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Differences and usage of "Cispera" hydroquinone, which can be expected to be effective for spots ...




Seiko Ko
Dr. Seiko Ko


Plastic surgeon Japan Plastic Surgery Society Japan Laser Medical Association (Councilor) Japan Cosmetic Surgery Society Japan Society of Aesthetic Dermatology Japanese Breast Oncoplastic Surgery Society Japanese Society of Anti-Aging Medicine


Medical institutions with Dr. Huang Seong-ko

Contact: 045-651-1117

Cyspera® is a cream used in cases of 30 melasma patients at the 2013 Annual Meeting of the American Academy of Dermatology Association (AAD).

Applying the cream once a day for 16 weeks will lead to brighter, healthier looking skin . However, in order to use Sispera effectively and safely, it is necessary to familiarize yourself with its prescribed usage.

Also, in order to choose the method that suits you, it is safe to know the difference from others. There are several types of ingredients that claim to have a whitening effect.

Differences and usage of "Cispera" hydroquinone, which can be expected to be effective for spots and melasma

Cispera is a cream containing cysteamine.

Cispera contains a variety of ingredients, but the most notable is cysteamine.

Cysteamine In 1966, Dr. Chavin's research team discovered that injections of cysteamine into black goldfish bleached them white . Furthermore, in 1968, the research team of Dr. Pathak and Dr. Bleehen showed that it was more effective than hydroquinone.

Background of commercialization of cream containing cysteamine

Thus, the reason why cysteamine has not been commercialized in the past, although its effects have been confirmed, is that cysteamine has a pungent odor, making it difficult to commercialize it as a topical agent for the skin. increase.

However, in 2012, Scientis developed a new technology to stabilize the ingredients as an external agent and strongly reduce the odor . As a result, Cispera, which contains 5% cysteamine, was commercialized as a cream .

Since cysteamine is also used as a component of hair perm solution, Cispera has a unique smell, as it is sometimes described as "smell like perm solution".

Hair is made of keratin, a type of protein, which is bound in various forms such as cystine bonds, ionic bonds, and hydrogen bonds. By combining again, it is wavy and straight. Cysteamine is included in 1 liquid that reduces "cysteine bond" among various bonds of keratin.

Knowing that Sispera contains the same ingredients as the perm solution, some people may feel reluctant to apply it to their skin, but it has been shown to be effective overseas, and in Singapore, South Korea, Malaysia, Taiwan, etc. It is widely used as a cosmetic not only in Asian countries, but also in the United States and Europe.

Cysteamine that suppresses the action of active oxygen

Cysteamine acts as an antioxidant that suppresses the action of active oxygen in the body .

Various substances, including antioxidants, are made up of molecules. Molecules are the smallest units that have the properties of matter, and are made up of combinations of atoms. Of these, active oxygen is an atom or molecule with an odd number of electrons.

At the center of an atom, there is a nucleus with two pairs of electrons, but some have an odd number of electrons, such as active oxygen.

Active oxygen is unstable because its electrons are not paired, and tries to be stable by stealing (oxidizing) electrons from others. On the other hand, antioxidants, which work as "reduction", which is the opposite of oxidation, give electrons to active oxygen to neutralize its oxidative power and prevent oxidation.

Active oxygen is generated when oxygen is taken into the body, and protects the body from harmful substances such as bacteria. As a result, symptoms such as spots, wrinkles, and sagging will appear.

Therefore, if the function of reactive oxygen that is excessively generated by antioxidants is suppressed, it can be expected to prevent the symptoms of spots, wrinkles, and sagging .

Who Sispera is suitable for

  • Those who are concerned about spots and freckles caused by sunburn
  • Those who are concerned about pigmentation such as acne scars
  • Those who are concerned about dullness or pigmentation on the lips
  • Those who want to manage pigmentation around the eyes
  • Those who are concerned about dark spots on the body

Sites where Sispera can be used

Sispera can be used on any body part, not just the face. Depending on the skin condition, irritation may occur more easily, so the application time may be shortened according to the doctor's advice.

  • Face (around eyes, including lips)
  • neck
  • the back of the hand
  • side
  • elbow
  • knees
  • Areola
  • ass
  • delicate zone

The difference between cispera and hydroquinone

Hydroquinone is known to suppress the action of the enzyme "tyrosinase" that produces melanin pigment, and creams containing hydroquinone are often used in combination with spot treatments such as lasers.

Cysteamine contained in Cispera also has the same effect as hydroquinone, which inhibits tyrosinase that produces melanin pigment, but we will check what is different.

Hydroquinone has precautions for use.

If you use hydroquinone cream for a long time , there is a risk of vitiligo where part of the skin becomes white, and when exposed to ultraviolet rays, spots become darker .

On the other hand, Cispera is said to have no risk from long-term use as the skin gradually gets used to it even if you feel irritation immediately after starting.

In addition, during the period of use of Sispera, it is recommended to take measures against ultraviolet rays when going out so that the effect can be felt more effectively, but there is no chemical change due to light such as "darkening of dark spots" (photosensitivity / photosensitivity). No), so you can use it at any time of the day, morning, noon or night.

Precautions when using hydroquinone

May have side effects
Hydroquinone is an ingredient that is also called a “skin bleaching agent” and is said to be effective in lightening and preventing dark spots. It is also characterized by allergic reactions such as redness, rashes, itching, and rough skin.
Since it has low skin permeability when used alone, it is often used in combination with tretinoin, which speeds up the skin's metabolism, ie, "turnover," and removes dead skin cells. Since the use of tretinoin involves downtime such as peeling (exfoliation of old keratin), dryness, and redness, some people avoid the combination treatment of hydroquinone and tretinoin because it does not suit their skin.
at risk of vitiligo
If used for a long time, the effect will be difficult to show, and the risk of vitiligo will increase.
Dark spots may occur
Spots on areas where hydroquinone cream has been applied may darken when exposed to ultraviolet light, so refrain from using it before going out.

Sispera can be used by people with hydroquinone allergies.

Sispera does not cause allergic reactions like hydroquinone cream, so it can be used by the following people.

  • Those who are allergic to hydroquinone
  • Those who are concerned about the downtime of treatment methods that combine tretinoin and hydroquinone

Sispera is a cream to be used at the doctor's discretion

Long-term use of high concentrations of hydroquinone increases the risk of vitiligo, so a doctor's prescription is required to purchase it, but low concentrations can be purchased as cosmetics on your own.

On the other hand, Sispera is a cream that is used when a doctor examines it and determines that it is necessary, and it is the doctor's responsibility to handle it.

How to use Sispera in two steps

The use of Sispera is divided into two phases.

  • Phase 1 (intensive care): once daily for 16 weeks
  • Stage 2 (maintenance treatment): 2 days a week, once a day

It begins with 16 weeks of intensive treatment, followed by maintenance treatment with Cispera twice a week to promote healthy skin.

It can be used at any time of the day, morning, noon, or night, but it is said that you will feel the effects more quickly if you use it at night when turnover occurs.

It is recommended to keep your skin well moisturized while using Sispera, and to use a sunscreen with a high SPF value such as SPF50 during the day.

How to use Sispella once a day

Give your skin a rest before applying Sispera

Since Sispera has a high penetrating power, it is desirable to apply it to the skin where some sebum remains . If you use it on dry skin after washing your face, it is likely to cause irritation such as strong redness and rashes, so if you use it after washing your face, wait at least one hour before applying.

There is no problem even if you moisturize with lotion etc. while you wait. Rather, using Cispera after moisturizing can reduce the irritation caused by dry skin.

Wait 15 minutes after applying Sispera

The amount of one use is 2 to 4 pushes, apply it all over and wait for 15 minutes. Redness and irritation may occur if left on without rinsing for longer than 15 minutes.

wash away

After washing with facial cleanser, rinse with lukewarm water.


Moisturize well after washing your face.

Things to know before using Sispera

Irritation after applying Sispera gradually disappears

As a side effect, a tingling sensation, a burning sensation, and redness may occur, but it will subside by rinsing it off and letting it sit for a while.

Such a reaction is normal, and although it may continue for several days from the day you start applying Sispera, it is said that the irritation will disappear as the skin gradually gets used to it. However, if there is no improvement after a few days, please consult a medical institution.

Sisperella is stored at 15°C to 30°C.

Cisperella should be stored at room temperature between 15°C and 30°C.

In addition, Sispera has the property of oxidizing and turning brown when exposed to air, so if there is oxidized cream on it, it must be removed before use.

The Sispera container is sealed in a vacuum state. Since the contents are pushed out with a pump, the cream in the container does not come into contact with air.

Concomitant use of Sispera with other cosmetic treatments

It is recommended to refrain from using Cispera during downtime after undergoing a peeling procedure to remove dead skin cells or after receiving cosmetic treatment.

Those who cannot use Sispera

  • Those with sensitive skin
  • Those undergoing peeling treatment
  • Those with peeling or redness
  • Those who are pregnant or breastfeeding, children under the age of 15 (children) for reasons that have not been tested
  • Those using retinol or tretinoin

Retinol is vitamin A. Tretinoin is a modified form of retinol, and is approved by the FDA (US Food and Drug Administration), which is the Ministry of Health, Labor and Welfare of Japan, as a drug used to treat skin spots, wrinkles, and acne. May increase irritation when used with Sispera .

Reference: Tretinoin

Points to note when purchasing Sispera

Sispera can be purchased at medical institutions and medical institution management sites, and it costs 35,200 yen (tax included) for a 50g capacity.

In addition, the Ministry of Health, Labor and Welfare has issued a warning regarding the purchase of creams for the purpose of whitening, so please use genuine products under the examination of a doctor.

"Please be careful about using foreign-made creams for the purpose of whitening that are personally imported via the Internet."

Treatment with KO CLINIC Sispera

We asked Dr. Huang, who supervised the article, about Sispella.

What kind of people does Dr. Huang recommend Sispella to?
Dr. Hwang Sung-ko
Normally, the goal is to improve the skin condition in one year by using whitening agents such as hydroquinone and lumixyl, as well as internal medicines such as tranexamic acid and vitamins C and E, and laser treatment. We are aiming to achieve about 80% in half a year, but there are some who cannot be expected to recover. Sispera is used for those who have difficulty recovering from normal treatment.
Will my skin return to normal if I stop using Cispera? What should I do to maintain the effect?
Dr. Hwang Sung-ko
Since Sispera assists in maintaining normal skin functions, we believe that stopping the use of Sispera will not worsen skin quality. In order to keep the skin healthy, UV protection and skin care (avoiding friction and moisturizing sufficiently) are essential. .
What are the benefits and risks of Cispera compared to tretinoin and hydroquinone?
Dr. Hwang Sung-ko
If the combination therapy of tretinoin and hydroquinone is overdone at the individual's discretion without adhering to the appropriate amount, there is a possibility that the metabolism of the skin will be accelerated too much and the necessary barrier function will be reduced. Cispera has a good peeling effect that is not as strong as retinol, so it tends to promote the excretion of melanin pigment while maintaining the barrier function.
Are there any precautions when using Sispera?
Dr. Hwang Sung-ko
Treatment at a medical institution is based on whether there is a living environment and habits that make it easy to be exposed to ultraviolet rays on a daily basis, the state of melanocytes that produce melanin pigment, and the state of melanin pigment that accumulates on the surface of the skin. Treatment is performed while determining whether is effective.

Therefore, it is not possible to say unequivocally that Cispera works for which symptoms. Depending on the skin condition, there may be cases where treatment with other methods other than Sispera is necessary. Alternatively, other treatments or existing topical agents may be sufficient.

Depending on the patient's condition, Cispera may work effectively when existing treatments do not improve pigmentation. Basically, we recommend that you use it after receiving a medical examination at a medical institution that specializes in cosmetic skin diagnosis.
Thank you Mr. Huang!

Medical personnel only content

Cysteamine, which inhibits the synthesis of melanin pigment

Cysteamine is a compound found in mammalian cells Cysteamine is a decomposition product formed when the essential amino acid "L-cysteine" is broken down in the body , and inhibits the synthesis of melanin pigment .

Among mammals, cysteamine is found in high concentrations in human breast milk and acts as an antioxidant.

Effect of cysteamine on the process of pigmentation

Confirmation of pigmentation process by melanin pigment

The skin is layered from the outside to the epidermis and dermis, but the epidermis is further divided into four layers. The melanin pigment that causes spots and chloasma is stored in bag-like organs called "melanosomes". Melanosomes are present in melanocytes, pigment cells in the basal layer, the lowest layer of the epidermis.

Melanosomes filled with melanin pigment are passed from melanocytes to skin cells "keratinocytes" by the action of proteins, etc., and if it is healthy skin, it will be pushed upwards by turnover. In the process, the melanosomes are digested, and the melanin pigment is eventually excreted from the body along with the old keratin.

However, if melanin pigment is overproduced due to melanocyte activation, or if the turnover cycle is disturbed due to the effects of ultraviolet rays or friction , melanin pigment becomes difficult to excrete from the body and accumulates, resulting in pigmentation . .

A melanin pigment produced by a chemical reaction of tyrosine

Antioxidants such as cysteamine contained in Cispera are known to affect the production pathway of melanin pigment.

When melanocytes are activated by stimulation such as ultraviolet rays, the following chemical reactions occur within melanosomes, producing melanin pigments.

  1. Tyrosine is oxidized by tyrosinase
  2. "Dopa" is produced (tyrosine hydroxylase activity)
  3. Dopa is oxidized by dopa oxidase, which is the action of tyrosinase, and "dopaquinone" is produced (dopa oxidase activity)
  4. "Dopaquinone" is oxidized and changed to "indolol compound"
  5. become melanin pigment

Action of cysteamine in melanogenesis pathway

The following 9 actions are effective in preventing the production of melanin pigment, and Cispera contains cysteamine and niacinamide, so it can be said that there are 5 actions.

Mechanism of action component
Tyrosinase inhibitor cysteamine, hydroquinone, succinic acid, arbutin, azelaic acid, ascorbic acid, ellagic acid, glycolic acid, EFG
dopa oxidase inhibitor cysteamine, mulberry extract
Peroxidase substrate inhibitor (protects against oxidative stress) Cysteamine
Increased intracellular glutathione Cysteamine
Inhibition of melanosome translocation Niacinamide, soybean extract, ipselen, durianic acid
anti-hormonal agent Flutamide
Improvement of stratum corneum turnover tretinoin, glycolic acid
Blocking the plasmin pathway Tranexamic acid
Cytotoxicity hydroquinone

Specifically, cysteamine is said to suppress the production of melanin pigment by the following actions .

  • Inhibition of tyrosine oxidation
  • Inhibits dopa production
  • Inhibition of conversion to indole compounds
  • Inhibition of the Fenton reaction* by quenching (quenching) of iron and copper ions (*active oxygen is generated when the Fenton reaction occurs)
  • Quenching of dopaquinone (removal of dopaquinone from the melanogenesis pathway)
  • Increases intracellular glutathione (antioxidant effect)
  • Reduces the dark melanin in the stratum corneum to a bright color with its antioxidant action.

The action of reducing the dark melanin in the stratum corneum to a bright color prevents the production of black melanin by acting as an antioxidant in two types of melanin pigments, black melanin (eumelanin) and yellow melanin (pheomelanin). means

In the process of oxidation of dopaquinone, which produces black melanin, bright yellow melanin is produced in the presence of antioxidant components.

Comparison of the difference between cysteamine and hydroquinone

In addition to tyrosinase inhibition , which is also the mechanism of action of hydroquinone, cysteamine has multiple actions that block the production of melanin pigment, such as inhibition of peroxidase and dopaquinone, increase of glutathione, and inhibition of reactions that generate active oxygen. I understand.

Cysteamine Hydroquinone
Origin of molecule human origin Chemical substances
Mechanism of action Tyrosinase inhibition, peroxidase inhibition, intracellular glutathione increase, dopaquinone reaction termination (quenching), Fenton-type reaction inhibition that generates active oxygen, melanin reduction in stratum corneum Tyrosinase inhibition
merit High bleaching effect, no photosensitivity, biocompatibility & acceptable degree of oxidation High bleaching effect
side effects Mild irritation (if not used as directed) rebound (worsening of pigmentation), photosensitivity, tissue browning, black spots, depigmentation
safety Non-cytotoxic, antimutagenic, anticarcinogenic, radioprotectant -

Hydroquinone has “depigmentation” as a side effect, and hydroquinone is highly irritating, so long-term use increases the risk of vitiligo .

It is also known to be a potentially mutagenic and carcinogenic compound and is known to induce tissue bronchosis.

Reference: Hydroquinone and its analogues in dermatology - a potential health risk
Reference: Exogenous ochronosis: the failure of depigmenting creams
Reference: Exogenous Ochronosis

In addition to cysteamine and hydroquinone, there are several ingredients that are said to affect the suppression of melanin pigment production. For example, there are non-hydroquinone topical agents such as tranexamic acid, kojic acid, arbutin, azelaic acid, retinoids, and hydroxy acids. It is said.

Cispera has few side effects

The following is based on daily use by 40 melasma patients (women and men aged 18 to 50 with skin color types "Fitzpatrick skin types III, IV, and V", which are common in Japan). Data.

do not have Mild Moderate severe
drying 80% 20% 0% 0%
Erythema 65% 20% 15% 0%
stimulation 80% 15% Five% 0%
itch 75% twenty five% 0% 0%
heat sensation 75% 15% Ten% 0%
bleaching 100% 0% 0% 0%

Reference: Farshi et al, 2018, JDT 29:2, 182-189

From the above data, it can be seen that although some people may feel moderate "erythema" and "heat sensation", there is no depigmentation of the skin color.

Treatment with Cisperella published overseas

Treatment with Sispera for 16 weeks overseas showed a 67% reduction in the melanin index of melasma lesions and a 58% reduction in melasma area . (Female and male patients aged 18-50 years with skin color type "Fitzpatrick skin type III, IV, and V" common in Japanese)

In addition to the AAD cases introduced at the beginning, results have been shown in multiple clinical evaluations.

Double-blind test results

In 2015, the British Journal of Dermatology (BJD) conducted the first double-blind study (double-blind test) targeting 50 patients with epidermal melasma, confirming its efficacy. I was.

Double-blind testing is a commonly used method to confirm the efficacy and therapeutic effects of drugs. The purpose is to confirm the true effect of the drug, and the clinical trial is conducted in a state where neither the treatment side nor the recipient side know which is the real drug.

Reference: Evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial

Comparison with other treatments that lighten spots

"Skin Research & Techonology" shows clinical results demonstrating superior efficacy and tolerability to the Kligman regimen in the treatment of 50 melasma patients.

Kligman's prescription is a whitening ointment "Kligman Ointment" (containing hydroquinone, tretinoin, and dexamethasone) jointly created by Dr. Kligman and Dr. Viral. I'm here.

Cispera can also be used if Kligman ointment is ineffective.

Reference: Clinical evaluation of efficacy, safety and tolerability of cysteamine 5% cream in comparison with modified Kligman's formula in subjects with epidermal melasma: A randomized, double-blind clinical trial study

In addition, the treatment results show that tranexamic acid, which is also used as an internal medicine and is used to treat age spots, has fewer complications and has the same effect as tranexamic acid mesotherapy , which is injected into the skin with a needle. It has been.

Reference: Clinical evaluation of efficacy and tolerability of cysteamine 5% cream in comparison with tranexamic acid mesotherapy in subjects with melasma: a single-blind, randomized clinical trial study

[Limited to medical professionals] We asked Dr. Huang about Sispella

Dr. Huang answered some frequently asked questions from doctors about Sispella.

In what cases do you use Sispella?
Dr. Hwang Sung-ko
I use Sispera for intractable cases.
We aim to achieve about 80% improvement in half a year by using IPL, laser toning, and pico laser treatment while using whitening agents along with UV protection and correct skin care. However, there are some cases in which melasma and pigmented spots remain and improvement of about 80% cannot be expected.

In such cases, melasma and pigmented spots are mixed and overlapped. It is necessary to protect the overstimulated melanocytes without stimulating them and to treat the pigmented spots, but these two treatments are contradictory, so it is difficult to perform them at the same time.

In that case, first of all, it is necessary to stabilize the melanocytes with topical and internal medicines, UV protection, and skin care.
I hear that it is not possible to use it in combination with retinol, but what is the actual situation?
Dr. Hwang Sung-ko
It's not a bad thing, but I don't use Cispera in combination with retinol because I'm using Cispera in cases where I have a delicate melanocyte condition that would be irritated by using retinol.
How is the effect on Japanese skin (skin type II to III)?
Dr. Hwang Sung-ko
I think it goes well with Japanese skin types II to III. As you can see from the fact that Japanese people, who are of yellow race, are more prone to pigmentation when they get sunburnt compared to Caucasians, their skin is naturally prone to stimulating melanocytes. Therefore, it is necessary to consider stimulation of melanocytes in treatment, but Cisperella has relatively little stimulation of melanocytes and tends to improve pigmentation by suppressing melanin production. I think it's good to adapt to.
How is Sispella incorporated into treatment? Is it always necessary to use it with a laser?
Dr. Hwang Sung-ko
If melanocytes are stimulated by laser treatment, treatment using devices such as lasers is not performed, and in some cases, conservative treatment, including cispella, is performed. The best way to protect melanocytes, which produce melanin pigment, is conservative therapy with topical medicines such as Cispera, internal medicines, UV protection, and skin care without laser treatment. The basic idea is that once melanocytes have stabilized through conservative therapy, laser therapy should be added for greater efficacy.
What do you think are the advantages and disadvantages of Syspera? (How should I use it to enhance the treatment effect of blemishes?)
Dr. Hwang Sung-ko
If you have strong pigmentation due to laser treatment, it is surprisingly common that the skin loses pigment at the same time and becomes mottled. At this time, the point is how to restore the lost areas while using whitening agents to restore the pigmentation.

Therefore, using Sispera restores the depigmented areas without exacerbating them, while also restoring pigmentation and making the skin tone uniform (conservative therapy and needle RF are also used). I like the fact that it can be used in cases that are difficult to adjust like this.

The disadvantage is the high cost. Therefore, we use hydroquinone and lumixil in cases that can be recovered.
Thank you Mr. Huang!

Introduction of supervising doctor

Dr. Seiko Kou, the director of KO CLINIC. As a leading expert in “customized treatment” that performs appropriate treatment based on analysis by diagnostic imaging equipment, he has presented at many academic conferences and lectures. Started clinical research on melasma in 2007, and currently instructs many doctors and medical professionals on treatment methods using multiple lasers. Established a treatment centered on skin care medicine aiming for healthy and beautiful skin. His major publications include “Your skin will change your life!” and many others.

Medical institutions with Dr. Huang Seong-ko

Contact: 045-651-1117