n) ether.Fatty acid polyglycol glycol ethers such as PEG-n stearate, PEG-n oleate, PEG-n cocos nucifera oil acid esters.Monoglyceride and polyol ester.The C of the addition compound product of 1-30mol ethylene oxide and polyhydric alcohol ₁₂-C22 fatty-acid monoester or diester.Fatty acid and polyglycerin ester such as glyceryl monostearate; two isostearoyl base polyglyceryl-3-diisopstearates; polyglyceryl-3-diisopstearate; triglycerin base diisopstearate, polyglyceryl-2-sesquialter isostearate or the Dimerized thing of polyglyceryl (polyglyceryl dimerates).Mixture from the chemical compound of a plurality of above-mentioned substance kinds also is fit to.Fatty acid polyglycol binary alcohol esters such as monostearate diethylene glycol ester, fatty acid and macrogol ester, fatty acid and sucrose ester such as sucrose ester (sucro esters), glycerol and sucrose ester such as sucrose glyceride.Sorbitol and sorbitan have saturated and the sorbitan monoesters and the diester undersaturated fatty acid and ethylene oxide addition compound product thereof of 6-22 carbon atom.Polysorbate-n series, sorbitan ester such as sesquialter isostearic acid sorbitan ester, PEG-(6)-isostearic acid sorbitan ester, PEG-(10)-sorbitan laurate esters, PEG-17-two oleic acid sorbitan esters.Glucosan derivative, the analog of C8-C22 alkyl list glycosides and oligomeric glycosides and ethoxylation, wherein preferred glucose as sugared composition.O/W emulsifying agent such as methyl glucoside polyoxyethylene (20) ether sesquistearate (methyl gluceth-20 sesquistearate), sorbitan stearate/sucrose cocos nucifera oil acid esters, Glucate SS, cetearyl alcohol/cetearyl alcohol glucoside.W/O emulsifying agent such as methyl glucoside dioleate/methyl glucoside isostearate.Sulfuric ester and sulfonated derivative; the dialkyl sulfosuccinate succinate; the dioctyl succinate; alkyl lauryl sulfonic acid ester; the straight chain sulfonated alkane; sulfonation polypropylene tetramer sulphonic acid ester (sulfonated tetrapro-plyne sulfonate), sodium lauryl sulfate, ammonium lauryl sulfate and lauryl ethanolamine; lauryl ether sulfate; sodium laureth sulfate, sulfosuccinate, the different thiosulfate of acyl group (acylisothionate); alkanolamide sulfate; taurate, methyl tauride, imidazoles sulfate.Amine derivative, amine salt, the amine of ethoxylation has the oxide amine that contains heterocyclic chain, as alkyl imidazoline, pyridine derivate, isoquinolin (isoquinoteines), cetyl pyridinium chloride, cetyl pyridine bromide, quaternary ammonium compound such as cetyl trimethylammonium bromide (CTBA), stearyl alkane ammonium (stearyl alkonium).Amide derivatives, alkanolamide such as amide DEA, the amide of ethoxylation such as PEG-n amide, oxydeamide.Polysiloxanes/poly-alkyl/copolyether and derivant thereof, dimethyl polysiloxane, copolyol, siloxanes polyoxyethylene copolymer, siloxane glycol copolymer.Propenoxylated or POE-n ether (Meroxapols), Polaxamers or poly-(oxygen ethylene) m-block-poly-(oxypropylene) n-block (oxygen ethylene).Have at least one quaternary ammonium group and at least one carboxylate radical and/or sulfonate radical in the zwitterionic surfactant molecule.Particularly suitable zwitterionic surfactant is a betanin; as N-alkyl-N; N-Dimethyl Ammonium glycinate; cocos nucifera oil alkyl dimethyl ammonium glycinate; N-acyl amino propyl group-N; N-Dimethyl Ammonium glycinate; cocos nucifera oil acylamino-propyl-dimethyl ammonium glycinate and 2-alkyl-3-carboxy methyl-3-hydroxyethyl imidazoline; have 8-18 carbon atom in its each comfortable alkyl or the acyl group; and cocoyl amino-ethyl hydroxyethyl carboxyl methylglycine salt; the N-alkyl betaine, N-alkyl amino betanin.Alkyl imidazoline, alkyl peptide (alkylopeptides), lipoamino acid (lipoaminoacides), the alkali of self emulsifying and, A short textbook ofcosmetology, the 8th chapter, table 8-7, the chemical compound of describing in the 250-251 page or leaf at K.F.DePolo.

Nonionic emulsifier such as PEG-6 Cera Flava (with) the PEG-6 stearate (with) polyglyceryl-2-isostearate [Apifac], tristerin (with) the PEG-100 stearate.[Arlacel165], PEG-5 tristerin [arlatone983S], the sorbitan oleate (with) polyglyceryl-3 ricinoleate.[Arlacel1689], sorbitan stearate and sucrose cocos nucifera oil acid esters [arlatone2121], tristerin and lauryl polyoxyethylene (23) ether [Cerasynth945], the pure and mild cetyl polyoxyethylene of cetearyl alcohol (20) ether [Cetomacrogol Wax], pure and mild colysorbate60 of cetearyl alcohol and PEG-150 and stearate-20[Polawax GP200, Polawax NF], the pure and mild cetearyl polyglucoside of cetearyl alcohol [Emulgade PL1618], the pure and mild cetearyl polyoxyethylene of cetearyl alcohol (20) ether [Emulgade1000NI, Cosmowax], the pure and mild PEG-40 Oleum Ricini of cetearyl alcohol [EmulgadeF Special], pure and mild PEG-40 Oleum Ricini of cetearyl alcohol and cetearyl sodium sulfate [Emulgade F], stearyl alcohol and stearyl polyoxyethylene (7) ether and stearyl polyoxyethylene (10) ether [Emulgator E2155], pure and mild stearyl polyoxyethylene (7) ether of cetearyl alcohol and stearyl polyoxyethylene (10) ether [Emulsifyingwax U.S.N.F.], tristerin and PEG-75 stearate [Gelot64], propylene glycol cetyl polyoxyethylene (3) ether acetic acid ester [Hetester PCS], the different cetyl polyoxyethylene of propylene glycol (3) ether acetic acid ester [Hetester PHA], pure and mild cetyl polyoxyethylene (12) ether of cetearyl alcohol and oil base polyoxyethylene (12) ether [Lanbritol Wax N21], PEG-6 stearate and PEG-32 stearate [Tefose1500], PEG-6 stearate and cetyl polyoxyethylene (20) ether and stearyl polyoxyethylene (20) ether [Tefose2000], PEG-6 stearate and cetyl polyoxyethylene (20) ether and tristerin and stearyl polyoxyethylene (20) ether [Tefose2561], tristerin and cetearyl polyoxyethylene (20) ether [Teginacid H, C, X].

Anion emulsifier such as PEG-2 stearate SE, tristerin SE[Monelgine, Cutina KD], propylene glycol stearate [Tegin P], the pure and mild cetearyl sodium sulfate of cetearyl alcohol [Lanette N, Cutina LE, Crodacol GP], the pure and mild sodium lauryl sulfate of cetearyl alcohol [LanetteW], trilaneth-4 phosphate and ethylene glycol stearate and PEG-2 stearate [Sedefos75], tristerin and sodium lauryl sulfate [Teginacid Special].Cation soda acid (cationic acidbases) is as the pure and mild cetrimide of cetearyl alcohol.

The silicone emulsifier that is particularly suitable for W/Si is to meet those of following formula:

Wherein

M is the number of 1-20

N is the number of 0-500

P is the number of 0-50

R ₁Be straight or branched C ₁-C ₃₀Alkyl or phenyl

R ₂For-CCH _2c(O-C ₂H ₄) _a-(O-C ₃H ₆) _b-(O-C ₄H ₈) _d-R ₃

R ₃For-H ,-OH; Straight or branched alkyl C ₁-C ₁₂The straight or branched alkoxy C ₁-C ₆Straight or branched acyloxy C ₂-C ₁₂-NHCH ₂CH ₂COOM; Randomly substituted aminoalkyl on amine functional group;-NHCO (CH ₂) _d-COOM, C ₁-C ₃₀The carboxylic acyl group;

Wherein M is H, Na, K, Li, NH ₄Or organic amine; Randomly substituted phosphono;

-NHCO (CH ₂) _dOH;-NH ₃Y, wherein Y is monovalence organic or inorganic anion such as Cl, Br, sulfate radical, carboxylate radical (acetate, lactate, Radix Citri Limoniae).

A is the number of 0-100

B is the number of 0-50; And

C is the number of 0-5

D is the number of 0-10.

This compounds is represented the organically-modified silicone of oxyalkylene hydrocarbonylation.Other used kind is PEG/PPG polydimethylsiloxane (dimethicone copolyol) or the silicone polyether that clearly illustrates the necessary some surface active property of emulsifying.

The preferred silicone emulsifier of special recommendation meets following formula

Wherein

N is the number of 1-500

R is a straight or branched C1-C30 alkyl or phenyl

R ₂For-CCH _2c(O-C2H ₄) _a-(O-C ₃H ₆) _b-O (C4H ₈) _d-R ₃

R ₃, a, b, c﹠amp; The implication of d is identical with the description of front

Non exhaustive property is enumerated the W/Si emulsifying agent, and is as shown in the table:

The consumption of emulsifying agent can be 1-30 weight %, particularly 4-20 weight % and preferred 5-10 weight % based on the gross weight of described compositions.

When being mixed with the O/W emulsion, the preferable amount of mentioned emulsifier system can account for the 5%-20% of oil phase.

Auxiliary agent and additive

Described cosmetics/pharmaceutical composition, for example white, gel, lotion, alcohol and water/alcoholic solution, emulsion, wax/fat composition, bar-shaped preparation, powder or ointment can comprise gentle surfactant in addition, super superfatting agent, consistency modifiers, thickening agent, polymer, stabilizing agent, bioactive ingredients, the deodorant activities composition, anti-dandruff agent, film former, sweller, further UV light protective agent, antioxidant, hydrotropic solvent (hydrotropic agent), antiseptic, anthelmintic, self-tanning agent, solubilizing agent, aromatic oil, coloring agent, antibacterial etc. are as further auxiliary agent and additive.

Super superfatting agent (super-fatting agents)

The material that is suitable for use as super superfatting agent for example is lanoline and lecithin, and polyethoxylated or acroleic acid esterification lanoline and lecithin derivant, polyol fatty acid ester, monoglyceride and Marlamid, the latter serves as foam stabiliser simultaneously.

Crease-resistant activating agent

Preparation of the present invention can further comprise suitable anti-wrinkle agent, comprises D and L aminoacid and derivant and salt, especially the N-acetyl derivative of sulfur-bearing, and wherein preferred examples is N-acetyl group-L-cysteine; Sulfur alcohol; Hydroxy acid (salicylic acid, glycolic), keto acid (acetone acid), phytic acid, thioctic acid; Lysophosphatidic acid (lysophophatidic acid), the skin peeling agent, flavonoid, stilbene, cinnamate, resveratrol, kijnetin, zeatin, dimethylaminoethanol, the peptide in natural and synthetic source, sugar lime (managanese gluconate), terpenol, compound vitamin B such as vitamin B3, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B5 (pantothenic acid), vitamin B t (carnitine), vitamin B12 (cobalamine), VITAMIN B15 (pangamic acid or DIEDI) and derivative salt thereof.Inhibitors of metalloproteinase, trace element and trace element-complex are as containing the peptide of Cu, Zn, Mn, Co, Mg or Se.

Skin lightening agent (Skin lighteningagents)

Preparation of the present invention can further comprise suitable skin lightening composition, comprises kojic acid, arbutin, tranamic acid, ascorbic acid and derivant thereof, for example, and ascorbyl magnesium phosphate or ascorbyl sodium phosphate or other ascorbic acid based phosphates.Those compositions of listing among the PCT application No US95/02809 that also has the PCT application NoUS95/07432 that submits to February 24 nineteen ninety-five and submit to January 3 nineteen ninety-five.

Surfactant

The gentle surfactant that is fit to; that is to say the surfactant of accepting for skin particularly well; the example comprises poly alkyl alcohol glycol ethers sulfate, monoglyceride sulfate, monoalkyl and/or dialkyl sulfosuccinates, fatty acid isethionate, fatty acid sarcosinate, fatty acid tauryl amine, fatty acid glutamate, Glu, alpha-alkene sulfonate, ether carboxylic acid, oligomeric alkyl glucoside, fatty acid glucamide, alkyl amido betanin and/or protein fatty acid condensation product, and the latter is preferably based on aleuronat.

Consistency modifiers/thickening agent and rheology modifier

Silicon dioxide, magnesium silicate, aluminium silicate, polysaccharide or derivatives thereof such as hyaluronic acid, xanthan gum, guar gum, agar, alginate, carrageenin (carraghenan), gellan (gellan), pectin, or modified cellulose such as hydroxylated cellulose, hydroxypropyl emthylcellulose.The homopolymer and the polyacrylamide of polyacrylate or netted acrylic acid (reticulated acrylic acid) in addition, carbomer (carbomer) (carbopol types980,981,1382, ETD2001, ETD2020, UltreZ ₁O) or Salcare series as Salcare SC80 (stearyl polyoxyethylene (10) ether allyl ether/acrylate copolymer); Salcare SC81 (acrylate copolymer); Salcare SC91 and Salcare AST (sodium acrylate copolymer/PPG-1 tridecyl polyoxyethylene (6) ether); sepigel305 (polyacrylamide/lauryl polyoxyethylene (7) ether); Simulgel NS and Simulgel EG (Hydroxyethyl Acrylate/acryloyl group dimethyl sodium taurocholate copolymer); Stabilen30 (acrylate/isodecyl acid vinyl esters cross linked polymer); Pemulen TR-1 (acrylate/acrylic acid C10-30 alkyl ester cross-linked polymer); Luvigel EM (sodium acrylate copolymer), Aculyn28 (acrylate/behenyl alcohol polyoxyethylene (25) ether metacrylic acid ester copolymer) etc.

Viscosity additive is set up network structure in whole base fluid, show as " plastic yield ".Clay and polymeric additive have high plastic yield, therefore are used for positivity support suspension problem.About particle suspending, add this class viscosity build agent and will help to reduce density contrast between granule and the surrounding fluid medium, therefore will produce opposing preferably to particulate sedimentation.

Thickening agent can be divided at least 2 kinds of total classifications: in water, show top performance those and in oil, show those of top performance.

In addition, also can distinguish, for example synthetic polymer, natural polymer and its derivant, mineral polymer etc. according to its character.But also can distinguish, as anion, cation, nonionic or both sexes according to its ion characteristic.

Polymer

The cationic polymer that is fit to for example is a cationic cellulose derivative, as the quaternized hydroxy methocel that can obtain from Amerchol with title Polymer JR400, cationic starch, the copolymer of diallyl ammonium salt and acrylamide, quaternized vinyl pyrrolidone/vinyl imidazole polymer, for example

(BASF), the condensation product of polyglycols and amine, quaternized collagen polypeptide is as lauryl dimethyl ammonium hydroxypropyl hydrolytic collagen

/ Gr ü nau), quaternized Semen Tritici aestivi polypeptide, polymine, the cationic silicone polymer, as the acylamino-methyl polysiloxane, the copolymer (Cartaretin/Sandoz) of adipic acid and dimethylamino hydroxypropyl diethylenetriamines, the copolymer of acrylic acid and dimethyl diallyl ammonium chloride (Merquat550/Chemviron), poly-amino polyamide, as in FR-A-2252840, describing, and the cross-linked, water-soluble polymer, the cation chitin derivatives, as quaternised chitosan, it randomly distributes as crystallite; The condensation product of saturated dihalide such as dibromobutane and two dialkylamines, for example two dimethylaminos-1,3-propane, cation guar gum, as Jaguar C-17, Jaguar C-16 from Celanese, QAS polymer is as Mirapol A-15, Mirapol AD-1, the Mirapol AZ-1 from Miranol.As for anion, amphion, both sexes and non-ionic polymers are for example considered vinyl acetate/.beta.-methylacrylic acid copolymer, vinyl pyrrolidone/vinyl acrylate copolymer, vinyl acetate/maleic acid butyl ester/isobornyl acrylate copolymer, methyl vinyl ether/copolymer-maleic anhydride and ester thereof, uncrosslinked polyacrylic acid and with the polyacrylic acid of polyol crosslink, acrylamido propyl group-trimethyl ammonium chloride/acrylate copolymer, octyl acrylamide/methyl methacrylate/t-butylaminoethyl methacrylate/methacrylic acid 2-hydroxypropyl ester copolymer, polyvinyl pyrrolidone, vinyl pyrrolidone/vinyl acetate copolymer, vinyl pyrrolidone/dimethylaminoethyl acrylate methyl base amino-ethyl ester/caprolactam terpolymer and optional deutero-cellulose ether and siloxanes.Can use in addition at the polymer described in the EP1093796 (3-8 page or leaf, 17-68 section).

Bioactive ingredients

Bioactive ingredients is interpreted as for example referring to vitamin E, alpha-tocopherol acetate, Palmic acid vitamin E, ascorbic acid, DNA (deoxyribonucleic acid), retinol, bisabolol (bisabolol), allantoin, phytantriol, panthenol, AHA acid, aminoacid, ceramide, analog neuron amide (pseudoceramide), quintessence oil, plant extract and vitamin coordination compound.

The deodorant activities composition

As for the deodorant activities composition, for example consider antiperspirant, as aluminum chloride hydrate (referring to J.Soc.Cosm.Chem.24,281 (1973)).Trade mark with Hoechst AG

, for example can buy a kind of corresponding to formula Al ₂(OH) ₅Cl * 2.5H ₂The aluminum chloride hydrate of O, its use are particularly preferred (referring to J.Pharm.Pharmacol.26,531 (1975)).Except chloride hydrate (chlorohydrate), also can use hydroxyacetic acid aluminum and acidic aluminum/zirconates.Esterase inhibitor can be used as other deodorant activities compositions and adds.Described inhibitor is the citric trialkyl ester preferably, as citric acid trimethyl ester, citric acid tripropyl ester, citric acid triisopropyl ester, citric acid tributyl ester and particularly citric acid triethyl group ester (Hydagen CAT, Henkel), its inhibitory enzyme activity and therefore reduce abnormal smells from the patient and form.Other materials that are considered as esterase inhibitor are sterol sulfate or phosphate, the for example sulfate or the phosphate of lanosterol, cholesterol, campesterol (campesterol), stigmasterol (stigmasterol) and sitosterol (sitosterol), dicarboxylic acids and ester thereof, for example 1,3-propanedicarboxylic acid, 1,3-propanedicarboxylic acid mono ethyl ester, ethyl glutarate, adipic acid, monoethyl adipatee, diethylene adipate, malonic acid and diethyl malonate and hydroxy carboxylic acid and ester thereof, for example citric acid, malic acid, tartaric acid or diethyl tartrate..The antibacterial activity composition that influences microorganism species and kill the antiperspirant decomposing bacteria or suppress its growth may reside in (especially in bar-shaped preparation) in the described preparation equally.The example comprises chitosan, phenyl phenol and chlorhexidine gluconate (chlorhexidine gluconate).5-chloro-2-(2, the 4-dichlorophenoxy)-phenol (Triclosan, Irgasan, Ciba Specialty Chemicals Inc.) is also verified effective especially.

Anti-dandruff agent

As for anti-dandruff agent, for example can use Climbazole (climbazole), Octopirox (octopirox) and vancide ZP (zinc pyrithione).Conventional film former for example comprises chitosan, crystallite chitosan, n-trimethyl chitosan chloride, polyvinyl pyrrolidone, vinyl pyrrolidone/vinyl acetate copolymer, comprises polymer, collagen, hyaluronic acid and salt thereof and the similar compound of acrylic acid quaternized cellulose at high proportion.

Hydrotropic solvent

In order to improve flowing property, also can adopt hydrotropic solvent, monohydric alcohol, dihydroxylic alcohols or the polyhydric alcohol that carbon number for example ethoxylation or non-ethoxylatedization is less or its ether (as ethanol, isopropyl alcohol, 1,2-two propane glycol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monomethyl ether, ethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol list ethylether, propylene glycol single-butyl ether, diglycol monotertiary methyl ether, carbiphene, diglycol monotertiary butyl ether and similar products).The polyhydric alcohol of for this reason considering preferably has 2-15 carbon atom and at least 2 hydroxyls.Described polyhydric alcohol also can contain other functional groups, and is especially amino, and/or can be by the nitrogen modification.Representative instance is as follows: glycerol, and aklylene glycol is as ethylene glycol, diethylene glycol, propylene glycol, butanediol, hexanediol and Polyethylene Glycol with the daltonian mean molecule quantity of 100-1000; The oligomeric glycerol mixture of technical grade with intrinsic condensation degree (intrinsic degree ofcondensation) of 1.5-10 for example has technical grade two glycerol mixtures of 40-50 weight % two glycerol contents; Methylol compound, for example especially trimethylolethane, trimethylolpropane, tri hydroxy methyl butane, tetramethylolmethane and dipentaerythritol; Low alkyl group-glucoside especially has those of 1-8 carbon atom, for example methyl and butyl glucoside in moieties; Sugar alcohol with 5-12 carbon atom, for example Sorbitol or mannitol; Sugar with 5-12 carbon atom, for example glucose or sucrose; Amino sugar is as glycosamine; Glycol amine is as diethanolamine or 2-amino-1, ammediol.

Antiseptic and antibacterial

The antiseptic that is fit to for example comprises methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, alkyldimethylbenzylammonium chloride, 2-bromo-2-nitropropane-1, the 3-glycol, dehydroactic acid, diazolidinyl urea (Diazolidinyl Urea), 2-two chloro-benzylalcohols, DMDM Hydantoin, formalin, methyl dibromo glutaronitrile (Methyldibromoglutanitrile), phenyl phenol, sodium hydroxy methyl glycinate, imidazolidinyl urea (Imidazolidinyl Urea), triclosan (Triclosan) and listing in: K.F.DePolo-A short textbook ofcosmetology, the 7th chapter below with reference to other material classifications in the document, table 7-2,7-3,7-4 and 7-5, the 210-219 page or leaf.

Antibacterial

The representative instance of antibacterial is the antiseptic that gram-positive bacterium is had specific function, as 2,4, and 4 '-three chloro-2 '-hydroxy diphenyl ether, chlohexidine (1,6-two (4-chlorphenyl-two guanidine radicals) hexane) or TCC (3,4,4 '-trichlorine carbanilide).A large amount of aromatic compounds and ether oil also have antimicrobial properties.Representative instance is active component acetaminol, menthol and the thymol in Oleum Caryophylli, Oleum menthae and the thyme oil.The natural deodorant of paying close attention to be present in terpenol farnesol in the Lay lemon caul-fat (3,7,11-trimethyl-2,6,10-dodecane triolefin-1-alcohol (3,7,11-trimethyl-2,6,10-dodecatrien-1-ol)).Glyceryl monolaurate also is proved to be a kind of antibacterial.The consumption of existing other antibacterial is 0.1-2 weight % based on the solids content of described preparation usually.

Aromatic oil

The mixture of natural and/or synthetic aromatic substances for example is the extract of following material: flower (Bulbus Lilii (lilies), Garden lavender (lavender), Flos Rosae Rugosae (roses), jasmine (jasmine), orange blossom (neroli), smooth blue (ylang-ylang)), stem and leaf (Flos Pelargonii (geranium), patchouli (patchouli), Folium citri sinensis (petitgrain)), fruit (Pimpinella anisum Linn. (aniseed), Herba Coriandri (coriander), Fructus cari carvi (caraway), juniper (juniper)), fruit skin (bergamot (bergamot), Fructus Citri Limoniae (lemons), Fructus Citri junoris (oranges)), root (Semen Myristicae (mace), Radix Angelicae Sinensis (angelica), Herba Apii graveolentis (celery), Elettaria cardamomum (L.) Maton (cardamom), the Radix Aucklandiae (costus), orrisroot (iris), Rhizoma Acori Graminei (calmus)), timber (Masson Pine (pinewood), sandalwood (sandalwood), guaiaci lignum (guaiacum wood), Lignum seu Ramulus Cunninghamiae Lanceolatae (cedarwood), rose wood (rosewood)), draft and dogstail (tarragon (tarragon), Herba Cymbopogonis Citrari (lemon grass), Salvia japonica Thunb. (sage), Herba thymi vulgaris (thyme)), needle and withe (PiceameyeriRehd. Et Wils. (spruce), pinaster (pine), Lapland pine (Scots pine), high mountain Dacrydium pierrei (mountainpine)), resin and face cream (ancient paulin face cream (galbanum), Canarium luzonicum Elemi (elemi), Benzoinum (benzoin), poponax resin (myrrh), Olibanum (olibanum), family group photo (opoponax)).Also can consider animal material, as Zibethum and castoreum.Typical synthesis of aromatic material for example is ester, ether, aldehyde, ketone, alcohol or hydrocarbon product.The aromatic substances chemical compound of esters for example be acetic acid benzyl ester, phenoxyethyl isobutanoate, acetic acid right-tert-butylcyclohexyl ester, linalyl acetate, acetic acid dimethyl benzyl methyl ester, ethyl phenyl acetate, benzoic acid in any ester, formic acid benzyl ester, glycine ethyl methyl phenyl ester, propanoic acid pi-allyl cyclohexyl ester, styralyl propionate (styrallyl propionate) and salicylic acid benzyl ester.Described ether for example comprises benzylisoeugenol; Described aldehyde for example comprises blue aldehyde (lilial) of straight chain alkanal, citral, citronellal, citronellyl oxygen acetaldehyde (citronellyl oxyacetaldehyde), cyclamen aldehyde (cyclamenaldehyde), hydroxycitronellal (hydroxycitronellal), the tinkling of pieces of jade and the bourbonal (bourgeonal) with 8-18 hydrocarbon atom; Described ketone for example comprises ionoionone, isomethyl ionone and methyl cedrone (methyl cedryl ketone); Described alcohol for example comprises anethole (anethol), citronellol, acetaminol, isoeugenol, geraniol, linalool, the pure and mild terpinol of phenylethyl (terpinol); And described hydrocarbon mainly comprises terpenes and face cream.Yet, the preferred mixture that uses the multiple aromatic substances of the attractive fragrance of common generation.The main ether oil that is used as the relative low volatility of aromatised fraction also is suitable for as aromatic oil, as sage oil, chamomile oil, Oleum Caryophylli, melissa oil, Cortex Cinnamomi leaf oil, Lay lemon caul-fat (limeblossom oil), oleum juniperi e baccarae, vetiver oil, Olibanum oil, ancient paulin face cream oil, lily feet caul-fat and lavandin oil.Independent or the mutual blended oleum bergamottae of preferred use, dihydromyrcenol, the blue aldehyde of the tinkling of pieces of jade, the blue aldehyde (lyral) of the new tinkling of pieces of jade, citronellol, phenylethyl alcohol, jasminolene, geraniol, benzylacetone, cyclamen aldehyde, linalool, methoxy methyl basic ring dodecyl ether (boisambrene) forte, dragon saliva furan (ambroxan), indole, MDJ, sandelice, Fructus Citri Limoniae oil, tangerine oil, orange oil, pi-allyl amyl group ethyl glycolate, cyclovertal, lavandin oil, muscadine sage oil, damascone, bourbon's wine Flos Pelargonii oil, the salicylic acid cyclohexyl ester, vertofix coeur top grade (vertofix coeur), iso-E-Super, Fixolide NP, synthetic oak moss (evernyl), methyl ionone γ, phenylacetic acid, geranyl acetate, benzyl acetate, the Flos Rosae Rugosae oxide, romillat, irotyl and floramat.

Other auxiliary agents

Described cosmetic formulations can comprise defoamer such as the siloxanes as auxiliary agent in addition, structural agent (structurants) is as maleic acid, solubilizing agent such as ethylene glycol, propylene glycol, glycerol or diethylene glycol, opacifier such as latex, styrene/PVP or styrene/acrylamide copolymer, propellant such as propane/butane mix, N ₂O, dimethyl ether, CO ₂, N ₂Or air, as the so-called coupling agent and the developer component of oxidation dye precursors, Reducing agent such as thioglycolic acid and derivant thereof, 2-mercaptopropionic acid, cysteamine, mercaptosuccinic acid. or ethane thiol sulfonic acid, or oxidant such as hydrogen peroxide, Potassium bromate. or sodium bromate.

The anthelmintic that is fit to for example is N, the N-diethyl--toluamide, 1,2-pentanediol or anthelmintic 3535; The self-tanning agent that is fit to for example is dihydroxy acetone and/or Erythrulose or dihydroxy acetone and/or dihydroxyacetone precursor (as describing in WO01/85124) and/or Erythrulose.

Pigment

Can use suitable and permission cosmetics desired substance as pigment, for example edit and record in publication " Kosmetische

" of the Farbstoffkommission der DeutschenForschungsgemeinschaft, Verlag Chemie, Weinheim, 1984, those among the pages81to106.This class pigment uses with the concentration based on the 0.001-0.1% weight of total mixture usually.

Other auxiliary agents

Defoamer such as siloxanes, structural agent (structurants) is as maleic acid, solubilizing agent such as ethylene glycol, propylene glycol, glycerol or diethylene glycol, opacifier such as latex, styrene/PVP or styrene/acrylamide copolymer, chelating agent such as EDTA, NTA, alanine oxalic acid (alaninediacetic acid) or phosphonic acids, propellant such as propane/butane mix, N ₂O, dimethyl ether, CO ₂, N ₂Or air, as the so-called coupling agent and the developer component of oxidation dye precursors, Reducing agent such as thioglycolic acid and derivant thereof, 2-mercaptopropionic acid, cysteamine, mercaptosuccinic acid. or ethane thiol sulfonic acid, or oxidant such as hydrogen peroxide, Potassium bromate. or sodium bromate.

The anthelmintic that is fit to for example is N, the N-diethyl--toluamide, 1,2-pentanediol or anthelmintic 3535; The self-tanning agent that is fit to for example is dihydroxy acetone and/or Erythrulose or dihydroxy acetone and/or dihydroxyacetone precursor (as describing in WO01/85124) and/or Erythrulose.

The beadlet of polymer or hollow ball can be used as the SPF reinforcing agent.

Chemical compound of the present invention, those of formula (1), (2) and/or (3) for example, also be contained in the liposome or use, wherein for example carbamide, dextran, propylene glycol, oleic acid or the like of penetration enhancers with the pharmaceutical compositions that contains conventional carrier and penetration enhancers.

The amount that pharmaceutical composition contains chemical compound of the present invention is generally the 0.001-10% weight of total mixture, preferred 0.01-5%, especially 0.01-2% weight.In order to treat the disease of above enumerating; except that The compounds of this invention; pharmaceutical composition of the present invention also can contain other medicine that for example has antiphlogistic activity or cosmetic agent, generally includes antiinflammatory, vitamin and/or antipsoriatic (suitably time), other skin active agent, cell proliferation regulator, antiallergic agent, UV protective agent, humidizer, antidotal agent, gastric protective agent, antiasthmatics, DNA protective agent.

Pharmaceutical composition of the present invention can contain antioxidant and/or light stabilizer except that formula of the present invention (1)-(3), especially the UV absorbent.The suitable composition of this class material comprises those that describe among EP-A-955355, WO00/25730, WO00/25731, WO03/103622, the EP-A-1366763.

Example is a following ingredients:

As moisture and butyraceous emulsion (W/O for example, O/W, O/W/O and W/O/W Emulsion or microemulsion), this class preparation contains, for example, based on the 0.1-30% weight of compositions gross weight, preferred 0.1-15% weight and one or more UV absorbent of 0.5-10% weight especially; At least a oil component (oilcomponent) based on the 1-60% weight of compositions gross weight, especially 5-50% weight and preferred 10-35% weight; At least a emulsifying agent based on the 0-30% weight of compositions gross weight, especially 1-30% weight and preferred 4-20% weight; Based on the 10-90% weight of compositions gross weight, the water of 30-90% weight especially; And 0-88.9% weight, other acceptable adjuvant of making up of 1-50% weight especially.

Cosmetics or pharmaceutical preparation generally can for example be stirred by each composition together simply by active component and adjuvant are prepared with the conventional method physical mixed.

Useful especially in the present invention examples for compounds comprises following those:

AO3: the product of glycerol, Oleum Cocois and following formula: compound

(mixture of monoglyceride, diglyceride and the triglyceride of β-(3,5-di-t-butyl-4-hydroxyphenyl) propanoic acid and fatty acid, CAS Reg.No.179986-09-5)

AO5 is the mixture of following formula: compound:

AO7: tetramethylolmethane-four (3-[3 ', 5 '-di-t-butyl-4 '-hydroxyphenyl]-propionic ester).

Citrate.

Following examples will be used for illustrating the present invention rather than meaning has any restriction to wherein described.Unless otherwise, percentages.Abbreviation:

The DMSO dimethyl sulfoxide

The EDTA ethylenediaminetetraacetic acid

The ELISA enzyme-linked immunosorbent assay

The FCS hyclone

Embodiment 1: cytotoxicity

Cell culture: primary human dermis fibroblast (HDF-N2) is remained on DulbeccoShi culture medium (DMEM; The 1g/L glucose) in, be supplemented with 10% hyclone (FCS), the streptomycin sulfate of 100 μ g/mL, the penicillin of 100U/ml and the L-glutaminate of 2mM, they all derive from Biowhitaker, USA.With fused cell by in 0.055 trypsin/0.53mM EDTA, separating in 3 minutes in 37 ℃ of incubations, the cell density (usually, 15 * 10 to determine then ⁴Cell/cm ²) bed board.

The test: with each test compounds (active substance) in DMSO or the stock solution in ethanol (5%) be diluted to (referring to top) in the cell culture medium that contains 10%FCS, as shown in table 1.The culture medium of negative control contains 10mMol NaCl or 0.05%DMSO or 0.05% ethanol respectively.Positive control is for containing the culture medium of 0.02% sodium lauryl sulfate (SDS).

For relatively, used identical dilution other culture medium that contains following formula: compound.

(contrast)

For adding thus obtained test medium in the 24h-48h culture fluid of above-mentioned human dermis fibroblast (HDF), measure survival rate (at OD by the specific stain label that only is penetrated in the living cells ₄₅₀Absorb manyly more, then living cells is many more: the dermal fibroblast of living has the esterase that discharges color, and its absorbing wavelength is 450nm.And dead cell can not.In the presence of substances, measure the OD450 in the cell culture medium, and itself and untreated comparing are obtained Cytotoxic measurement result thus).

Editor is in following table as a result.

Absorbance (OD450) after table 1:24h handles

The cytotoxicity of test compounds of the present invention within the acceptable range.

Embodiment 2: anti-inflammatory activity (external)

Pass through to change basic PGE among the HDF-N2 according to the description among the embodiment 1 ₂The ability that discharges, thereby the anti-inflammatory activity of test compounds.

For this reason, cell was cultivated 3 days in 24 well culture plates.Before handling fused cell, stop 24h, handle 18-24h with the test compounds of selected concentration then with the culture medium that contains 1%FCS.Each test compounds AO3, AO5, AO6 and AO7 use with 1:500,1:1000 and 1:1500 dilution factor respectively, join in the culture medium by the stock solution that will describe among an amount of embodiment 1 separately to prepare.

After the processing, remove cell conditioned medium liquid and, derive from the ELISA test kit analysis PGE of Amersham Biosciences up to utilization aliquot storage under-20 ℃ ₂With PGE ₂Value (pg/ hole) is proofreaied and correct with whole protein (measuring by BCA method (pierce)) respectively and with PGE ₂(pg/mg albumen or ng/mg albumen) expression.

Carry out the morphology contrast during 24h that product used by phase contrast microscopy (phase constrast microscopy).

The result: test compounds shows good PGE ₂Suppress active.

Embodiment 3: estimate that photooxidation should in the skin that the The compounds of this invention antagonism brought out by the UVA irradiation Swash reaction(Photooxidative Stress) Effectiveness

Reduce antioxidant activity in the ability measurement body of the lipid peroxidation that free radical brings out by test compounds.

Experimenter: 10 individualities (4 woman, 6 men); The range of age: 18-32 year

The body region of test: inboard forearm

Use phase: once a day

7 days experimental periods

Evaluation methodology :-mensuration Squalene

Evaluation methodology :-mensuration Squalene hydroperoxides

Evaluation time: after the UVA irradiation

Estimate: descriptive statistics: meansigma methods, intermediate value, minima, maximum, difference, standard error, standard deviation; The multipass method of inspection.

Test method

Each test compounds (active substance) is used with the alcoholic solution of 1%b.w, except that AO7 uses with the alcoholic solution of 0.1%b.w.; These test solutions are also referred to as preparation hereinafter.On the inboard forearm of each experimenter, delimit relative symmetrically position.Each preparation is once a day with about 2mg test solution/cm ²Dosage use a week (use with syringe for fine doses: -F1ml; Manufacturer: BraunMelsungen AG, Germany).

Two zones keep being untreated.

The alcoholic solution of tocopherol (0,2%) was used in contrast separately before irradiation.

Use with other cosmetic product in the whole research is limited in the test position.

Then with (10 joules/cm of UVA light ²) (exception: irradiation is not accepted in one of two untreated zones, may shine owing to the UVA of duration of test environment) shone in the zone at experimenter back.Lipid by the existence of solvent extraction (4ml ethanol 2 minutes) acquisition test zone.At first sample is filtered with decantation squama (squame) and other insoluble substance by the hydrophobic polypropylene filter, under nitrogen, absorb then in drying at room temperature and with 1ml ethanol.By high performance liquid chromatography (HPLC) Squalene (SQ) and Squalene hydroperoxides (SQOOH) are analyzed then.

The result uses with respect to the suppression ratio of untreated areas and represents:

% inhibition=100x[SQOOH (untreated)-SQOOH (activating agent)]/SQOOH (untreated)

(p mole SQOOH/pg Squalene in the hydrogen peroxide)

The HPLC of SQ analyzes

Post:

100RP-18 (5 μ m, 125x4mm) Merck-Germany

Mobile phase: acetonitrile/isopropyl alcohol (1/1; V/v)

Detect: UV210nm

Flow velocity: 1ml/min

Volume injected: 20 μ l

Equipment: Beckman System Gold (USA) with Programmable Solvent Module126and Programmable Detector Module166

The HPLC of SQOOH analyzes

Post:

100RP-Select B (5 μ m, 125x4mm) Merck-Germany

Mobile phase: methanol

Detect: chemiluminescence (detecting behind the post)

Flow velocity: 1ml/min

Volume injected: 20 μ l

Reaction solution: 3-luminol (1mg/ml) and cytochrome C (10mg/ml is dissolved in pH10 borate-buffer of 50mM)

Equipment: Beckman System Gold (USA) with Programmable SolventModule126and fluorometer RF-551 (Shimadzu, Japan)

Exometer is used as photon detector, and excitation source is closed.

This detection is measured hydroperoxy-group itself rather than is indicated lipid peroxidation indirectly such as the catabolite of conjugated diene or lipid hydroperoxide.Chemiluminescence also detects pantothenylol.Cause owing to hydroperoxides rather than hydroquinone in order to ensure any chemiluminescence of in this detection, being observed, with some samples with the triphenyl phasphine reduction and then carry out.Because the chemiluminescence reaction of hydroperoxides rather than hydroquinone is eliminated by triphenyl phasphine, handle chemiluminescence that the disappearance indication at sample chemiluminescence peak observed and cause in this detection owing to hydroperoxides rather than hydroquinone.

The biostatistics

In validity check with after the quality assurance, measurement data is carried out center calculation handle.With being suitable for Windows, 5.0 editions-Manugistics, the Statgraphics software of USA is estimated.Data are passed through multipass method of inspection (LSD: least significant difference) analyze.The level of selection 0.05 is accepted the point of statistical significance as minimum.

The result

With the radiating untreated control of UV, compare significantly (p＜0.05) minimizing Squalene peroxidating of skin care formulation of the present invention.

In untreated not irradiation area, do not detect the formation of the extractible Squalene hydroperoxides of ethanol.

The average inhibition of representing with snperoxiaized % is

Preparation	Suppress
		AO4	28％
AO5	26.5％
		AO6	28％
AO7	21.5％
		AO8	21％
Contrast	22.5％

Conclusion:

Epidermal surface had significantly reduced the sebum peroxidating that UV brings out with preparation pretreatment of the present invention before being exposed to the UVA irradiation.These researchs provide strong evidence for the free radical hypothesis of the photo-induced dermal pathology of UVA: lipid peroxidation increases when irradiation, and the local application antioxidant system prevents this damage.

Embodiment 3: skin preparation

General preparation:

Obtain transparent homogeneous phase precursor (prephase) by mixing following composition:

(a) phospholipid of 5-20% weight (for example lecithin),

(b) coemulsifier of 15-40% weight (for example sulfate hemiester of polyethoxylated sorbitan fatty ester, polyethoxylated aliphatic alcohol, polyethoxy fatty acid, polyethoxylated vitamin e derivative, polyethoxylated lanoline or lanolin derivative, polyethoxy fatty glyceride or partial glyceride, polyethoxylated alkyl phenol, polyethoxylated aliphatic alcohol or its salt, polyethoxylated fatty amine or amide, polyethoxylated carbohydrate)

(c) low-polarity component of 30-70% weight, form by triglyceride, chemical compound of the present invention such as AO3-AO8 and other optional activating agent, wherein activating agent: the weight ratio of triglyceride be generally 1:5 to 5:1 and

(d) alcohol of 3-30% weight, as ethanol,

Wherein composition (a) and (b), (c) and percentage ratio summation (d) add to 100%,

With

The liquid that obtains is joined aqueous phase.(for example 90kg) inserts in the container at 50 ℃ with water, stirs simultaneously by (for example magnetic stirring apparatus).Liquid phase precursor (liquid prephase) (for example 10kg) is joined aqueous phase, and the limit edged stirs (for example using magnetic stirring apparatus).Thus obtained preparation can further dilute or mix.

The vitamin A palmitate emulsifiable paste

Dispersion liquid will be by containing mixed with water acquisition of transparent phase precursor of following compositions:

Transparent phase precursor

Vitamin A palmitate (1.7x106IU/g) 0.45%

Compd A O7 0.45%

Soybean lecithin 1.73%

Miglyol812 3.00％

Polysorbate 80 3.40%

Ethanol 1.42%

Water:

The 10mm phosphate buffer, pH6 adds to 100.00%

Final preparation contains:

Spermol 10.00%

Hydrogenated groundnut 20.00%

Polysorbate 60 5.00%

Propylene glycol 20.00%

Phenyl phenol 0.50%

Above shown in dispersion liquid 23.00%

Purified water adds to 100.00%

When being replaced by AO3, AO4 or AO5, compd A O7 also obtains good result.

The Solcoseryl0.5% hydrogel

Dispersion liquid obtains by the transparent phase precursor and the water that will contain following compositions:

Transparent phase precursor

Solcoseryl 1.00％

Compd A O7 1.00%

Soybean lecithin 1.73%

Polysorbate 80 3.40%

Miglyol812 3.45％

Ethanol 1.42%

Water:

The 10mm phosphate buffer, pH6 adds to 100.00%

Final preparation contains:

Sodium carboxymethyl cellulose 450cP 3.50%

Above shown in dispersion liquid 50.00%

Purified water adds to 100.00%

Said preparation makes us feeling nice and cool and has good antiinflammation.

Skin protection W/O lotion

Dispersion liquid will be by containing the transparent phase precursor acquisition mixed with water of following compositions:

Transparent phase precursor

Alpha-tocopherol acetate 2.00%

Compd A O3 1.00%

Soybean lecithin 0.49%

Polysorbate 80 1.86%

Miglyol812 0.71％

Ethanol 0.63%

Water:

Purified water adds to 100.00%

Final preparation contains:

Glycerol sorbitan fatty ester 2.0%

Polyethoxy fatty acid ester 2.0%

Isostearic acid isopropyl ester 5.0%

Mineral oil 7.0%

Isopropyl palmitate 4.0%

Wheat germ oil 3.0%

Propylene glycol 3.8%

Above shown in dispersion liquid 5.0%

MgSO ₄x7H ₂O 0.7％

Spice 0.5%

Antiseptic, water

When being replaced by AO7, AO6 or AO8, compd A O3 also obtains good result.

UV defence day cream (O/W)

Dispersion liquid will be by containing the transparent phase precursor acquisition mixed with water of following compositions:

Parsol?MCX 2.59％

(octyl methoxycinnamate)

Parsol5000 1.11％

(4-UVINUL MBC95)

Compd A O7 1.00%

Miglyol812 1.30％

Soybean lecithin 0.50%

Polysorbate 80 3.40%

Ethanol 1.10%

Water:

Purified water adds to 100.00%

Final preparation contains:

PEG-5 glyceryl stearate 5.0%

Stearyl polyoxyethylene (21) ether 2.0%

Mineral oil 30.0%

Spermol 2.0%

Microwax 1.0%

Propylene glycol 6.0%

Above shown in dispersion liquid 10.0%

Water adds to 100.0%

Phenyl phenol+methyl parahydroxybenzoate,

Ethylparaben,

Propyl p-hydroxybenzoate,

Butyl p-hydroxybenzoate 0.3%

Claims (7)

1. pharmaceutical composition, it comprises following at least a chemical compound or mixture, and pharmaceutically suitable carrier

(9) mixture of following formula: compound:

(34) mixture of monoglyceride, diglyceride and the triglyceride of β-(3,5-di-t-butyl-4-hydroxyphenyl) propanoic acid and fatty acid.

2. according to the pharmaceutical composition of claim 1, wherein the total amount of chemical compound (9), (29)-(31) and (34) accounts for the 0.001-10% weight of whole compositionss.

3. according to the pharmaceutical composition of claim 1, be used for the treatment of skin injury or inflammatory or allergic conditions that free radical brings out.

4. the pharmaceutical composition of claim 1 is used for the purposes of topical therapeutic or the physically impaired medicine that brings out of prevention free radical in preparation.

5. the chemical compound (9), (29)-(31) of definition and (34) are used for preparing treatment or prevent skin injury that free radical brings out or the purposes of the medicine of inflammatory or allergic conditions in the claim 1.

6. the pharmaceutical composition of claim 1, it also comprises at least a material that is selected from antiinflammatory, vitamin, antipsoriatic, cell proliferation regulator, antiallergic agent, UV protective agent, humidizer, age resister and the DNA protective agent.

7. the method for pharmaceutical compositions, this method comprise will pharmaceutically active compound (9), (29)-(31) and (34) adding pharmaceutically suitable carrier of definition in the claim 1 of effective dose in.